Lymphoma, Non-Hodgkin
Conditions
Keywords
Bexxar, Non-Hodgkin's Lymphoma, Tositumomab, Anti-B1 Antibody, Radioimmunotherapy, Iodine I-131, Iodine-131
Brief summary
Subjects were randomized to receive either tositumomab (Anti-B1 Antibody) and iodine I 131 tositumomab (Arm A) or unlabeled tositumomab (Arm B). Subjects randomized to Arm B were allowed to cross over and receive I 131 tositumomab once their disease had progressed as long as they still fulfilled the protocol entry criteria (except for exclusion criterion 12, prior monoclonal antibody therapy) and were human anti-murine antibody (HAMA) negative. Study endpoint assessments of response were conducted by a Masked Independent Randomized Radiographic and Oncologic Review (MIRROR) panel and the Study Investigators' assessments of safety and survival. Subjects who completed at least two years of follow-up in Protocol BEX104515 (formerly Corixa Protocol RIT-II-002) were enrolled in long term follow-up Protocol BEX104526 (formerly Corixa Protocol CCBX001-051), an administrative protocol, for continued radiographic response evaluations and safety evaluations every 6 months for years 3 through 5 post-treatment and annually for years 6 through 10 post-treatment. Subjects in BEX104526 were assessed for survival, disease status, subsequent therapy for NHL, and long-term safety, including the use of thyroid medication, development of hypothyroidism, human anti murine antibody (HAMA), myelodysplastic syndrome, acute myelogenous leukemia, and all other secondary malignancies. Additionally, subjects were followed for the development of any adverse event(s) deemed by the Principal Investigator as being possibly or probably related to a subject's previous treatment with Iodine I-131 tositumomab. Laboratory evaluations consisting of a thyroid stimulating hormone level and a complete blood cell count, with a differential and platelet count, were obtained annually through year 10 post-treatment. Dosimetric Dose: Subjects received 450 mg of tositumomab IV followed by 5.0 mCi of Iodine I-131 and 35 mg of tositumomab. Following the dosimetric dose, whole body dosimetry was performed on each subject using a total body gamma camera. Whole body anterior and posterior whole body images were obtained at the following timepoints. 1. Within one hour of infusion of the dosimetric dose and prior to urination 2. 2-4 days after infusion of the dosimetric dose, following urination 3. 6-7 days after infusion of the dosimetric dose, following urination Therapeutic Dose: The total body residence time, derived from total body gamma camera counts obtained at the 3 time points, was used to calculate the iodine-131 activity (mCi) to be administered to deliver the therapeutic total body irradiation dose of 65 or 75 cGy. The therapeutic step was administered 7-14 days after the dosimetric step and consisted of tositumomab 450 mg followed by an activity (mCi) of iodine-131 calculated to deliver 75 cGy or 65 cGy of total body irradiation, depending on platelet count, and 35 mg of tositumomab. For subjects with ≥150,000 platelets/mm3, the recommended dose was the activity of iodine-131 calculated to deliver 75 cGy of total body irradiation; for subjects with NCI Grade 1 thrombocytopenia (platelet counts ≥100,000 but \<150,000 platelets/mm3), the recommended dose was the activity of iodine-131 calculated to deliver 65 cGy of total body irradiation.
Detailed description
This is a Phase II randomized, controlled, two-arm, open-label, multicenter study comparing the safety and efficacy of tositumomab and iodine I 131 tositumomab to tositumomab for the treatment of chemotherapy-relapsed or refractory low-grade or transformed low-grade B-cell NHL. Treatment Arm A: Subject will undergo 2 phases of study. In the first phase, termed dosimetric dose, subjects will receive tositumomab (450 mg) followed by tositumomab (35 mg) that has been trace labeled with 5mCi) Iodine-131 tositumomab. Whole body gamma camera scans will be obtained on day 0, day 2, 3, or 4, and day 6 or 7 following the dosimetric dose. Using the dosimetric data from three imaging time points, a subject-specific dose of iodine I 131 tositumomab to deliver the desired total body dose of radiotherapy will be calculated. In the second phase of the study, termed therapeutic dose, subjects will receive unlabeled tositumomab (450mg) followed by iodine tositumomab (35mg) labeled with the subject-specific dose of iodine I-131 to deliver a whole body dose of 75 cGy to subjects. Subjects with platelet counts of 100,001 - 149,999 cells/mm3, will receive 65 cGy and subjects who are obese will be doses based on 137% of their lean body mass. Subjects will be treated with either saturated solution potassium iodide (SSKI), Lugol's solution, or potassium iodide tablets starting at least 24 hours prior to the first infusion of the Iodine-131 tositumomab (i.e., the dosimetric dose) and continuing for 14 days following the last infusion of radiolabeled tositumomab (i.e., the therapeutic dose). Treatment Arm B: Subjects will receive the same amount of unlabeled tositumomab (450 + 35 mg) administered over the same time-frame as Arm A on the study Days 0 and 7 (the day 7 dose may be delayed but no longer than 14 days after the first dose). Crossover treatment Arm B: Subjects in Arm B may crossover and receive Iodine-131 tositumomab following progression of their lymphoma if they still fulfill the protocol inclusion exclusion criteria (except exclusion criteria#12) and are HAMA-negative.
Interventions
BIOLOGICALIodine-131 Anti-B1 Antibody Versus Anti-B1 Antibody in Chemotherapy-Relapsed/Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin's Lymphoma (NHL)
Subjects will be randomized to receive tositumomab and iodine-131 tositumomab (Arm A) or unlabeled tositumomab (Arm B). Subjects randomized to receive unlabeled tositumomab may crossover and receive radiolabeled Iodine-131 tositumomab following progression of their lymphoma. Response in both arms will be assessed at 7 weeks, 13 weeks, and then at 3-monthly intervals for up to 2 years.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed low-grade or transformed NHL with evaluable, measurable disease * Tumor had to express CD20 antigen * One to three prior chemotherapy regimens * Karnofsky performance score ≥60% and anticipated survival ≥3 months * Absolute neutrophil count (ANC) \>1500/mm3 and platelet count \>100,000/mm3 * Adequate renal and hepatic function * 18 years of age or older. * Written informed consent and sign an IRB-approved Informed consent from prior to study entry.
