Lymphoma, Non-Hodgkin
Conditions
Keywords
Tositumomab and/or Iodine I 131 Tositumomab, B-cell non-Hodgkin's lymphoma, Dose-limiting toxicity, Bexxar
Brief summary
Phase I/II, single-center, dose-escalation study of the safety, pharmacokinetics, dosimetry, and efficacy of TST/I-131 TST for the treatment of patients with chemotherapy-refractory or resistant low-grade, intermediate-grade, or high-grade B-cell lymphoma. Subjects received 1 to 3 dosimetric doses followed by a therapeutic dose of TST/I-131 TST. Study BEX104526 was a follow-up study of the long-term safety and efficacy data from the surviving patients who completed at least 2 years of follow-up following administration of TST/I 131 TST on Study BEX104728. Dosimetric dose: Subjects received 1 to 3 dosimetric doses of TST/I-131 TST, followed by a therapeutic dose of TST/I-131 TST. Subjects received various doses of unlabeled TST (0, 95 or 475 mg) to determine the dose of unlabeled TST that optimized the radiation dose delivered to the tumor by TST/I-131 TST. The unlabeled TST was followed by 5 milliCurie (mCi) of I-131 TST. Serial whole body sodium iodide scintillation probe counts were obtained daily, for at least 5 days, in order to determine the rate of whole body clearance of radioactivity (residence time). The residence time was used to determine the radioactive clearance for the subject and the activity (in mCi) of I-131 required to deliver the desired TBD of radiation during the therapeutic dose. Because 475 mg was determined to be the optimal pre-dose of TST in the first subjects entered, the last 34 subjects received a single dosimetric dose that was preceded by an infusion of 475 mg of TST. Therapeutic dose: Groups of 3-6 subjects were enrolled at successively higher whole-body radiation dose levels beginning at a total body dose (TBD) of 25 centiGray (cGy). The TBD of each subsequent dose level was escalated by 10 cGy. Subjects who had undergone bone marrow transplantation (BMT) underwent a separate dose escalation (10 cGy TBD increase per dose level) beginning at a TBD level of 65 cGy. The MTD was defined as the highest dose level at which 0/3 or 1/6 subjects experienced dose-limiting toxicity (DLT). DLT was defined as follows: Any Grade 4 hematologic toxicity (National Cancer Institute \[NCI\] criteria) lasting greater than 7 days, or Any Grade 3 hematologic toxicity lasting greater than 2 weeks, or Any Grade 3 or 4 nonhematologic toxicity Redosing. Subjects who achieved tumor regression were considered for re-dosing, using the original therapeutic dose of TST/I-131 TST, at the time the tumor was no longer shrinking in an attempt to upgrade their response. Retreatment. Subjects who achieved partial (PR) or complete response (CR) were considered for retreatment following relapse of their NHL, if progression occurred ≥6 weeks following the therapeutic dose. The original therapeutic dose of TST/I-131 TST was given unless a grade 2 or greater toxicity had been encountered, in which case a reduced dose was administered for the repeat therapeutic dose.
Detailed description
Phase I/II, single-center, dose-escalation study of the safety, pharmacokinetics, dosimetry, and efficacy of TST/I-131 TST for the treatment of patients with chemotherapy-refractory or resistant low-grade, intermediate-grade, or high-grade B-cell lymphoma. Subjects received 1 to 3 dosimetric doses followed by a therapeutic dose of TST/I-131 TST. Study BEX104526 was a follow-up study of the long-term safety and efficacy data from the surviving patients who completed at least 2 years of follow-up following administration of TST/I 131 TST on Study BEX104728. Dosimetric dose: Subjects received 1 to 3 dosimetric doses of TST/I-131 TST, followed by a therapeutic dose of TST/I-131 TST. Subjects received various doses of unlabeled TST (0, 95 or 475 mg) to determine the dose of unlabeled TST that optimized the radiation dose delivered to the tumor by TST/I-131 TST. The unlabeled TST was followed by 5 milliCurie (mCi) of I-131 TST. Serial whole body sodium iodide scintillation probe counts were obtained daily, for at least 5 days, in order to determine the rate of whole body clearance of radioactivity (residence time). The residence time was used to determine the radioactive clearance for the subject and the activity (in mCi) of I-131 required to deliver the desired TBD of radiation during the therapeutic dose. Because 475 mg was determined to be the optimal pre-dose of TST in the first subjects entered, the last 34 subjects received a single dosimetric dose that was preceded by an infusion of 475 mg of TST. Therapeutic dose: Groups of 3-6 subjects were enrolled at successively higher whole-body radiation dose levels beginning at a total body dose (TBD) of 25 centiGray (cGy). The TBD of each subsequent dose level was escalated by 10 cGy. Subjects who had undergone bone marrow transplantation (BMT) underwent a separate dose escalation (10 cGy TBD increase per dose level) beginning at a TBD level of 65 cGy. The MTD was defined as the highest dose level at which 0/3 or 1/6 subjects experienced dose-limiting toxicity (DLT). DLT was defined as follows: Any Grade 4 hematologic toxicity (National Cancer