Lymphoma, Non-Hodgkin
Conditions
Keywords
non-Hodgkin's Lymphoma, radioimmunotherapy, NHL, Bexxar, lymphoma, Tositumomab
Brief summary
The results from Phase 1/2 (RIT-I-000) and Phase 2 (RIT-II-001) studies of Tositumomab and Iodine I 131 Tositumomab (TST/I-131 TST) demonstrated that TST/ I-131 TST produced a high response rate in patients with chemotherapy-relapsed/refractory, low-grade or transformed low-grade Non-Hodgkin's Lymphoma (NHL). On the basis of these results this study was designed to compare the efficacy of TST/ I-131 TST to the last qualifying chemotherapy regimen in patients with chemotherapy-refractory, low-grade or transformed low-grade NHL.
Interventions
BIOLOGICALTositumomab and Iodine I 131 Tositumomab
Dosimetric Dose: 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by I-131 TST (35 mg of TST, of which 1-2 mg had been labeled with 5 mCi of Iodine-131) infused over 30 minutes (inclusive of a 10-minute flush). Therapeutic Dose: 7 to 14 days after the dosimetric dose, 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by I-131 TST (35 mg of TST labeled with enough Iodine-131 to administer the specified whole body radiation dose determined for the subject) infused over 30 minutes (inclusive of a 10-minute flush). The desired total body dose was 65 cGy for subjects with a baseline platelet count of 100,001-149,999/mm3 and 75 cGy for patients with a baseline platelet count ≥150,000/mm3. Obese patients received an attenuated dose by not including subject mass over 137% of their calculated lean body mass in their calculated lean body mass in the dose calculation.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female subjects ≥18 years of age with histologically confirmed at initial diagnosis, previously treated (at least 2 prior chemotherapy regimens), low-grade NHL or low-grade lymphoma that had transformed to intermediate- or high-grade histology.
Exclusion criteria
* Subjects with 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 intratrebecular space involved exceeds 10% in a unilateral biopsy. The mean of bilateral biopsies must be no more than 25%. * Cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks prior to study entry or persistent clinical evidence of toxicity. * Prior stem cell transplant. * Active obstructive hydronephrosis. * Evidence of active infection requiring intravenous (IV) 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 the subject has been disease-free for 5 years. * Known HIV infection. * Known brain or leptomeningeal metastases. * Subjects who are pregnant or nursing. * Previous allergic reactions to iodine. This does not include reactions to intravenous iodine-containing contrast materials. * Prior exposure to monoclonal or polyclonal antibodies of any non-human species for either diagnostic or therapeutic purposes, including engineered chimeric and humanized antibodies. * Prior radioimmunotherapy. * Progressive disease within 1 year of irradiation arising in a field that has been previously irradiated with \>3500 cGy. * Current use of either approved or non-approved (through another protocol) anti-cancer drugs or biologics * De novo intermediate- or high-grade lymphoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (Par.) Receiving TST and I 131 TST With a Response >=30 Days Versus Par. With a Response >=30 Days After Their Last Qualifying Chemotherapy Regimen (LQCR), Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | Par. with response are those with complete response (CR; complete resolution of all disease-related radiological abnormalities and the disappearance of all signs/symptoms related to disease), complete response unconfirmed (CRu; meets characteristics of CR, except the nodal size hasn't regressed sufficiently, or there is indeterminate bone marrow), or partial response (PR; \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions). Participants' LQCR was used as a comparator for subsequent treatment with Iodine I 131TST. |
| Duration of Response for Par. Receiving TST and I 131 TST With a Response >=30 Days Versus the Number of Par. With a Response >=30 Days After Their LQCR, as Assessed by the MIRROR Panel | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | Duration of response is defined as the time from the first documented response (for par. with complete response, complete response unconfirmed, or partial response) until disease progression (DP). DP is defined as a \>=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) of the sum of the products of the longest perpendicular diameters of all measurable 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression of Disease or Death, as Assessed by the Investigator | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | Time to progression or progression-free survival is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death. Disease progression is defined as a \>=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter by radiographic evaluation or \>1 cm in diameter by physical examination. |
| Time to Treatment Failure, as Assessed by the Investigator | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | Time to treatment failure is defined as the length of time from the date of enrollment to the first incidence of treatment withdrawal, study removal, progression, and/or alternative therapy for the participant's lymphoma, or death. |