Exclusion criteria
* More than an average of 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically within 42 days of study entry. Bilateral posterior iliac crest core biopsies are required if the percentage of intratrabecular space involved exceeds 10% on a unilateral biopsy. The mean of bilateral biopsies must be no more than 25%. * Received cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within FOUR weeks prior to study entry (6 weeks of nitrosourea compounds) or who exhibit persistent clinical evidence of toxicity. The use of steroids must be discontinued at least 1 week prior to study entry. * Have undergone prior stem cell transplant. * Active obstructive hydronephrosis. * Evidence of active infection requiring intravenous antibiotics at the time of study entry. * New York Heart Association class III or IV heart disease or other serious illness that would preclude evaluation. * Prior malignancy other than lymphoma, except for adequately-treated skin cancer, in situ cervical cancer, or other cancer for which subject has been disease-free for 5 years. * Known HIV infection. * Known brain or leptomeningeal metastases. * Pregnant or nursing. Subjects of childbearing potential must undergo pregnancy test within 7 days of study entry and antibody is not to be administered until a negative result is obtained. For those subjects in Arm B, the pregnancy test must be repeated within 7 days of crossover. Male and female must agree to use effective contraception for 6 months following the therapeutic dose, as applicable. * Previous allergic reactions to iodine. This does not include reactions to intravenous iodine-containing contrast materials. * Previously given any monoclonal or polyclonal antibodies of any non-human species for either diagnostic or therapeutic purpose. This includes engineered chimeric and humanized antibodies. * Previously received radioimmunotherapy . * Progressive disease within one year of irradiation arising in a field that has been previously irradiated with \>3500 cGy. * de novo intermediate or high-grade lymphoma. * Received \>3 chemotherapy regimens (different or identical agents).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions). |
| Number of Participants With Confirmed Response Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Participants receiving Unlabeled TST with progressive disease (defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measureable lesions or the appearance of any new lesion. Individual lesions must be \>2 centimeters \[cm\] in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.) were assessed separately before and after receiving the crossover treatment of I 131 TST for confirmed response, which included participants with CR, CCR, and PR. |
| Number of Participants With Confirmed Complete Response (CR) as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | CR is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. |
| Number of Participants (Par.) With a Confirmed Complete Response as Assessed by the Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel | The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001 | Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions). |
| Number of Participants With Confirmed Complete Response (CR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST for CR. CR is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. |
| Number of Participants With Confirmed Clinical Complete Response (CCR) as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | CCR is defined as the complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion =\<2 cm in diameter by radiographic evaluation or =\<1 cm in diameter by physical examination can be considered scar tissue. |
| Number of Participants With Confirmed Clinical Complete Response (CCR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST for CCR. CCR is defined as the complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion =\<2 cm in diameter by radiographic evaluation or =\<1 cm in diameter by physical examination can be considered scar tissue. |
| Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | CCR is defined as the complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion =\<2 cm in diameter by radiographic evaluation or =\<1 cm in diameter by physical examination can be considered scar tissue. The extent of disease must be unchanged or decreased upon follow-up evaluations. If the extent of disease was unchanged or if further decreases occurred for 6 months or longer, the participant was reclassified as having a CR. |
| Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST for CR + CCR. |
| Number of Participants With Confirmed Partial Response (PR) as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Confirmed PR is defined as a \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions. |
| Number of Participants With Confirmed Partial Response (PR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST confirmed PR. Confirmed PR is defined as a \>=50 percent reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (Par.) With a Confirmed Response (CR, CCR, or PR) as Assessed by the MIRROR Panel | The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001 | Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions). |
| Duration of Response for All Confirmed Responders, Confirmed Complete Responders, and Confirmed Partial Responders | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | For all participants with CR, CCR, or PR, duration of response was defined as the time from first documented response to first documented progression. All confirmed responders included participants with CR, CCR, and PR, whereas confirmed complete responders included participants with CR and CCR. |
| MIRROR Panel Assessments of Duration of Complete Response (Time From the First Documented Response to the First Documented Progression) | The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001 | Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions). |
| MIRROR Panel Assessments of Duration of Confirmed Response (Time From the First Documented Response to the First Documented Progression) | The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001 | Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions). |
| Time to Progression of Disease or Death as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Progression-free survival or time to progression is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death. |
| Time to Progression of Disease or Death in Participants Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Progression-free survival or time to progression is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death. |
| MIRROR Panel Assessed Time to Response (Time From the Date of Enrollment to the First Documented Response (PR, CR, CCR) | The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001 | Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions). |
| MIRROR Panel Assessed Progression-free Survival | The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001 | Time from the date of enrollment (the date of randomization) to the first documented progression or death. |
| Overall Survival | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Overall survival is defined as the time from the treatment start date to the date of death by any cause. |
| Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Causality of AEs was determined by the investigators as none, remote, possible, probable, or highly probable. AEs considered by the investigator as being at least remotely related to the study treatment were considered to be DR AEs. White blood cell (WBC) count and absolute neutrophil count (ANC) were measured as cells per millimeters cubed (mm\^3); hemoglobin was measured in grams per deciliter (g/dL). |
| Number of Participants With the Indicated Type of Infection | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Specimen samples of the body fluid are cultured for testing whether the infectious organism is present and grown in the culture media to assess the growth pattern of the organisms present in the specimen. The culture results could be positive or negative. The positive culture results indicate that the tested participant has the infection under investigation, in which case therapeutic treatment with anti-infective is required. |
| Number of Participants With an Infection for Which Anti-infectives Were Administered | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Anti-infectives are capable of acting against infection, by inhibiting the spread of an infectious agent or by killing the infectious agent outright. Anti-infective is a general term that encompasses antibacterials, antibiotics, antifungals, antiprotozoans, and antivirals. |
| Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event. |
| Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event. |
| Number of Participants With the Indicated Primary Cause of Death | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Participants were categorized according to their primary cause of death. Deaths due to progressive disease or to another reason (Other) were not captured as serious adverse events (SAEs) and are thus not included in the SAE module. |
| Number of Participants With a Time to Death From the Last Dose of Study Drug Less Than or Equal to 30 Days or More Than 30 Days | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Time to death from the last dose of study drug is the time from the last dose of study drug administered to the date of death. Deaths due to progressive disease or to another reason (Other) were not captured as serious adverse events (SAEs) and are thus not included in the SAE module. |
| Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life-threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the investigator's medical judgement. |
| Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life-threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the investigator's medical judgement. |
| Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Nadir is defined as the lowest laboratory value recorded following the administration of the study medication. Time to recovery to baseline in hematologic laboratory evaluations is the time required for recovery from nadir values to baseline values. Hematologic laboratory evaluations included ANC, hemoglobin (Hb), platelets (Plt), and WBC count. |
| Nadir Values for ANC, a Hematologic Parameter | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Nadir is defined as the lowest laboratory value recorded following the administration of study medication. ANC is a measure of the number of neutrophil granulocytes present in the blood. Neutrophils are a type of white blood cell that fights against infection. |
| Nadir Values for Hemoglobin, a Hematologic Parameter | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells. |
| Nadir Values for the Hematologic Parameters Platelets and WBC Count | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Platelets and WBCs are types of blood cells. |
| Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event. |
| Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event. |
| Time to Human Anti-Murine Antibodies (HAMA) Positivity From the First Dosimetric Dose | Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. | Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants in this study were evaluated to determine whether they developed an immune response to study treatment as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I 131 tositumomab. A positive HAMA value indicates that the participant developed human anti-mouse antibodies above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of human anti-mouse antibodies. |
Participant flow
Pre-assignment details
Participants (par.) received radioimmunotherapy of tositumomab (TST)/Iodine I 131 TST (Arm A) or unlabeled TST (Arm B) in 2 phases: dosimetric and therapeutic dose. Arm B par. were allowed to crossover and receive I 131 TST, if disease progressed. After TST treatment, par. could have entered a Long-Term Follow-Up study (BEX104526; NCT00240591).