Institute \[NCI\] criteria) lasting greater than 7 days, or Any Grade 3 hematologic toxicity lasting greater than 2 weeks, or Any Grade 3 or 4 nonhematologic toxicity Redosing: Subjects who achieved tumor regression were considered for re-dosing, using the original therapeutic dose of TST/I-131 TST, at the time the tumor was no longer shrinking in an attempt to upgrade their response. Retreatment: Subjects who achieved a partial response (PR) or complete response (CR) were considered for retreatment following relapse of their NHL, if progression occurred ≥6 weeks following the therapeutic dose. The original therapeutic dose of TST/I-131 TST was given unless a grade 2 or greater toxicity had been encountered, in which case a reduced dose was administered for the repeat therapeutic dose. Subjects who completed at least 2 years of follow-up in BEX104728 were enrolled in LTFU Study BEX104526 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 and disease status, including subsequent therapy for NHL, and for long-term safety, including the development of hypothyroidism, myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML), and any other secondary malignancies. Additionally, subjects were followed for the development of any adverse event(s) (AEs) deemed by the Principal Investigator as being possibly or probably related to a subject's treatment with TST/I-131 TST. Laboratory evaluations, consisting of thyroid stimulating hormone (TSH) level and complete blood cell count with a differential and platelet count, were obtained annually through year 10 post-treatment. Study assessments included demographic and baseline characteristics; tumor response, duration of response, survival (progression-free survival \[PFS\] and overall survival \[OS\]), adverse events (AEs), incidence of human anti-murine antibody (HAMA), incidence of hypothyroidism, and serious (fatal and non-fatal) adverse events (SAEs). Dosing;Dosimetric Doses, Intravenous (IV) administration of unlabeled TST (0, 95 or 475 mg) was administered to determine the dose of unlabeled TST that optimized the radiation dose to the tumor. This was followed by 5 mCi of I-131 TST. Serial whole body sodium iodide scintillation probe counts were obtained daily, for at least 5 days, in order to determine the rate of whole body clearance of radioactivity (residence time). The residence time was used to determine the radioactive clearance from the subject and subsequently the activity (in mCi) of Iodine-131 required to deliver the desired TBD of radiation during the therapeutic dose of TST/I-131 TST. Because 475 mg was determined to be the optimal pre-dose of tositumomab in the first subjects entered, the last 34 subjects received a single dosimetric dose that was preceded by an infusion of 475 mg of tositumomab (Source Data: Listing 13). Therapeutic Dose, Groups of 3-6 subjects were treated at successively higher therapeutic whole body radiation doses, beginning at a TBD of 25 cGy. The TBD was escalated in 10 cGy increments in subsequent dose level cohorts until the MTD was achieved. A separate determination of MTD was conducted for subjects who had undergone prior BMT. This was initiated at a TBD of 65 cGy TBD and increased in 10 cGy increments until determination of the MTD. The MTD was defined as the dose at which fewer than 1/3 or 2/6 subjects experienced DLT, i.e. any Grade 4 hematologic toxicity (absolute neutrophil count \[ANC\], platelets, hemoglobin, white blood count \[WBC\] lasting \> 7 days or any Grade 3 hematologic toxicity lasting \> 14 days, as defined in Section 4.1. Re-Dosing; Subjects who achieved tumor regression were considered for re-dosing, using the original therapeutic dose of TST/I-131 TST, at the time the tumor was no longer shrinking in an attempt to upgrade their response. Patients were not redosed sooner than 6 weeks following a therapeutic dose. Retreatment (≥6 weeks following therapeutic dose); Subjects who achieved a PR or CR were considered for retreatment following relapse of their NHL. The original therapeutic dose of TST/I-131 TST was given unless a Grade 2 or greater toxicity had been encountered, in which case the dose level immediately below the original dose was administered.
Interventions
BIOLOGICALRadiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas (Tositumomab and Iodine I 131 Tositumomab)
131-I anti-B1 is the product of 131-I labeling of the anti-CD20 murine monoclonal antibody and the anti-B1 antibody itself is an intact IgG2a murine monoclonal antibody which has specificity far the CD20 antigen on human B cells. Anti-B1 is a clear, colorless liquid. 131-I labeling of the anti-B1 antibody will be carried out by iodogen technique. Trace labeling of the antibody will involve the labeling of approximately 1 to 3 mg of antibody with 5 mCi of 131-I.
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
* Subjects had histologically-confirmed NHL. * Subjects with low-, intermediate-, or high-grade histologies, according to the International Working Formulation. * Subjects had relapsed after or had failed to respond to at least 1 prior chemotherapy regimen. * Subjects had evidence that their tumor tissue expressed the CD20 antigen.
