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Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas

Phase 1

Lymphoma, Non-Hodgkin | Monoclonal antibody | Oncology |GSK plc|Last Updated: Aug 31, 2017

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Trial Design

UNCONTROLLEDDMC
Total Trials1
Total Enrollment59

FDA Designations

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Clinical trial landscape

Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas · 1 trial · 1 indication

Phase 1 1
NCT01536561Study of Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas and Extended Study to Determine the Safety and Efficacy of Coulter Clone® 131Iodine-B1 Radioimmunotherapy of Advanced Non-Hodgkin's LymphomaLymphoma, Non-Hodgkin
COMPLETED59 Analytics
PHASE1COMPLETED
Study of Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas and Extended Study to Determine the Safety and Efficacy of Coulter Clone® 131Iodine-B1 Radioimmunotherapy of Advanced Non-Hodgkin's Lymphoma
Lymphoma, Non-HodgkinUnlock trial analytics

Study Endpoints

Primary Endpoints

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 Endpoints

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
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.
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.
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
open-label, dose escalationEXPERIMENTALEach subject will undergo two phases of study. The first phase, termed "tracer Study", involves the injection of low-radioactivity doses (about 5 mCi) of 131-I anti-B1 for the purposes of determining the rate of whole body clearance of radiation so that a whole body radiation can be calculated. The calculated whole-body radiation dose per mCi administered can then be used to determined how many mCi will be required to deliver a specified whole-body radiation dose in the second phase of the study for each patient, termed radio-immunotherapy dose in a tracer-projected whole-body radiation dose will be used for dose escalation with a minimum of three subjects per dose level.

Interventions

NameTypeDescription
Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas (Tositumomab and Iodine I 131 Tositumomab)BIOLOGICAL131-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.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo

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 evidenc...

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