Participants by arm
| Arm | Count |
|---|---|
| TST and Iodine I 131 TST Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray \[cGy\] or 65 cGy) and 35 mg of TST IV, was administered 7-14 days after the DD. Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study. | 42 |
| Unlabeled TST Participants received a DD consisting of 450 mg and 35 mg of unlabelled TST IV. The TD consisting of 450 mg and 35 mg of TST IV was administered 7-14 days after the DD. Participants randomized to receive 450 mg and 35 mg of unlabelled TST IV during the DD and TD phase were allowed to crossover and receive I 131 TST using the same regimen used in the TST and Iodine I 131 TST treatment arm once their disease had progressed as long as they still fulfilled the protocol entry criteria. Participants who had completed at least 2 years of follow-up after administration of TST during the TD phase and had signed the informed consent to participate in the LTFU study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study. | 36 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Crossover Phase | Death | 0 | 3 |
| Crossover Phase | Lack of Efficacy | 0 | 13 |
| Crossover Phase | Lost to Follow-up | 0 | 2 |
| Dosimetric and Therapeutic Treatment | Death | 0 | 1 |
| Dosimetric and Therapeutic Treatment | Lack of Efficacy | 27 | 32 |
| Dosimetric and Therapeutic Treatment | Lost to Follow-up | 4 | 2 |
| Dosimetric and Therapeutic Treatment | Received Other Treatment | 2 | 0 |
| Dosimetric and Therapeutic Treatment | Withdrawal by Subject | 2 | 0 |
| Long-Term Follow-Up | Death | 3 | 0 |
| Long-Term Follow-Up | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | TST and Iodine I 131 TST | Unlabeled TST | Total |
|---|---|---|---|
| Age, Continuous | 56.3 Years STANDARD_DEVIATION 11.6 | 55.4 Years STANDARD_DEVIATION 12.8 | 55.8 Years STANDARD_DEVIATION 12.1 |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Other/Unknown | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 39 participants | 33 participants | 72 participants |
| Sex/Gender, Customized Female | 19 Participants | 18 Participants | 37 Participants |
| Sex/Gender, Customized Male | 23 Participants | 18 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 42 / 42 | 33 / 36 | 19 / 19 |
| serious Total, serious adverse events | 18 / 42 | 6 / 36 | 10 / 19 |
Outcome results
Primary
Number of Participants (Par.) With a Confirmed Complete Response as Assessed by the Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel
Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).
Time frame: The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001
Population: ITT-Exposed Population. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants (Par.) With a Confirmed Complete Response as Assessed by the Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel | 14 participants |
| Unlabeled TST | Number of Participants (Par.) With a Confirmed Complete Response as Assessed by the Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel | 3 participants |
p-value: 0.012Fisher Exact
Primary
Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator
Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: Intent-to-Treat (ITT) Exposed Population: all participants who were enrolled into the study and received at least one dose of study drug. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator | 21 participants |
| Unlabeled TST | Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator | 8 participants |
95% CI: [35, 65]
95% CI: [9, 36]
Primary
Number of Participants With Confirmed Clinical Complete Response (CCR) as Assessed by the Investigator
CCR is defined as the complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion =\<2 cm in diameter by radiographic evaluation or =\<1 cm in diameter by physical examination can be considered scar tissue.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With Confirmed Clinical Complete Response (CCR) as Assessed by the Investigator | 1 participants |
| Unlabeled TST | Number of Participants With Confirmed Clinical Complete Response (CCR) as Assessed by the Investigator | 1 participants |
95% CI: [0, 7]
95% CI: [0, 8]
Primary
Number of Participants With Confirmed Clinical Complete Response (CCR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator
Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST for CCR. CCR is defined as the complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion =\<2 cm in diameter by radiographic evaluation or =\<1 cm in diameter by physical examination can be considered scar tissue.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants receiving Unlabeled TST who received the crossover treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With Confirmed Clinical Complete Response (CCR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 0 participants |
| Unlabeled TST | Number of Participants With Confirmed Clinical Complete Response (CCR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 1 participants |
95% CI: [0, 0]
95% CI: [0, 15]
Primary
Number of Participants With Confirmed Complete Response (CR) as Assessed by the Investigator
CR is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With Confirmed Complete Response (CR) as Assessed by the Investigator | 11 participants |
| Unlabeled TST | Number of Participants With Confirmed Complete Response (CR) as Assessed by the Investigator | 3 participants |
95% CI: [13, 39]
95% CI: [0, 17]
Primary
Number of Participants With Confirmed Complete Response (CR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator
Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST for CR. CR is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants receiving Unlabeled TST who received the crossover treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With Confirmed Complete Response (CR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 0 participants |
| Unlabeled TST | Number of Participants With Confirmed Complete Response (CR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 8 participants |
95% CI: [0, 0]
95% CI: [20, 64]
Primary
Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) as Assessed by the Investigator
CCR is defined as the complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion =\<2 cm in diameter by radiographic evaluation or =\<1 cm in diameter by physical examination can be considered scar tissue. The extent of disease must be unchanged or decreased upon follow-up evaluations. If the extent of disease was unchanged or if further decreases occurred for 6 months or longer, the participant was reclassified as having a CR.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) as Assessed by the Investigator | 13 participants |
| Unlabeled TST | Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) as Assessed by the Investigator | 4 participants |
95% CI: [17, 45]
95% CI: [1, 21]
Primary
Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator
Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST for CR + CCR.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants receiving Unlabeled TST who received the crossover treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 0 participants |