Exclusion criteria
* ≥25% bone marrow involvement. * Absolute granulocyte count ≥1500 cells/mm3 or platelet count ≤100,000 platelets/mm3. * Creatinine ≥2.0 mg/dL, bilirubin ≥2.0 mg/dL. * Cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within 4 weeks of study entry. * Active infection, collagen vascular disease, vasculitis, glomerulonephritis, New York Heart Association class II or IV heart disease and/or serious illness. * Prior external beam radiation therapy such that the maximum tolerated dose level for any normal organ would be exceeded by additional irradiation. * Pregnancy. * Allergy to iodine or previous sensitization to mouse protein as documented by positive anti-mouse antibody ELISA test. * Known brain metastases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | Par. (groups of 3-6) received the TD at a total body dose (TBD) of 25 centiGray (cGy) or 65 cGy (par. who had bone marrow transplantation), increasing by 10 cGy increments at each dose level, until the maximum tolerated dose (MTD) was achieved. The MTD was defined as the highest dose level at which 0/3 or 1/6 par. experienced dose-limiting toxicity (DLT): any Grade 4 hematologic toxicity (National Cancer Institute criteria) lasting \>7 days, any Grade 3 hematologic toxicity lasting \>2 weeks, or any Grade 3/4 nonhematologic toxicity. Not Applicable (NA) indicates that no par. were re-dosed. |
| Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose) | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | Retreatment was administered to participants either at the initial TD of TST/I 131 TST or at a reduced dose if a \>=Grade 2 toxicity had occurred after initial treatment, until the MTD was achieved. The MTD was defined as the highest dose level at which 0/3 or 1/6 participants experienced DLT: any Grade 4 hematologic toxicity (National Cancer Institute criteria) lasting \>7 days, any Grade 3 hematologic toxicity lasting \>2 weeks, or any Grade 3/4 nonhematologic toxicity. Not Applicable (NA) indicates that no participants were re-dosed. |
| Maximum Tolerated Dose (MTD) of TST/I 131 TST Evaluated in the Study | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | Participants who had prior bone marrow transplantation (BMT) initiated TD at 65 cGy TBD, whereas those who had no prior BMT initiated TD at 25 cGy TBD. The MTD was defined as the highest dose level at which 0/3 or 1/6 par. experienced DLT: any Grade 4 hematologic toxicity (National Cancer Institute criteria) lasting \>7 days, any Grade 3 hematologic toxicity lasting \>2 weeks, or any Grade 3/4 nonhematologic toxicity. Not Applicable (NA) indicates that no par. were re-dosed. |
| Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) | Serial anterior and posterior gamma whole body scans were obtained 1 hour after the administration of the dosimetric dose (on Day 0), and then daily for at least 5 days until Day 7 | Serial whole body sodium iodide scintillation probe counts were obtained from participants approximately 1 hour after the administration of the dosimetric dose and then daily for at least 5 days. Gamma camera images of participants were used to calculate the amount of radiation that accumulated in the target tumor and normal organs (tumor/organ dosimetry). Spleen volume may vary based on disease status, and volume correction allows for a comparison of spleen dose across participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression of Disease or Death | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | 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. |
| Overall Survival | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | Overall survival is defined as the time from the treatment start date to the date of death from any cause. |
| Half-life: Initial Half-life (t1/2 Alpha) and Terminal Half-life (t1/2 Beta) of I 131 TST for the Antibody Predose Levels of 0 mg, 95 mg, and 475 mg | Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion. | t1/2 alpha is the estimated initial or alpha phase half-life in a two-compartmental pharmacokinetic model . t1/2 beta is the estimated terminal or beta phase half-life in a two-compartmental pharmacokinetic model; also denoted as t1/2. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half. |
| Clearance (CL) of I 131 TST for the Indicated Antibody Predose Levels | Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion. | Clearance is defined as the volume of blood from which drug is removed per unit time and is a measure of the rate at which drug is removed from the body after the dose. |
| Area Under the Concentration Time Curve (AUC) of I 131 TST for the Indicated Antibody Predose Levels | Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion. | Area under the concentration-time curve from the end of the infusion extrapolated to infinite time. AUC measures how much drug is in the system over time after infusion. ID, injected dose. |
| Maximum Blood Concentration (Cmax) of I 131 TST for the Indicated Antibody Predose Levels | Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion | Cmax is defined as the maximum observed concentration of the drug in blood. |
| Volume of Distribution at Steady State (Vss) of I 131 TST for the Indicated Antibody Predose Levels | Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion | Vss is defined as the volume of distribution of the drug at steady state. |
| Tumor/Organ Dosimetry at the Indicated Predoses of 475 mg, 95 mg, and 0 mg (Initial Treatment) | Serial anterior and posterior gamma whole body scans were obtained 1 hour after the administration of the dosimetric dose (on Day 0), and then daily for at least 5 days until Day 7 | The effect of unlabeled TST pre-treatment on targeting of radioactive TST was evaluated. Serial whole body sodium iodide scintillation probe counts were obtained from participants approximately 1 hour after the administration of the dosimetric dose (DD) and then daily for at least 5 days. Initially, participants received either two or three DDs, each of which was preceded by a pre-dose of unlabeled tositumomab (0, 95, or 475 mg) to determine the dose of unlabeled tositumomab that optimized the radiation dose to tumor. The tumor radiation absorbed dose was determined using gamma camera images. |
| Time to HAMA Positivity From the First Dosimetric Dose (Time From Baseline [Dosimetric Dose] to the First Reported Presence of HAMA) | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | 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 a below threshold level of human anti-mouse antibodies. |
| Number of Participants With the Indicated Type of Infection | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | 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 to Nadir for the Indicated Hematologic Laboratory Parameters | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | Nadir is defined as the lowest laboratory value recorded following the administration of the study medication. |
| Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | Time to recovery to baseline is the time required for recovery from nadir values to baseline values. |
| Nadir Values for the Hematologic Parameters ANC, Platelets, and WBC Count | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | 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 WBC that fights against infection. Platelets and WBCs are types of blood cells. |
| Nadir Values for Hemoglobin, a Hematologic Parameter | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | 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. |
| Number of Participants Who Developed Human Anti-mouse Antibodies (HAMA Postivitiy) After Receiving Tositumomab | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | 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 a below threshold level of human anti-mouse antibodies. |
| Number of Participants (Par.) With the Indicated Response as Assessed by the Investigator | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | Par. with 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 (Par.) With Confirmed Response as Assessed by the Investigator | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | 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 Unconfirmed Responders (CR, CCR, or PR) as Assessed by the Investigator | Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. | Duration of response is defined as the time from the first documented response until disease progression. |
Participant flow
Recruitment details
After an initial treatment (IT), 14 participants (14 of the 59 particpants receiving the IT) who achieved a partial or complete response and subsequently developed progressive disease were retreated (administered at either the initial dose or a reduced dose if a \>=Grade toxicity had occurred after the IT) at the time of disease progression.