| Overall Survival | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | Overall survival is defined as the time from the treatment start date to the date of death from any cause. |
| Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | Participants with response include those with CR, CCR, or PR. Criteria for CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Criteria for CCR: complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Criteria for PR: \>=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 the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | 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. The Investigator assessed whether the adverse event was related to study drug. |
| Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. |
| Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. The Investigator assessed whether the AE was possibly or probably related to study drug. In addition, all laboratory-derived hematologic toxicities (values outside the normal range) were assumed to be possibly or probably related to study drug. |
| Number of Participants With the Indicated Primary Cause of Death | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | The primary cause of death of the participants was assessed by the Investigator. |
| Number of Participants With the Indicated Time to Death From the Last Dose of Study Drug | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | Time to death from the last dose of study drug is the time period difference between when study drug treatment stopped and when death occurred. |
| Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | Participants with response include those with CR, CCR, or PR. Criteria for CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Criteria for CCR: complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Criteria for PR: \>=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 the Indicated Fatal SAEs Related to Study Drug | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | 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 AEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement. |
| Number of Participants With the Indicated SAEs Related to Study Drug | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | 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 Type of Infection | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | 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 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | 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 Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Before Receiving the Dosimetric Dose) But Positive or Negative After Receiving the Dosimetric Dose | HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | The administration of murine antibodies may form HAMA. A HAMA assay was performed using the ImmunoSTRIP HAMA IgG enzyme-linked immune absorbent assay by a central laboratory (Covance Classic Laboratory Services, Indianapolis, IN). Fludarabine, a known immunosuppressant, might decrease HAMA production in addition to reducing bone marrow involvement. To be positive, a participant had to have a positive HAMA assessment at any follow-up visit. |
| Time to HAMA Positivity From the First Dosimetric Dose | HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | HAMA are human immunoglobulins with specificity for mouse immunoglobulins. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment. Time to HAMA positivity was calculated as the difference between the day on which HAMA positivity occurred and the first dosimetric dose administration day. |
| Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | 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. Grade 3/4 hematological toxicities: hemoglobin \<8.0 g/dL; platelets \<50,000 cells per millimeters (mm)\^3; ANC \<1000 cells per mm\^3; WBC \<2000 cells per mm\^3. |
| Number of Participants With Hypothyroidism Prior to Therapy and After the Therapeutic Dose | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | Thyroid function was determined periodically, including during follow-up, in order to assess if there was any effect of the Iodine 131 on thyroid function. Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone. |
| Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | 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 judgment. |
| Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator | Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months | Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with CR, CCR , or PR. A confirmed response (CR/CCR/PR) had to be confirmed by a consecutive response (\>=28 days \[ 4 weeks\] later) that was the same or better. Individual confirmed response data only counts that response confirmed by the same response; thus, not all possible combinations are represented. |
Participant flow
Pre-assignment details
Participants (par.) received radioimmunotherapy of tositumomab (TST) and Iodine I 131 TST in 2 phases (Ph.): Ph. 1, dosimetric dose; Ph. 2, therapeutic dose. Par. were evaluated until disease progression, they died, or they were on study for 2 years. Par. completing 2 years of study could enter a long-term follow-up study (BEX104526; NCT00240591).