| Unlabeled TST | Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 9 participants |
95% CI: [0, 0]
95% CI: [25, 70]
Primary
Number of Participants With Confirmed Partial Response (PR) as Assessed by the Investigator
Confirmed PR is defined as a \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With Confirmed Partial Response (PR) as Assessed by the Investigator | 7 participants |
| Unlabeled TST | Number of Participants With Confirmed Partial Response (PR) as Assessed by the Investigator | 4 participants |
95% CI: [5, 28]
95% CI: [1, 21]
Primary
Number of Participants With Confirmed Partial Response (PR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator
Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST confirmed PR. Confirmed PR is defined as a \>=50 percent reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants receiving Unlabeled TST who received the crossover treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With Confirmed Partial Response (PR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 3 participants |
| Unlabeled TST | Number of Participants With Confirmed Partial Response (PR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 6 participants |
95% CI: [0, 32]
95% CI: [11, 52]
Primary
Number of Participants With Confirmed Response Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator
Participants receiving Unlabeled TST with progressive disease (defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measureable lesions or the appearance of any new lesion. Individual lesions must be \>2 centimeters \[cm\] in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.) were assessed separately before and after receiving the crossover treatment of I 131 TST for confirmed response, which included participants with CR, CCR, and PR.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants receiving Unlabeled TST who received the crossover treatment were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With Confirmed Response Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 3 participants |
| Unlabeled TST | Number of Participants With Confirmed Response Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 15 participants |
95% CI: [0, 32]
95% CI: [61, 97]
Secondary
Duration of Response for All Confirmed Responders, Confirmed Complete Responders, and Confirmed Partial Responders
For all participants with CR, CCR, or PR, duration of response was defined as the time from first documented response to first documented progression. All confirmed responders included participants with CR, CCR, and PR, whereas confirmed complete responders included participants with CR and CCR.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. Only those participants evaluable for CR, CCR, or PR were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TST and Iodine I 131 TST | Duration of Response for All Confirmed Responders, Confirmed Complete Responders, and Confirmed Partial Responders | All Confirmed Responders, n=21, 8 | 42.0 months |
| TST and Iodine I 131 TST | Duration of Response for All Confirmed Responders, Confirmed Complete Responders, and Confirmed Partial Responders | Confirmed Complete Responders, n=13, 4 | 116.8 months |
| TST and Iodine I 131 TST | Duration of Response for All Confirmed Responders, Confirmed Complete Responders, and Confirmed Partial Responders | Confirmed PR, n=7, 4 | 4.6 months |
| Unlabeled TST | Duration of Response for All Confirmed Responders, Confirmed Complete Responders, and Confirmed Partial Responders | All Confirmed Responders, n=21, 8 | 18.5 months |
| Unlabeled TST | Duration of Response for All Confirmed Responders, Confirmed Complete Responders, and Confirmed Partial Responders | Confirmed Complete Responders, n=13, 4 | NA months |
| Unlabeled TST | Duration of Response for All Confirmed Responders, Confirmed Complete Responders, and Confirmed Partial Responders | Confirmed PR, n=7, 4 | 6.2 months |
Secondary
Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities
Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants with Grade 3 or Grade 4 hematologic toxicities were analyzed. The n in the category titles reflects the number of participants with the indicated Grade 3 or Grade 4 hematologic toxicity.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TST and Iodine I 131 TST | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | ANC, n=14, 4, 11 | 15 days |
| TST and Iodine I 131 TST | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Hemoglobin, n=6, 0, 3 | 16 days |
| TST and Iodine I 131 TST | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Platelets, n=15, 1, 9 | 22 days |
| TST and Iodine I 131 TST | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | WBC count, n=18, 4, 11 | 20 days |
| Unlabeled TST | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | WBC count, n=18, 4, 11 | 22 days |
| Unlabeled TST | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | ANC, n=14, 4, 11 | 24 days |
| Unlabeled TST | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Platelets, n=15, 1, 9 | 411 days |
| Unlabeled TST | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Hemoglobin, n=6, 0, 3 | NA days |
| Unlabeled TST Crossover | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | WBC count, n=18, 4, 11 | 30 days |
| Unlabeled TST Crossover | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Hemoglobin, n=6, 0, 3 | 42 days |
| Unlabeled TST Crossover | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Platelets, n=15, 1, 9 | 41 days |
| Unlabeled TST Crossover | Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities | ANC, n=14, 4, 11 | 16 days |
Secondary
MIRROR Panel Assessed Progression-free Survival
Time from the date of enrollment (the date of randomization) to the first documented progression or death.
Time frame: The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001
Population: ITT-Exposed Population. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST | MIRROR Panel Assessed Progression-free Survival | 6.3 months |
| Unlabeled TST | MIRROR Panel Assessed Progression-free Survival | 5.5 months |
p-value: 0.016Log Rank
Secondary
MIRROR Panel Assessed Time to Response (Time From the Date of Enrollment to the First Documented Response (PR, CR, CCR)
Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).
Time frame: The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001
Population: ITT-Exposed Population. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST | MIRROR Panel Assessed Time to Response (Time From the Date of Enrollment to the First Documented Response (PR, CR, CCR) | 49 days |
| Unlabeled TST | MIRROR Panel Assessed Time to Response (Time From the Date of Enrollment to the First Documented Response (PR, CR, CCR) | 69 days |
p-value: 0.119Log Rank
Secondary
MIRROR Panel Assessments of Duration of Complete Response (Time From the First Documented Response to the First Documented Progression)
Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).