Pre-assignment details
Participants received radioimmunotherapy of tositumomab (TST) and Iodine I 131 TST in 2 phases: Phase 1, dosimetric dose; Phase 2, therapeutic dose. After radioimmunotherapy, participants could have entered a 10-year Long-Term Follow-Up study (Study BEX104526; NCT00240591) for continued evaluation.
Participants by arm
| Arm | Count |
|---|---|
| TST and Iodine I 131 TST Participants received 1 to 3 dosimetric doses (DD) consisting of 0, 95, or 475 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine (I 131) TST IV. This was followed by a therapeutic dose (TD) administered 7-14 days after the DD, starting at a total body dose (TBD) of 25 centiGray (cGy) or 65 cGy (only for participants who had undergone bone marrow transplantation) with increments of 10 cGy at each dose level (DL) until the maximum tolerated dose (MTD) was achieved. Participants were re-dosed with a second TD when their tumor stopped regressing (was no longer shrinking). 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. | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Dosimetric and Therapeutic Treatment | Adverse Event | 1 |
| Dosimetric and Therapeutic Treatment | Death | 2 |
| Dosimetric and Therapeutic Treatment | Enrolled in Study BEX104526 | 13 |
| Dosimetric and Therapeutic Treatment | Lost to Follow-up | 1 |
| Dosimetric and Therapeutic Treatment | Progressive Disease | 40 |
| Dosimetric and Therapeutic Treatment | Received Alternate Treatment | 2 |
Baseline characteristics
| Characteristic | TST and Iodine I 131 TST |
|---|---|
| Age, Continuous | 49.9 Years STANDARD_DEVIATION 12.6 |
| Race/Ethnicity, Customized Black | 3 participants |
| Race/Ethnicity, Customized Hispanic | 2 participants |
| Race/Ethnicity, Customized White | 54 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 55 / 59 | 12 / 14 |
| serious Total, serious adverse events | 17 / 59 | 7 / 14 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of TST/I 131 TST Evaluated in the Study
Participants who had prior bone marrow transplantation (BMT) initiated TD at 65 cGy TBD, whereas those who had no prior BMT initiated TD at 25 cGy TBD. The MTD was defined as the highest dose level at which 0/3 or 1/6 par. experienced DLT: any Grade 4 hematologic toxicity (National Cancer Institute criteria) lasting \>7 days, any Grade 3 hematologic toxicity lasting \>2 weeks, or any Grade 3/4 nonhematologic toxicity. Not Applicable (NA) indicates that no par. were re-dosed.
Time frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Maximum Tolerated Dose (MTD) of TST/I 131 TST Evaluated in the Study | Participants who had not undergone BMT | 75 Total body radiation dose in cGy |
| TST and Iodine I 131 TST: Initial Treatment | Maximum Tolerated Dose (MTD) of TST/I 131 TST Evaluated in the Study | Participants who had undergone BMT | 45 Total body radiation dose in cGy |
Primary
Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose)
Retreatment was administered to participants either at the initial TD of TST/I 131 TST or at a reduced dose if a \>=Grade 2 toxicity had occurred after initial treatment, until the MTD was achieved. The MTD was defined as the highest dose level at which 0/3 or 1/6 participants experienced DLT: any Grade 4 hematologic toxicity (National Cancer Institute criteria) lasting \>7 days, any Grade 3 hematologic toxicity lasting \>2 weeks, or any Grade 3/4 nonhematologic toxicity. Not Applicable (NA) indicates that no participants were re-dosed.
Time frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose) | TD=25cGy+Re-dose=NA; Total=25cGy | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose) | TD=35cGy+Re-dose=NA; Total=35cGy | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose) | TD=38cGy+Re-dose=NA; Total=38cGy | 2 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose) | TD=45cGy+Re-dose=NA; Total=45cGy | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose) | TD=45cGy+Re-dose=45cGy; Total=90cGy | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose) | TD=55cGy+Re-dose=NA; Total=55cGy | 2 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose) | TD=60cGy+Re-dose=NA; Total=60cGy | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose) | TD=65cGy+Re-dose=NA; Total=65cGy | 2 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose) | TD=75cGy+Re-dose=NA; Total=75cGy | 3 participants |
Primary
Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose)
Par. (groups of 3-6) received the TD at a total body dose (TBD) of 25 centiGray (cGy) or 65 cGy (par. who had bone marrow transplantation), increasing by 10 cGy increments at each dose level, until the maximum tolerated dose (MTD) was achieved. The MTD was defined as the highest dose level at which 0/3 or 1/6 par. experienced dose-limiting toxicity (DLT): any Grade 4 hematologic toxicity (National Cancer Institute criteria) lasting \>7 days, any Grade 3 hematologic toxicity lasting \>2 weeks, or any Grade 3/4 nonhematologic toxicity. Not Applicable (NA) indicates that no par. were re-dosed.
Time frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: Intent-to-Treat (ITT) Exposed Population: all participants who were enrolled into the study and received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=0cGy+Re-dose=NA; Total=0cGy | 6 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=25cGy+Re-dose=NA; Total=25cGy | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=25cGy+Re-dose=25cGy; Total=50cGy | 2 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=35cGy+Re-dose=NA; Total=35cGy | 4 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=45cGy+Re-dose=NA; Total=45cGy | 8 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=45cGy+Re-dose=45cGy; Total=90cGy | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=55cGy+Re-dose=NA; Total=55cGy | 8 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=65cGy+Re-dose=NA; Total=65cGy | 5 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=65cGy+Re-dose=65cGy; Total 130cGy | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=75cGy+Re-dose=NA; Total=75cGy | 18 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=75cGy+Re-dose=65cGy; Total=140cGy | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=75cGy+Re-dose=75cGy; Total=150cGy | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose) | TD=85cGy+Re-dose=NA; Total=85cGy | 3 participants |
Primary
Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment)
Serial whole body sodium iodide scintillation probe counts were obtained from participants approximately 1 hour after the administration of the dosimetric dose and then daily for at least 5 days. Gamma camera images of participants were used to calculate the amount of radiation that accumulated in the target tumor and normal organs (tumor/organ dosimetry). Spleen volume may vary based on disease status, and volume correction allows for a comparison of spleen dose across participants.