Participants by arm
| Arm | Count |
|---|---|
| TST and I 131 TST Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie \[mCi\] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray \[cGy\] or 65 cGy). The TD 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. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Dosimetric and Therapeutic Treatment | Condition/Illness; Study Drug Unrelated | 2 |
| Dosimetric and Therapeutic Treatment | Death | 1 |
| Dosimetric and Therapeutic Treatment | Did Not Receive Study Drug | 1 |
| Dosimetric and Therapeutic Treatment | Enrolled into Study BEX104526 | 7 |
| Dosimetric and Therapeutic Treatment | Non-compliant or Uncooperative | 1 |
| Dosimetric and Therapeutic Treatment | Progressive Disease | 49 |
| Long-Term Follow-Up | Death | 3 |
Baseline characteristics
| Characteristic | TST and I 131 TST |
|---|---|
| Age, Continuous | 59.4 Years STANDARD_DEVIATION 10.5 |
| Gender Female | 22 Participants |
| Gender Male | 38 Participants |
| Race/Ethnicity, Customized Black | 1 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants |
| Race/Ethnicity, Customized White | 58 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 59 / 60 |
| serious Total, serious adverse events | 30 / 60 |
Outcome results
Primary
Duration of Response for Par. Receiving TST and I 131 TST With a Response >=30 Days Versus the Number of Par. With a Response >=30 Days After Their LQCR, as Assessed by the MIRROR Panel
Duration of response is defined as the time from the first documented response (for par. with complete response, complete response unconfirmed, or partial response) until disease progression (DP). DP is defined as a \>=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) of the sum of the products of the longest perpendicular diameters of all measurable 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.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. Only those participants with complete response, complete response unconfirmed, or partial response were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and I 131 TST | Duration of Response for Par. Receiving TST and I 131 TST With a Response >=30 Days Versus the Number of Par. With a Response >=30 Days After Their LQCR, as Assessed by the MIRROR Panel | 6.5 months |
| LQCR | Duration of Response for Par. Receiving TST and I 131 TST With a Response >=30 Days Versus the Number of Par. With a Response >=30 Days After Their LQCR, as Assessed by the MIRROR Panel | 3.5 months |
Primary
Number of Participants (Par.) Receiving TST and I 131 TST With a Response >=30 Days Versus Par. With a Response >=30 Days After Their Last Qualifying Chemotherapy Regimen (LQCR), Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel
Par. with response are those with complete response (CR; complete resolution of all disease-related radiological abnormalities and the disappearance of all signs/symptoms related to disease), complete response unconfirmed (CRu; meets characteristics of CR, except the nodal size hasn't regressed sufficiently, or there is indeterminate bone marrow), or partial response (PR; \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions). Participants' LQCR was used as a comparator for subsequent treatment with Iodine I 131TST.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TST and I 131 TST | Number of Participants (Par.) Receiving TST and I 131 TST With a Response >=30 Days Versus Par. With a Response >=30 Days After Their Last Qualifying Chemotherapy Regimen (LQCR), Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel | 26 participants |
| LQCR | Number of Participants (Par.) Receiving TST and I 131 TST With a Response >=30 Days Versus Par. With a Response >=30 Days After Their Last Qualifying Chemotherapy Regimen (LQCR), Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel | 5 participants |
p-value: <0.001McNemar
Secondary
Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Before Receiving the Dosimetric Dose) But Positive or Negative After Receiving the Dosimetric Dose
The administration of murine antibodies may form HAMA. A HAMA assay was performed using the ImmunoSTRIP HAMA IgG enzyme-linked immune absorbent assay by a central laboratory (Covance Classic Laboratory Services, Indianapolis, IN). Fludarabine, a known immunosuppressant, might decrease HAMA production in addition to reducing bone marrow involvement. To be positive, a participant had to have a positive HAMA assessment at any follow-up visit.
Time frame: HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. Only those participants evaluable for HAMA were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Before Receiving the Dosimetric Dose) But Positive or Negative After Receiving the Dosimetric Dose | Positive | 5 participants |
| TST and I 131 TST | Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Before Receiving the Dosimetric Dose) But Positive or Negative After Receiving the Dosimetric Dose | Negative | 53 participants |
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 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
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 I 131 TST | Number of Participants With an Infection for Which Anti-infectives Were Administered | Anti-infective Administered | 12 participants |
| TST and I 131 TST | Number of Participants With an Infection for Which Anti-infectives Were Administered | Anti-infective Not Administered | 3 participants |
Secondary
Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator
Responses had to be confirmed by 2 separate evaluations occurring \>=4 weeks apart. Par. with confirmed response include those with CR, CCR , or PR. A confirmed response (CR/CCR/PR) had to be confirmed by a consecutive response (\>=28 days \[ 4 weeks\] later) that was the same or better. Individual confirmed response data only counts that response confirmed by the same response; thus, not all possible combinations are represented.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator | Confirmed Response (CR, CCR, or PR) | 30 participants |
| TST and I 131 TST | Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator | CR | 9 participants |
| TST and I 131 TST | Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator | CCR | 1 participants |
| TST and I 131 TST | Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator | CR+CCR | 11 participants |
| TST and I 131 TST | Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator | PR | 18 participants |
Secondary
Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator
Participants with response include those with CR, CCR, or PR. Criteria for CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Criteria for CCR: complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Criteria for PR: \>=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 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. Only those participants evaluable for response were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator | Response (CR, CCR, or PR) | 39 participants |
| TST and I 131 TST | Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator | CR | 11 participants |
| TST and I 131 TST | Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator | CCR | 1 participants |
| TST and I 131 TST | Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator | CR+CCR | 12 participants |
| TST and I 131 TST | Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator | PR | 27 participants |