Time frame: The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001
Population: Intent-to-Treat (ITT) Exposed Population: all participants who were enrolled into the study and received at least one dose of study drug. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST | MIRROR Panel Assessments of Duration of Complete Response (Time From the First Documented Response to the First Documented Progression) | NA months |
| Unlabeled TST | MIRROR Panel Assessments of Duration of Complete Response (Time From the First Documented Response to the First Documented Progression) | NA months |
p-value: 0.495Log Rank
Secondary
MIRROR Panel Assessments of Duration of Confirmed Response (Time From the First Documented Response to the First Documented Progression)
Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).
Time frame: The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001
Population: ITT-Exposed Population. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST | MIRROR Panel Assessments of Duration of Confirmed Response (Time From the First Documented Response to the First Documented Progression) | NA months |
| Unlabeled TST | MIRROR Panel Assessments of Duration of Confirmed Response (Time From the First Documented Response to the First Documented Progression) | 18 months |
p-value: 0.677Log Rank
Secondary
Nadir Values for ANC, a Hematologic Parameter
Nadir is defined as the lowest laboratory value recorded following the administration of study medication. ANC is a measure of the number of neutrophil granulocytes present in the blood. Neutrophils are a type of white blood cell that fights against infection.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants with hematological toxicity were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST | Nadir Values for ANC, a Hematologic Parameter | 1.3 Cells/millimeters cubed (mm^3) |
| Unlabeled TST | Nadir Values for ANC, a Hematologic Parameter | 2.6 Cells/millimeters cubed (mm^3) |
| Unlabeled TST Crossover | Nadir Values for ANC, a Hematologic Parameter | 0.8 Cells/millimeters cubed (mm^3) |
Secondary
Nadir Values for Hemoglobin, a Hematologic Parameter
Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST | Nadir Values for Hemoglobin, a Hematologic Parameter | 11 Grams/dL |
| Unlabeled TST | Nadir Values for Hemoglobin, a Hematologic Parameter | 12.5 Grams/dL |
| Unlabeled TST Crossover | Nadir Values for Hemoglobin, a Hematologic Parameter | 10.2 Grams/dL |
Secondary
Nadir Values for the Hematologic Parameters Platelets and WBC Count
Nadir is defined as the lowest laboratory value recorded following the administration of study medication. Platelets and WBCs are types of blood cells.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TST and Iodine I 131 TST | Nadir Values for the Hematologic Parameters Platelets and WBC Count | WBC count (1000 cells/microliter) | 2.3 cells/microliter |
| TST and Iodine I 131 TST | Nadir Values for the Hematologic Parameters Platelets and WBC Count | Platelets (10000 cells/microliter) | 69 cells/microliter |
| Unlabeled TST | Nadir Values for the Hematologic Parameters Platelets and WBC Count | Platelets (10000 cells/microliter) | 162.5 cells/microliter |
| Unlabeled TST | Nadir Values for the Hematologic Parameters Platelets and WBC Count | WBC count (1000 cells/microliter) | 4.4 cells/microliter |
| Unlabeled TST Crossover | Nadir Values for the Hematologic Parameters Platelets and WBC Count | Platelets (10000 cells/microliter) | 50 cells/microliter |
| Unlabeled TST Crossover | Nadir Values for the Hematologic Parameters Platelets and WBC Count | WBC count (1000 cells/microliter) | 1.7 cells/microliter |
Secondary
Number of Participants (Par.) With a Confirmed Response (CR, CCR, or PR) as Assessed by the MIRROR Panel
Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present), or Partial Response (PR: \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).
Time frame: The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001
Population: ITT-Exposed Population. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and Iodine I 131 TST | Number of Participants (Par.) With a Confirmed Response (CR, CCR, or PR) as Assessed by the MIRROR Panel | 23 participants |
| Unlabeled TST | Number of Participants (Par.) With a Confirmed Response (CR, CCR, or PR) as Assessed by the MIRROR Panel | 6 participants |
p-value: 0.001Fisher Exact
Secondary
Number of Participants With an Infection for Which Anti-infectives Were Administered
Anti-infectives are capable of acting against infection, by inhibiting the spread of an infectious agent or by killing the infectious agent outright. Anti-infective is a general term that encompasses antibacterials, antibiotics, antifungals, antiprotozoans, and antivirals.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. Only those participants who had an infection during the study and during the follow-up period were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With an Infection for Which Anti-infectives Were Administered | Anti-infective Administered | 16 participants |
| TST and Iodine I 131 TST | Number of Participants With an Infection for Which Anti-infectives Were Administered | Anti-infective Not Administered | 2 participants |
| Unlabeled TST | Number of Participants With an Infection for Which Anti-infectives Were Administered | Anti-infective Administered | 9 participants |
| Unlabeled TST | Number of Participants With an Infection for Which Anti-infectives Were Administered | Anti-infective Not Administered | 0 participants |
| Unlabeled TST Crossover | Number of Participants With an Infection for Which Anti-infectives Were Administered | Anti-infective Administered | 6 participants |
| Unlabeled TST Crossover | Number of Participants With an Infection for Which Anti-infectives Were Administered | Anti-infective Not Administered | 1 participants |
Secondary
Number of Participants With a Time to Death From the Last Dose of Study Drug Less Than or Equal to 30 Days or More Than 30 Days
Time to death from the last dose of study drug is the time from the last dose of study drug administered to the date of death. Deaths due to progressive disease or to another reason (Other) were not captured as serious adverse events (SAEs) and are thus not included in the SAE module.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants who died by the completion of LTFU were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With a Time to Death From the Last Dose of Study Drug Less Than or Equal to 30 Days or More Than 30 Days | =<30 Days | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With a Time to Death From the Last Dose of Study Drug Less Than or Equal to 30 Days or More Than 30 Days | >30 Days | 25 participants |
| Unlabeled TST | Number of Participants With a Time to Death From the Last Dose of Study Drug Less Than or Equal to 30 Days or More Than 30 Days | =<30 Days | 0 participants |
| Unlabeled TST | Number of Participants With a Time to Death From the Last Dose of Study Drug Less Than or Equal to 30 Days or More Than 30 Days | >30 Days | 10 participants |
| Unlabeled TST Crossover | Number of Participants With a Time to Death From the Last Dose of Study Drug Less Than or Equal to 30 Days or More Than 30 Days | =<30 Days | 0 participants |
| Unlabeled TST Crossover | Number of Participants With a Time to Death From the Last Dose of Study Drug Less Than or Equal to 30 Days or More Than 30 Days | >30 Days | 13 participants |
Secondary
Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Causality of AEs was determined by the investigators as none, remote, possible, probable, or highly probable. AEs considered by the investigator as being at least remotely related to the study treatment were considered to be DR AEs. White blood cell (WBC) count and absolute neutrophil count (ANC) were measured as cells per millimeters cubed (mm\^3); hemoglobin was measured in grams per deciliter (g/dL).