Time frame: Serial anterior and posterior gamma whole body scans were obtained 1 hour after the administration of the dosimetric dose (on Day 0), and then daily for at least 5 days until Day 7
Population: ITT Exposed Population. Of the 59 participants analyzed, 23 received 2 or 3 dosimetric doses (DD); tumor/organ dosimetry was calculated for all 86 DD. The n in the category title reflects the number of DD, which will differ for each target organ depending on whether adequate gamma camera images were available for analysis after each of the 86 DD.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) | Liver (average), n=46 | 261.26 cGy/75 cGy TBD | Standard Deviation 72.03 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) | Lungs (average), n=46 | 192.35 cGy/75 cGy TBD | Standard Deviation 67.53 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) | Spleen (volume-corrected), n=77 | 477.68 cGy/75 cGy TBD | Standard Deviation 235.95 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) | Tumor (average), n=57 | 1074.27 cGy/75 cGy TBD | Standard Deviation 704.8 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) | Kidney (average), n=46 | 607.57 cGy/75 cGy TBD | Standard Deviation 185.66 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) | Urine Bladder Wall (average), n=86 | 242.59 cGy/75 cGy TBD | Standard Deviation 93.24 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) | Bone marrow (average), n=38 | 101.25 cGy/75 cGy TBD | Standard Deviation 16.1 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) | Blood (average), n=42 | 368.60 cGy/75 cGy TBD | Standard Deviation 96.3 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) | Testes (average), n=45 | 58.06 cGy/75 cGy TBD | Standard Deviation 6.14 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment) | Ovaries (average), n=20 | 71.03 cGy/75 cGy TBD | Standard Deviation 4.42 |
Secondary
Area Under the Concentration Time Curve (AUC) of I 131 TST for the Indicated Antibody Predose Levels
Area under the concentration-time curve from the end of the infusion extrapolated to infinite time. AUC measures how much drug is in the system over time after infusion. ID, injected dose.
Time frame: Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion.
Population: ITT Exposed Population. The sample size (n) in the category titles is the number of infusions (dosing occasions) with parameter results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Area Under the Concentration Time Curve (AUC) of I 131 TST for the Indicated Antibody Predose Levels | 475 mg, n=102 | 1.68 %ID * hours per milliliter (%ID.hr/mL) | Standard Deviation 0.74 |
| TST and Iodine I 131 TST: Initial Treatment | Area Under the Concentration Time Curve (AUC) of I 131 TST for the Indicated Antibody Predose Levels | 0 mg, n=24 | 0.838 %ID * hours per milliliter (%ID.hr/mL) | Standard Deviation 0.453 |
| TST and Iodine I 131 TST: Initial Treatment | Area Under the Concentration Time Curve (AUC) of I 131 TST for the Indicated Antibody Predose Levels | 95 mg, n=35 | 1.42 %ID * hours per milliliter (%ID.hr/mL) | Standard Deviation 0.73 |
Secondary
Clearance (CL) of I 131 TST for the Indicated Antibody Predose Levels
Clearance is defined as the volume of blood from which drug is removed per unit time and is a measure of the rate at which drug is removed from the body after the dose.
Time frame: Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion.
Population: ITT Exposed Population. The sample size (n) in the category titles is the number of infusions (dosing occasions) with parameter results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Clearance (CL) of I 131 TST for the Indicated Antibody Predose Levels | 0 mg, n=24 | 205 Milliliters per hour (mL/hr) | Standard Deviation 229 |
| TST and Iodine I 131 TST: Initial Treatment | Clearance (CL) of I 131 TST for the Indicated Antibody Predose Levels | 95 mg, n=35 | 99.4 Milliliters per hour (mL/hr) | Standard Deviation 78.4 |
| TST and Iodine I 131 TST: Initial Treatment | Clearance (CL) of I 131 TST for the Indicated Antibody Predose Levels | 475 mg, n=102 | 72.1 Milliliters per hour (mL/hr) | Standard Deviation 39 |
Secondary
Duration of Response for All Unconfirmed Responders (CR, CCR, or PR) as Assessed by the Investigator
Duration of response is defined as the time from the first documented response until disease progression.
Time frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population. Only those participants with unconfirmed response (CR, CCR, or PR) and those who experienced progressive disease were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Duration of Response for All Unconfirmed Responders (CR, CCR, or PR) as Assessed by the Investigator | 8.5 months |
| TST and Iodine I 131 TST: Retreatment | Duration of Response for All Unconfirmed Responders (CR, CCR, or PR) as Assessed by the Investigator | 7.7 months |
Secondary
Half-life: Initial Half-life (t1/2 Alpha) and Terminal Half-life (t1/2 Beta) of I 131 TST for the Antibody Predose Levels of 0 mg, 95 mg, and 475 mg
t1/2 alpha is the estimated initial or alpha phase half-life in a two-compartmental pharmacokinetic model . t1/2 beta is the estimated terminal or beta phase half-life in a two-compartmental pharmacokinetic model; also denoted as t1/2. Half-life measures how long it takes for the concentration of drug in the blood to decrease by half.