Secondary
Number of Participants With Hypothyroidism Prior to Therapy and After the Therapeutic Dose
Thyroid function was determined periodically, including during follow-up, in order to assess if there was any effect of the Iodine 131 on thyroid function. Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. Participants who were evaluable for thyroid function assessment were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With Hypothyroidism Prior to Therapy and After the Therapeutic Dose | Prior to therapy | 8 participants |
| TST and I 131 TST | Number of Participants With Hypothyroidism Prior to Therapy and After the Therapeutic Dose | After therapeutic dose | 7 participants |
Secondary
Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator
Participants with response include those with CR, CCR, or PR. Criteria for CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. Criteria for CCR: complete resolution of all disease-related symptoms, but residual foci, thought to be residual scar tissue, are present. Criteria for PR: \>=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 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. Only those participants evaluable for response were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator | CR | 11 participants |
| TST and I 131 TST | Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator | CR+CCR | 12 participants |
| TST and I 131 TST | Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator | CCR | 1 participants |
| TST and I 131 TST | Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator | PR | 27 participants |
| TST and I 131 TST | Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator | Response (CR, CCR, or PR) | 39 participants |
| LQCR | Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator | PR | 15 participants |
| LQCR | Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator | Response (CR, CCR, or PR) | 17 participants |
| LQCR | Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator | CR | 1 participants |
| LQCR | Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator | CCR | 1 participants |
| LQCR | Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator | CR+CCR | 2 participants |
Secondary
Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of 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. The Investigator assessed whether the adverse event was related to study drug.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. All participants who experienced any AE related to study drug were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Absolute Neutrophil Count (ANC) <1000 cells/cm^3 | 35 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Platelets <50000 cells/cm^3 | 29 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | White Blood Cells (WBC) <2000 cells/cm^3 | 29 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Hemoglobin <8.0 grams/deciliter (g/dL) | 13 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Fatigue | 27 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Pyrexia | 19 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Chills | 11 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Nausea | 16 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Vomiting | 9 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Diarrhoea | 4 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Thrombocytopenia | 10 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Neutropenia | 9 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Anaemia | 7 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Leukopenia | 4 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Pruritus | 8 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Rash | 4 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Night sweats | 3 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Cough | 7 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Dyspnoea | 7 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Throat irritation | 4 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Productive cough | 3 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Headache | 5 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Dizziness | 3 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Somnolence | 3 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Decreased appetite | 11 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Arthralgia | 5 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Myalgia | 5 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Pain in extremity | 3 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Myelodysplastic syndrome | 4 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Hypothyroidism | 7 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Hypotension | 5 participants |
| TST and I 131 TST | Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants | Tachycardia | 3 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 AEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. All participants who experienced fatal SAEs were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Encephalopathy | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Lung adenocarcinoma | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Myelodysplastic syndrome | 2 participants |
| TST and I 131 TST | Number of Participants With the Indicated Fatal SAEs Related to Study Drug | Pulmonary hemorrhage | 1 participants |
Secondary
Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated 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 judgment.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. All participants who experienced fatal SAEs were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug | Pneumonia aspiration | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug | Non-Hodgkins lymphoma | 2 participants |
| TST and I 131 TST | Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug | Encephalopathy | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug | Dyspnea | 1 participants |
Secondary
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of 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 AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. All participants who experienced Grade 3 or Grade 4 AEs were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | ANC <1000 cells/cm^3 | 35 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | Platelets <50000 cells/cm^3 | 29 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | WBC <2000 cells/cm^3 | 29 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | Hemoglobin <8.0 g/dL | 13 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | Myelodysplastic syndrome | 4 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | Neutropenia | 9 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | Thrombocytopenia | 8 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | Anaemia | 4 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | Leukopenia | 3 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | Dyspnoea | 3 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants | Pleural effusion | 3 participants |
Secondary
Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of 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 AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE. The Investigator assessed whether the AE was possibly or probably related to study drug. In addition, all laboratory-derived hematologic toxicities (values outside the normal range) were assumed to be possibly or probably related to study drug.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. All participants who experienced Grade 3 or 4 AEs related to study drug were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants | ANC <1000 cells/cm^3 | 35 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants | Platelets <50000 cells/cm^3 | 29 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants | WBC <2000 cells/cm^3 | 29 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants | Hemoglobin <8.0 g/dL | 13 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants | Neutropenia | 9 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants | Thrombocytopenia | 8 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants | Anaemia | 4 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants | Leukopenia | 3 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants | Myelodysplastic syndrome | 4 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. Grade 3/4 hematological toxicities: hemoglobin \<8.0 g/dL; platelets \<50,000 cells per millimeters (mm)\^3; ANC \<1000 cells per mm\^3; WBC \<2000 cells per mm\^3.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | ANC | 35 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Hemoglobin | 13 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | Platelets | 29 participants |
| TST and I 131 TST | Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities | WBC count | 29 participants |
Secondary
Number of Participants With the Indicated Primary Cause of Death
The primary cause of death of the participants was assessed by the Investigator.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. All participants who died during the study were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With the Indicated Primary Cause of Death | Complications related to study drug | 0 participants |
| TST and I 131 TST | Number of Participants With the Indicated Primary Cause of Death | Other | 11 participants |
| TST and I 131 TST | Number of Participants With the Indicated Primary Cause of Death | Progression of lymphoma | 37 participants |
Secondary
Number of Participants With the Indicated 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 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. All participants who experienced SAEs were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Myelodysplastic syndrome | 4 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Squamous cell carcinoma | 2 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Basal cell carcinoma | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Colon cancer stage 0 | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Lung adenocarcinoma | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Refractory anaemia with an excess of blasts | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Squamous cell carcinoma of skin | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Anaemia | 2 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Leukopenia | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Neutropenia | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Chronic obstructive pulmonary disease | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Dyspnoea | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Pulmonary haemorrhage | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Pneumocystis jiroveci pneumonia | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Pneumonia | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Atrial flutter | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Subdural haematoma | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Arthralgia | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated SAEs Related to Study Drug | Encephalopathy | 1 participants |
Secondary
Number of Participants With the Indicated Time to Death From the Last Dose of Study Drug
Time to death from the last dose of study drug is the time period difference between when study drug treatment stopped and when death occurred.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. All participants who died during the study were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With the Indicated Time to Death From the Last Dose of Study Drug | <=30 Days | 1 participants |
| TST and I 131 TST | Number of Participants With the Indicated Time to Death From the Last Dose of Study Drug | >30 Days | 47 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 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. Only those participants who experienced any infection were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and I 131 TST | Number of Participants With the Indicated Type of Infection | No Infection; n=59 | 44 participants |
| TST and I 131 TST | Number of Participants With the Indicated Type of Infection | Sepsis; n=15 | 0 participants |
| TST and I 131 TST | Number of Participants With the Indicated Type of Infection | Pneumonia; n=15 | 5 participants |
| TST and I 131 TST | Number of Participants With the Indicated Type of Infection | Any Infection; n=59 | 15 participants |
| TST and I 131 TST | Number of Participants With the Indicated Type of Infection | Other Infections; n=15 | 14 participants |
Secondary
Overall Survival
Overall survival is defined as the time from the treatment start date to the date of death from any cause.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
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 I 131 TST | Overall Survival | 30.1 months |
Secondary
Time to HAMA Positivity From the First Dosimetric Dose
HAMA are human immunoglobulins with specificity for mouse immunoglobulins. HAMA assays were conducted in the laboratory to measure conversion to HAMA positivity following treatment. Time to HAMA positivity was calculated as the difference between the day on which HAMA positivity occurred and the first dosimetric dose administration day.
Time frame: HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. Participants who converted from being negative for HAMA at Baseline to being positive for HAMA following treatment were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and I 131 TST | Time to HAMA Positivity From the First Dosimetric Dose | 279 days |
Secondary
Time to Progression of Disease or Death, as Assessed by the Investigator
Time to progression or progression-free survival is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death. Disease progression is defined as a \>=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 cm in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. Only those participants who experienced disease progression or died were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and I 131 TST | Time to Progression of Disease or Death, as Assessed by the Investigator | 4.7 months |
Secondary
Time to Treatment Failure, as Assessed by the Investigator
Time to treatment failure is defined as the length of time from the date of enrollment to the first incidence of treatment withdrawal, study removal, progression, and/or alternative therapy for the participant's lymphoma, or death.
Time frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months
Population: ITT Exposed Population. Only those participants who experienced treatment failure were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and I 131 TST | Time to Treatment Failure, as Assessed by the Investigator | 4.6 months |