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants with any drug-related adverse events were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | WBC <2000 cells/mm^3 | 18 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Cough | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Dyspnoea | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Bronchitis | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Dizziness | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Fatigue | 12 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pyrexia | 12 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Chills | 10 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pain | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Malaise | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Asthenia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Chest discomfort | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Feeling hot | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Oedema peripheral | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Influenza like illness | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Nausea | 20 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Diarrhoea | 4 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Abdominal discomfort | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Dyspepsia | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Vomiting | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Abdominal pain upper | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Constipation | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | ANC <1000 cells/mm^3 | 14 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Platelates <50000 cells/mm^3 | 15 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Hemoglobin < 8.0 g/dL | 6 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Rash | 5 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Erythema | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pruritus | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Hyperhidrosis | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Urticaria | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Night sweats | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Throat irritation | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Oropharyngeal pain | 4 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Nasal congestion | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Sinus congestion | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Arthralgia | 8 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Myalgia | 8 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Back pain | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Neck pain | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Upper respiratory tract infection | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pneumonia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Sinusitis | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Headache | 5 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Paraesthesia | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Thrombocytopenia | 6 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Anaemia | 5 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Lymphadenopathy | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Lymph node pain | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Neutropenia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pancytopenia | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Myelodysplastic syndrome | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Basal cell carcinoma | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Body temperature increased | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Weight decreased | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Insomnia | 4 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Decreased appetite | 6 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Flushing | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Hypothyroidism | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Ear pruritus | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Platelates <50000 cells/mm^3 | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Erythema | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pruritus | 3 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Constipation | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Urticaria | 3 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Night sweats | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Cough | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Lymphadenopathy | 3 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Upper respiratory tract infection | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Throat irritation | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Hemoglobin < 8.0 g/dL | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Body temperature increased | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Dizziness | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pancytopenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Lymph node pain | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Basal cell carcinoma | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Oropharyngeal pain | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pneumonia | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Fatigue | 11 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Hypothyroidism | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | WBC <2000 cells/mm^3 | 4 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pyrexia | 6 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Nasal congestion | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Bronchitis | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Chills | 7 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Rash | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Dyspnoea | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pain | 3 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Abdominal pain upper | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Vomiting | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Malaise | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Sinus congestion | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Sinusitis | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Asthenia | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | ANC <1000 cells/mm^3 | 4 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Ear pruritus | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Chest discomfort | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Myelodysplastic syndrome | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Headache | 5 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Feeling hot | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Arthralgia | 5 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Anaemia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Oedema peripheral | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Insomnia | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Myalgia | 5 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Influenza like illness | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Decreased appetite | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Weight decreased | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Nausea | 5 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Flushing | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Paraesthesia | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Diarrhoea | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Back pain | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Hyperhidrosis | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Abdominal discomfort | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Neutropenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Neck pain | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Dyspepsia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Thrombocytopenia | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Dyspepsia | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Vomiting | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Abdominal pain upper | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Constipation | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | WBC <2000 cells/mm^3 | 11 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Anaemia | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | ANC <1000 cells/mm^3 | 11 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Platelates <50000 cells/mm^3 | 9 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Hemoglobin < 8.0 g/dL | 3 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Lymphadenopathy | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Rash | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Hypothyroidism | 3 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Erythema | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Lymph node pain | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pruritus | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Urticaria | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Neutropenia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Decreased appetite | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Throat irritation | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Oropharyngeal pain | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pancytopenia | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Nasal congestion | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Dyspnoea | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Ear pruritus | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Sinus congestion | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Arthralgia | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Myelodysplastic syndrome | 4 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Myalgia | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Back pain | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Basal cell carcinoma | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Neck pain | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Hyperhidrosis | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Night sweats | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Flushing | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Cough | 4 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Upper respiratory tract infection | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Sinusitis | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Thrombocytopenia | 3 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Insomnia | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Fatigue | 6 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pneumonia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pyrexia | 3 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Chills | 3 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Bronchitis | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Pain | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Body temperature increased | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Malaise | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Asthenia | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Chest discomfort | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Feeling hot | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Headache | 4 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Oedema peripheral | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Dizziness | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Influenza like illness | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Nausea | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Diarrhoea | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Paraesthesia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Abdominal discomfort | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants | Weight decreased | 1 participants |
Secondary
Number of Participants With the Indicated Fatal SAEs Related to Study Drug