Time frame: Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion.
Population: ITT Exposed Population. The sample size (n) in the category titles is the number of infusions (dosing occasions) with parameter results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Half-life: Initial Half-life (t1/2 Alpha) and Terminal Half-life (t1/2 Beta) of I 131 TST for the Antibody Predose Levels of 0 mg, 95 mg, and 475 mg | 0 mg, t1/2 alpha, n=24 | 6.2 hours (hr) | Standard Deviation 5.7 |
| TST and Iodine I 131 TST: Initial Treatment | Half-life: Initial Half-life (t1/2 Alpha) and Terminal Half-life (t1/2 Beta) of I 131 TST for the Antibody Predose Levels of 0 mg, 95 mg, and 475 mg | 95 mg, t1/2 alpha, n=34 | 6.0 hours (hr) | Standard Deviation 6.5 |
| TST and Iodine I 131 TST: Initial Treatment | Half-life: Initial Half-life (t1/2 Alpha) and Terminal Half-life (t1/2 Beta) of I 131 TST for the Antibody Predose Levels of 0 mg, 95 mg, and 475 mg | 475 mg, t1/2 alpha, n=96 | 6.7 hours (hr) | Standard Deviation 6.8 |
| TST and Iodine I 131 TST: Initial Treatment | Half-life: Initial Half-life (t1/2 Alpha) and Terminal Half-life (t1/2 Beta) of I 131 TST for the Antibody Predose Levels of 0 mg, 95 mg, and 475 mg | 0 mg, terminal t1/2 beta, n=24 | 63.2 hours (hr) | Standard Deviation 51.5 |
| TST and Iodine I 131 TST: Initial Treatment | Half-life: Initial Half-life (t1/2 Alpha) and Terminal Half-life (t1/2 Beta) of I 131 TST for the Antibody Predose Levels of 0 mg, 95 mg, and 475 mg | 95 mg, terminal t1/2 beta, n=35 | 72.6 hours (hr) | Standard Deviation 41.3 |
| TST and Iodine I 131 TST: Initial Treatment | Half-life: Initial Half-life (t1/2 Alpha) and Terminal Half-life (t1/2 Beta) of I 131 TST for the Antibody Predose Levels of 0 mg, 95 mg, and 475 mg | 475 mg, terminal t1/2 beta, n=102 | 84.5 hours (hr) | Standard Deviation 52.9 |
Secondary
Maximum Blood Concentration (Cmax) of I 131 TST for the Indicated Antibody Predose Levels
Cmax is defined as the maximum observed concentration of the drug in blood.
Time frame: Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion
Population: ITT Exposed Population. The sample size (n) in the category titles is the number of infusions (dosing occasions) with parameter results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Maximum Blood Concentration (Cmax) of I 131 TST for the Indicated Antibody Predose Levels | 0 mg, n=24 | 0.0164 % Injected Dose per milliliter (%ID/mL) | Standard Deviation 0.0046 |
| TST and Iodine I 131 TST: Initial Treatment | Maximum Blood Concentration (Cmax) of I 131 TST for the Indicated Antibody Predose Levels | 95 mg, n=35 | 0.0190 % Injected Dose per milliliter (%ID/mL) | Standard Deviation 0.0042 |
| TST and Iodine I 131 TST: Initial Treatment | Maximum Blood Concentration (Cmax) of I 131 TST for the Indicated Antibody Predose Levels | 475 mg, n=102 | 0.0194 % Injected Dose per milliliter (%ID/mL) | Standard Deviation 0.0041 |
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 who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Nadir Values for Hemoglobin, a Hematologic Parameter | 10.9 G/dL |
| TST and Iodine I 131 TST: Retreatment | Nadir Values for Hemoglobin, a Hematologic Parameter | 11.7 G/dL |
Secondary
Nadir Values for the Hematologic Parameters ANC, Platelets, and WBC Count
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 WBC that fights against infection. Platelets and WBCs are types of blood cells.
Time frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population. Only those participants for which nadir could be calculated were analyzed. Some participants did not have post-baseline data available.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Nadir Values for the Hematologic Parameters ANC, Platelets, and WBC Count | ANC, n=40, 12 | 1.0 1000 cells/millimeters cubed (mm^3) |
| TST and Iodine I 131 TST: Initial Treatment | Nadir Values for the Hematologic Parameters ANC, Platelets, and WBC Count | Platelets, n=57, 14 | 74.0 1000 cells/millimeters cubed (mm^3) |
| TST and Iodine I 131 TST: Initial Treatment | Nadir Values for the Hematologic Parameters ANC, Platelets, and WBC Count | WBC count, n=57, 14 | 2.7 1000 cells/millimeters cubed (mm^3) |
| TST and Iodine I 131 TST: Retreatment | Nadir Values for the Hematologic Parameters ANC, Platelets, and WBC Count | ANC, n=40, 12 | 1.3 1000 cells/millimeters cubed (mm^3) |
| TST and Iodine I 131 TST: Retreatment | Nadir Values for the Hematologic Parameters ANC, Platelets, and WBC Count | Platelets, n=57, 14 | 79.5 1000 cells/millimeters cubed (mm^3) |
| TST and Iodine I 131 TST: Retreatment | Nadir Values for the Hematologic Parameters ANC, Platelets, and WBC Count | WBC count, n=57, 14 | 3.3 1000 cells/millimeters cubed (mm^3) |
Secondary
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 who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population. Only those participants evaluable for confirmed response were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator | Confirmed CR | 20 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator | Confirmed CCR | 0 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator | Confirmed PR | 9 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator | Confirmed CR | 4 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator | Confirmed CCR | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator | Confirmed PR | 3 participants |
Secondary
Number of Participants (Par.) With the Indicated Response as Assessed by the Investigator
Par. with 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 who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population. Only those participants evaluable for response were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) With the Indicated Response as Assessed by the Investigator | CR | 20 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) With the Indicated Response as Assessed by the Investigator | CCR | 0 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants (Par.) With the Indicated Response as Assessed by the Investigator | PR | 22 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants (Par.) With the Indicated Response as Assessed by the Investigator | CR | 4 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants (Par.) With the Indicated Response as Assessed by the Investigator | CCR | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants (Par.) With the Indicated Response as Assessed by the Investigator | PR | 4 participants |
Secondary
Number of Participants Who Developed Human Anti-mouse Antibodies (HAMA Postivitiy) After Receiving Tositumomab
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 a below threshold level of human anti-mouse antibodies.
Time frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population. Only those participants evaluable for HAMA were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants Who Developed Human Anti-mouse Antibodies (HAMA Postivitiy) After Receiving Tositumomab | Positive | 9 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants Who Developed Human Anti-mouse Antibodies (HAMA Postivitiy) After Receiving Tositumomab | Negative | 49 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants Who Developed Human Anti-mouse Antibodies (HAMA Postivitiy) After Receiving Tositumomab | Positive | 2 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants Who Developed Human Anti-mouse Antibodies (HAMA Postivitiy) After Receiving Tositumomab | Negative | 2 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 who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Pneumonia Streptococcal; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Nasopharyngitis; n=24, 2 | 2 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Any Infection; n=59, 14 | 24 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | No Infection; n=59, 14 | 35 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Upper Respiratory Tract Infection; n=24, 2 | 6 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Urinary Tract Infection; n=24, 2 | 5 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Respiratory Tract Infection; n=24, 2 | 2 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Sinusitis; n=24, 2 | 2 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Device Related Infection; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Eye Infection; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Hemophilus Infection; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Herpes Virus Infection; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Herpes Zoster; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Infusion Site Cellulitis; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Pneumonia; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Postoperative Wound Infection; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Staphylococcal Sepsis; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Vestibular Neuronitis; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Viral Infection; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Viral Upper Respiratory Tract Infection; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Initial Treatment | Number of Participants With the Indicated Type of Infection | Sepsis; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Vestibular Neuronitis; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Pneumonia Streptococcal; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Sepsis; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Hemophilus Infection; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Nasopharyngitis; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Postoperative Wound Infection; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Any Infection; n=59, 14 | 2 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Herpes Virus Infection; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | No Infection; n=59, 14 | 12 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Viral Upper Respiratory Tract Infection; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Upper Respiratory Tract Infection; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Herpes Zoster; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Urinary Tract Infection; n=24, 2 | 1 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Staphylococcal Sepsis; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Respiratory Tract Infection; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Infusion Site Cellulitis; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Sinusitis; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Viral Infection; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Device Related Infection; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Pneumonia; n=24, 2 | 0 participants |
| TST and Iodine I 131 TST: Retreatment | Number of Participants With the Indicated Type of Infection | Eye Infection; n=24, 2 | 0 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 who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
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: Initial Treatment | Overall Survival | 46.4 months |
| TST and Iodine I 131 TST: Retreatment | Overall Survival | 45.0 months |
Secondary
Time to HAMA Positivity From the First Dosimetric Dose (Time From Baseline [Dosimetric Dose] to the First Reported Presence of HAMA)
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 a below threshold level of human anti-mouse antibodies.
Time frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population. Participants who converted to HAMA positivity were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Time to HAMA Positivity From the First Dosimetric Dose (Time From Baseline [Dosimetric Dose] to the First Reported Presence of HAMA) | 15.0 days |
| TST and Iodine I 131 TST: Retreatment | Time to HAMA Positivity From the First Dosimetric Dose (Time From Baseline [Dosimetric Dose] to the First Reported Presence of HAMA) | 1271 days |
Secondary
Time to Nadir for the Indicated Hematologic Laboratory Parameters
Nadir is defined as the lowest laboratory value recorded following the administration of the study medication.
Time frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population. Only those participants for which nadir could be calculated were analyzed. Some participants did not have post-baseline data available.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Time to Nadir for the Indicated Hematologic Laboratory Parameters | Time to nadir, ANC, n=40, 12 | 44.5 days |
| TST and Iodine I 131 TST: Initial Treatment | Time to Nadir for the Indicated Hematologic Laboratory Parameters | Time to nadir, hemoglobin, n=57, 14 | 34.0 days |
| TST and Iodine I 131 TST: Initial Treatment | Time to Nadir for the Indicated Hematologic Laboratory Parameters | Time to nadir, platelets, n=57, 14 | 34.0 days |
| TST and Iodine I 131 TST: Initial Treatment | Time to Nadir for the Indicated Hematologic Laboratory Parameters | Time to nadir, WBC count, n=57, 14 | 41.0 days |
| TST and Iodine I 131 TST: Retreatment | Time to Nadir for the Indicated Hematologic Laboratory Parameters | Time to nadir, WBC count, n=57, 14 | 48.0 days |
| TST and Iodine I 131 TST: Retreatment | Time to Nadir for the Indicated Hematologic Laboratory Parameters | Time to nadir, ANC, n=40, 12 | 44.5 days |
| TST and Iodine I 131 TST: Retreatment | Time to Nadir for the Indicated Hematologic Laboratory Parameters | Time to nadir, platelets, n=57, 14 | 41.0 days |
| TST and Iodine I 131 TST: Retreatment | Time to Nadir for the Indicated Hematologic Laboratory Parameters | Time to nadir, hemoglobin, n=57, 14 | 49.5 days |
Secondary
Time to Progression of Disease or Death
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.