An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life-threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the investigator's medical judgement.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants who experienced any fatal SAE were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Myelodysplastic syndrome | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Acute myeloid leukemia | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Chronic myelomonocytic leukaemia | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Thrombocytopenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Thrombocytopenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Myelodysplastic syndrome | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Chronic myelomonocytic leukaemia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Acute myeloid leukemia | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Thrombocytopenia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Acute myeloid leukemia | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Chronic myelomonocytic leukaemia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Myelodysplastic syndrome | 3 participants |
Secondary
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants
AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants with any Grade 3 or Grade 4 AEs experienced by 3 or more participants were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | ANC <1000 cells/mm^3 | 14 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Anaemia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Myelodysplastic syndrome | 4 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | WBC <2000 cells/mm^3 | 18 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Neutropenia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Basal cell carcinoma | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Thrombocytopenia | 5 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Pneumonia | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Platelets <50000 cells/mm^3 | 15 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Dyspnoea | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Pancytopenia | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Hemoglobin <8.0 g/dL | 6 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Basal cell carcinoma | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Pancytopenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | WBC <2000 cells/mm^3 | 4 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | ANC <1000 cells/mm^3 | 4 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Platelets <50000 cells/mm^3 | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Hemoglobin <8.0 g/dL | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Myelodysplastic syndrome | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Thrombocytopenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Anaemia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Neutropenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Pneumonia | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Dyspnoea | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Pneumonia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Anaemia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | WBC <2000 cells/mm^3 | 11 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Neutropenia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Platelets <50000 cells/mm^3 | 9 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Pancytopenia | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | ANC <1000 cells/mm^3 | 11 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Basal cell carcinoma | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Dyspnoea | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Myelodysplastic syndrome | 4 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Thrombocytopenia | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants | Hemoglobin <8.0 g/dL | 3 participants |
Secondary
Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants
AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants with any Grade 3 or Grade 4 drug-related AEs experienced by 3 or more participants were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Anaemia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Myelodysplastic Syndrome | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Pancytopenia | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Thrombocytopenia | 5 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Basal Cell Carcinoma | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | WBC <2000 cells/mm^3 | 18 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Platelets <50000 cells/mm^3 | 15 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | ANC <1000 cells/mm^3 | 14 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Neutropenia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Hemoglobin <8.0 g/dL | 6 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Pneumonia | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Basal Cell Carcinoma | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | WBC <2000 cells/mm^3 | 4 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | ANC <1000 cells/mm^3 | 4 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Platelets <50000 cells/mm^3 | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Hemoglobin <8.0 g/dL | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Myelodysplastic Syndrome | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Thrombocytopenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Anaemia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Neutropenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Pancytopenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Pneumonia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Pancytopenia | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Anaemia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Platelets <50000 cells/mm^3 | 9 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | WBC <2000 cells/mm^3 | 11 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Neutropenia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | ANC <1000 cells/mm^3 | 11 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Basal Cell Carcinoma | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Myelodysplastic Syndrome | 4 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Pneumonia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Thrombocytopenia | 2 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants | Hemoglobin <8.0 g/dL | 3 participants |
Secondary
Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities
Adverse events were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | ANC | 14 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Hemoglobin | 6 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Platelets | 15 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | WBC count | 18 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | WBC count | 4 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | ANC | 4 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Platelets | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Hemoglobin | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | WBC count | 11 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Hemoglobin | 3 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Platelets | 9 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | ANC | 11 participants |
Secondary
Number of Participants With the Indicated Primary Cause of Death
Participants were categorized according to their primary cause of death. Deaths due to progressive disease or to another reason (Other) were not captured as serious adverse events (SAEs) and are thus not included in the SAE module.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants who died by the completion of LTFU were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With the Indicated Primary Cause of Death | Progression of lymphoma | 17 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Primary Cause of Death | Unknown | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Primary Cause of Death | Other | 7 participants |
| Unlabeled TST | Number of Participants With the Indicated Primary Cause of Death | Progression of lymphoma | 6 participants |
| Unlabeled TST | Number of Participants With the Indicated Primary Cause of Death | Unknown | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Primary Cause of Death | Other | 3 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Primary Cause of Death | Unknown | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Primary Cause of Death | Other | 3 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Primary Cause of Death | Progression of lymphoma | 9 participants |
Secondary
Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug
An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life-threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the investigator's medical judgement.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants who experienced any SAE were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Burkitt's lymphoma | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Thrombocytopenia | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Proteus infection | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Back pain | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Ulcer | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Mental status changes | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Abdominal pain upper | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Myelodysplastic Syndrome | 3 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Spinal cord compression | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Squamous cell carcinoma | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Basal cell carcinoma | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Gastrointestinal haemorrhage | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Pneumonia | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Bacteraemia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Hypothermia | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Pancytopenia | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Syncope | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Febrile neutropenia | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Bronchitis | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Pyrexia | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Acute myeloid leukaemia | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Chronic myelomonocytic leukaemia | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Retroperitoneal haemorrhage | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Cystitis | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Haemoptysis | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Renal cancer | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Constipation | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Squamous cell carcinoma of skin | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Myocardial infarction | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Cholecystitis acute | 1 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Subdural haematoma | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Small intestinal obstruction | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Cystitis | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Pneumonia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Syncope | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Retroperitoneal haemorrhage | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Small intestinal obstruction | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Spinal cord compression | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Bronchitis | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Chronic myelomonocytic leukaemia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Haemoptysis | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Squamous cell carcinoma of skin | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Subdural haematoma | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Thrombocytopenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Ulcer | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Myelodysplastic Syndrome | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Basal cell carcinoma | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Bacteraemia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Acute myeloid leukaemia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Pancytopenia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Squamous cell carcinoma | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Abdominal pain upper | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Back pain | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Burkitt's lymphoma | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Cholecystitis acute | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Constipation | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Febrile neutropenia | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Gastrointestinal haemorrhage | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Hypothermia | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Mental status changes | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Myocardial infarction | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Proteus infection | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Pyrexia | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Renal cancer | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Burkitt's lymphoma | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Squamous cell carcinoma of skin | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Myocardial infarction | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Cholecystitis acute | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Haemoptysis | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Constipation | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Chronic myelomonocytic leukaemia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Bronchitis | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Cystitis | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Syncope | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Pancytopenia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Febrile neutropenia | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Proteus infection | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Gastrointestinal haemorrhage | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Spinal cord compression | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Renal cancer | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Hypothermia | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Acute myeloid leukaemia | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Bacteraemia | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Small intestinal obstruction | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Basal cell carcinoma | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Pneumonia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Myelodysplastic Syndrome | 4 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Pyrexia | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Ulcer | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Mental status changes | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Abdominal pain upper | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Thrombocytopenia | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Retroperitoneal haemorrhage | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Back pain | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Subdural haematoma | 1 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug | Squamous cell carcinoma | 1 participants |
Secondary
Number of Participants With the Indicated Type of Infection
An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Specimen samples of the body fluid are cultured for testing whether the infectious organism is present and grown in the culture media to assess the growth pattern of the organisms present in the specimen. The culture results could be positive or negative. The positive culture results indicate that the tested participant has the infection under investigation, in which case therapeutic treatment with anti-infective is required.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST | Number of Participants With the Indicated Type of Infection | Sepsis; n=18, 9, 7 | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Type of Infection | Any Infection; n=42, 36, 19 | 18 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Type of Infection | No Infection; n=42, 36, 19 | 24 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Type of Infection | Pneumonia; n=18, 9, 7 | 2 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Type of Infection | Endocarditis/pericarditis; n=18, 9, 7 | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Type of Infection | Peritonitis; n=18, 9, 7 | 0 participants |
| TST and Iodine I 131 TST | Number of Participants With the Indicated Type of Infection | Other infections; n=18, 9, 7 | 17 participants |
| Unlabeled TST | Number of Participants With the Indicated Type of Infection | Peritonitis; n=18, 9, 7 | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Type of Infection | Pneumonia; n=18, 9, 7 | 2 participants |
| Unlabeled TST | Number of Participants With the Indicated Type of Infection | Other infections; n=18, 9, 7 | 8 participants |
| Unlabeled TST | Number of Participants With the Indicated Type of Infection | Sepsis; n=18, 9, 7 | 0 participants |
| Unlabeled TST | Number of Participants With the Indicated Type of Infection | Endocarditis/pericarditis; n=18, 9, 7 | 1 participants |
| Unlabeled TST | Number of Participants With the Indicated Type of Infection | Any Infection; n=42, 36, 19 | 9 participants |
| Unlabeled TST | Number of Participants With the Indicated Type of Infection | No Infection; n=42, 36, 19 | 27 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Type of Infection | Any Infection; n=42, 36, 19 | 7 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Type of Infection | No Infection; n=42, 36, 19 | 12 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Type of Infection | Sepsis; n=18, 9, 7 | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Type of Infection | Peritonitis; n=18, 9, 7 | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Type of Infection | Pneumonia; n=18, 9, 7 | 0 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Type of Infection | Other infections; n=18, 9, 7 | 7 participants |
| Unlabeled TST Crossover | Number of Participants With the Indicated Type of Infection | Endocarditis/pericarditis; n=18, 9, 7 | 0 participants |
Secondary
Overall Survival
Overall survival is defined as the time from the treatment start date to the date of death by any cause.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. Only those participants who died during the study and during the follow-up period were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST | Overall Survival | 71.5 months |
| Unlabeled TST | Overall Survival | 70.0 months |
| Unlabeled TST Crossover | Overall Survival | 51.4 months |
Secondary
Time to Human Anti-Murine Antibodies (HAMA) Positivity From the First Dosimetric Dose
Tositumomab is a murine (mouse) antibody (immunoglobulin) of the IgG2a subclass. Participants in this study were evaluated to determine whether they developed an immune response to study treatment as evident by human anti-mouse antibodies (HAMA) after administration of tositumomab and iodine I 131 tositumomab. A positive HAMA value indicates that the participant developed human anti-mouse antibodies above the HAMA assay threshold, and a negative HAMA value indicates either the absence or below threshold level of human anti-mouse antibodies.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. Participants who converted from being negative for HAMA at Baseline to being positive for HAMA following treatment were evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TST and Iodine I 131 TST | Time to Human Anti-Murine Antibodies (HAMA) Positivity From the First Dosimetric Dose | 163 days | Standard Deviation 108.4 |
| Unlabeled TST | Time to Human Anti-Murine Antibodies (HAMA) Positivity From the First Dosimetric Dose | 62.6 days | Standard Deviation 49 |
Secondary
Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations
Nadir is defined as the lowest laboratory value recorded following the administration of the study medication. Time to recovery to baseline in hematologic laboratory evaluations is the time required for recovery from nadir values to baseline values. Hematologic laboratory evaluations included ANC, hemoglobin (Hb), platelets (Plt), and WBC count.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants with hematological toxicity were evaluated. The numbers analyzed in the category titles reflect the number of participants with the event of interest plus the number of participants who were censored. A censored value indicates that the participant did not have the event of interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TST and Iodine I 131 TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir ANC, n=42, 35, 19 | 48 days |
| TST and Iodine I 131 TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir Hb, n=42, 36, 19 | 49 days |
| TST and Iodine I 131 TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir Plt, n=42, 36, 19 | 36.5 days |
| TST and Iodine I 131 TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir WBC count, n=42, 36, 19 | 46.5 days |
| TST and Iodine I 131 TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline ANC, n=42, 35, 19 | 63 days |
| TST and Iodine I 131 TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline Hb, n=42, 36, 19 | 69 days |
| TST and Iodine I 131 TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline Plt, n=42, 36, 19 | 55 days |
| TST and Iodine I 131 TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline WBC, n=42, 36, 19 | 76 days |
| Unlabeled TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir Plt, n=42, 36, 19 | 43.5 days |
| Unlabeled TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline Plt, n=42, 36, 19 | 44 days |
| Unlabeled TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir WBC count, n=42, 36, 19 | 42.5 days |
| Unlabeled TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline ANC, n=42, 35, 19 | 41 days |
| Unlabeled TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline Hb, n=42, 36, 19 | 49 days |
| Unlabeled TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir ANC, n=42, 35, 19 | 39 days |
| Unlabeled TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir Hb, n=42, 36, 19 | 43.5 days |
| Unlabeled TST | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline WBC, n=42, 36, 19 | 54 days |
| Unlabeled TST Crossover | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir Plt, n=42, 36, 19 | 36 days |
| Unlabeled TST Crossover | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir Hb, n=42, 36, 19 | 48 days |
| Unlabeled TST Crossover | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir ANC, n=42, 35, 19 | 44 days |
| Unlabeled TST Crossover | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to nadir WBC count, n=42, 36, 19 | 43 days |
| Unlabeled TST Crossover | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline Plt, n=42, 36, 19 | 62.5 days |
| Unlabeled TST Crossover | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline Hb, n=42, 36, 19 | 97 days |
| Unlabeled TST Crossover | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline ANC, n=42, 35, 19 | 84 days |
| Unlabeled TST Crossover | Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations | Time to recovery to baseline WBC, n=42, 36, 19 | 91 days |
Secondary
Time to Progression of Disease or Death as Assessed by the Investigator
Progression-free survival or time to progression is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. Participants who experienced progression or died (n=36, 33) and participants who were censored (n=6, 3) were analyzed. A censored value indicates that the participant did not have the event of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST | Time to Progression of Disease or Death as Assessed by the Investigator | 6.0 months |
| Unlabeled TST | Time to Progression of Disease or Death as Assessed by the Investigator | 3.8 months |
Secondary
Time to Progression of Disease or Death in Participants Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator
Progression-free survival or time to progression is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death.
Time frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
Population: ITT-Exposed Population. All participants receiving Unlabeled TST who received the crossover treatment and those who progressed/died were analyzed. Participants who experienced progression or died (n=18, 17) and participants who were censored (n=1, 2) were analyzed. A censored value indicates that the participant did not have the event of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST | Time to Progression of Disease or Death in Participants Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 3.1 months |
| Unlabeled TST | Time to Progression of Disease or Death in Participants Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator | 15.0 months |