Time frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population. Only those participants who experienced progression were evaluated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Time to Progression of Disease or Death | 5.7 months |
| TST and Iodine I 131 TST: Retreatment | Time to Progression of Disease or Death | 4.9 months |
Secondary
Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters
Time to recovery to baseline is the time required for recovery from nadir values to baseline values.
Time frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.
Population: ITT Exposed Population. Only those participants for which nadir could be calculated were analyzed. Some participants did not have post-baseline data available.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters | Time to recovery to baseline, ANC, n=23, 2 | 79.0 days |
| TST and Iodine I 131 TST: Initial Treatment | Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters | Time to recovery to baseline, hemoglobin, n=46, 4 | 42.0 days |
| TST and Iodine I 131 TST: Initial Treatment | Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters | Time to recovery to baseline, platelets, n=45, 4 | 57.0 days |
| TST and Iodine I 131 TST: Initial Treatment | Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters | Time to recovery to baseline, WBC count, n=46, 3 | 69.0 days |
| TST and Iodine I 131 TST: Retreatment | Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters | Time to recovery to baseline, WBC count, n=46, 3 | 77.0 days |
| TST and Iodine I 131 TST: Retreatment | Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters | Time to recovery to baseline, ANC, n=23, 2 | 74.0 days |
| TST and Iodine I 131 TST: Retreatment | Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters | Time to recovery to baseline, platelets, n=45, 4 | 39.0 days |
| TST and Iodine I 131 TST: Retreatment | Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters | Time to recovery to baseline, hemoglobin, n=46, 4 | 38.5 days |
Secondary
Tumor/Organ Dosimetry at the Indicated Predoses of 475 mg, 95 mg, and 0 mg (Initial Treatment)
The effect of unlabeled TST pre-treatment on targeting of radioactive TST was evaluated. Serial whole body sodium iodide scintillation probe counts were obtained from participants approximately 1 hour after the administration of the dosimetric dose (DD) and then daily for at least 5 days. Initially, participants received either two or three DDs, each of which was preceded by a pre-dose of unlabeled tositumomab (0, 95, or 475 mg) to determine the dose of unlabeled tositumomab that optimized the radiation dose to tumor. The tumor radiation absorbed dose was determined using gamma camera images.
Time frame: Serial anterior and posterior gamma whole body scans were obtained 1 hour after the administration of the dosimetric dose (on Day 0), and then daily for at least 5 days until Day 7
Population: ITT Exposed Population. Participants who received unlabelled doses of 0 mg, 95 mg, or 475 mg were analyzed. Of the 59 participants analyzed, 23 received 2 or 3 dosimetric doses (DD); tumor/organ dosimetry was calculated for all 86 DD. The n in the category title reflects the number of DD, which will differ for each target organ.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry at the Indicated Predoses of 475 mg, 95 mg, and 0 mg (Initial Treatment) | 475 mg Predose, Tumor (average); n=28 | 1023.04 cGy/75 cGy TBD | Standard Deviation 711.44 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry at the Indicated Predoses of 475 mg, 95 mg, and 0 mg (Initial Treatment) | 475 mg Predose, Spleen (volume-corrected); n=36 | 411.5 cGy/75 cGy TBD | Standard Deviation 217.4 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry at the Indicated Predoses of 475 mg, 95 mg, and 0 mg (Initial Treatment) | 95 mg Predose, Spleen (volume-corrected); n=21 | 451.77 cGy/75 cGy TBD | Standard Deviation 238.4 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry at the Indicated Predoses of 475 mg, 95 mg, and 0 mg (Initial Treatment) | 95 mg Predose, Tumor (average); n=14 | 1177.3 cGy/75 cGy TBD | Standard Deviation 650.3 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry at the Indicated Predoses of 475 mg, 95 mg, and 0 mg (Initial Treatment) | 0 mg, Spleen (volume-corrected); n=20 | 624 cGy/75 cGy TBD | Standard Deviation 210.26 |
| TST and Iodine I 131 TST: Initial Treatment | Tumor/Organ Dosimetry at the Indicated Predoses of 475 mg, 95 mg, and 0 mg (Initial Treatment) | 0 mg, Tumor (average); n=15 | 1073.75 cGy/75 cGy TBD | Standard Deviation 776.1 |
Secondary
Volume of Distribution at Steady State (Vss) of I 131 TST for the Indicated Antibody Predose Levels
Vss is defined as the volume of distribution of the drug at steady state.
Time frame: Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion
Population: ITT Exposed Population. The sample size (n) in the category titles is the number of infusions (dosing occasions) with parameter results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TST and Iodine I 131 TST: Initial Treatment | Volume of Distribution at Steady State (Vss) of I 131 TST for the Indicated Antibody Predose Levels | 0 mg, n=24 | 13.0 liters | Standard Deviation 12.3 |
| TST and Iodine I 131 TST: Initial Treatment | Volume of Distribution at Steady State (Vss) of I 131 TST for the Indicated Antibody Predose Levels | 95 mg, n=35 | 7.74 liters | Standard Deviation 4.25 |
| TST and Iodine I 131 TST: Initial Treatment | Volume of Distribution at Steady State (Vss) of I 131 TST for the Indicated Antibody Predose Levels | 475 mg, n=102 | 7.08 liters | Standard Deviation 2.16 |