Last updated: 11/07/2018 00:31:21

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

Request patient level data
GSK study ID
104728
See study documents
Clinicaltrials.gov ID
NCT01536561
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: Phase I Study of Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas
Trial 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 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:

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)

Timeframe: 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 during retreatment exposed to the indicated dose levels of the TD, re-dose, and total dose (TD + re-dose)

Timeframe: 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.

Maximum tolerated dose (MTD) of TST/I 131 TST evaluated in the study

Timeframe: 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.

Tumor/Organ Dosimetry of TST/I 131 TST for all predoses (Initial Treatment)

Timeframe: 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

Secondary outcomes:

Tumor/Organ Dosimetry at the indicated predoses of 475 mg, 95 mg, and 0 mg (Initial Treatment)

Timeframe: 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

Timeframe: 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

Timeframe: 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 for all unconfirmed responders (CR, CCR, or PR) as assessed by the Investigator

Timeframe: 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 of disease or death

Timeframe: 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

Timeframe: 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.

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

Timeframe: 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 (CL) of I 131 TST for the indicated antibody predose levels

Timeframe: 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 (AUC) of I 131 TST for the indicated antibody predose levels

Timeframe: 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.

Maximum blood concentration (Cmax) of I 131 TST for the indicated antibody predose levels

Timeframe: 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

Volume of distribution at steady state (Vss) of I 131 TST for the indicated antibody predose levels

Timeframe: 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

Number of participants who developed human anti-mouse antibodies (HAMA postivitiy) after receiving tositumomab

Timeframe: 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 HAMA positivity from the first dosimetric dose (time from baseline [dosimetric dose] to the first reported presence of HAMA)

Timeframe: 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 with the indicated type of infection

Timeframe: 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 nadir for the indicated hematologic laboratory parameters

Timeframe: 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 for the indicated hematologic laboratory parameters

Timeframe: 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 values for the hematologic parameters ANC, platelets, and WBC count

Timeframe: 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 values for hemoglobin, a hematologic parameter

Timeframe: 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.

Interventions:
  • Biological/vaccine: Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas (Tositumomab and Iodine I 131 Tositumomab)
    • Enrollment:
    59
    Primary completion date:
    1997-02-07
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Kaminski MS, Estes J, Zasadny KR, Francis IR, Ross CW, Tuck M, Regan D, Fisher S, Gutierrez J, Kroll S, Stagg R, Tidmarsh G, Wahl RL. Radioimmunotherapy with iodine I 131 Tositumomab for relapsed or refractory B-cell non-Hodgkin’s Lymphoma: updated results and long-term follow-up of the University of Michigan experience. Blood 2000;96:1259-1266.
    Medical condition
    Lymphoma, Non-Hodgkin
    Product
    tositumomab
    Collaborators
    Not applicable
    Study date(s)
    April 1990 to October 2009
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Inclusion Criteria
    • Subjects had histologically-confirmed NHL.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • 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.

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    1997-02-07
    Actual study completion date
    2009-16-10

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Participate in clinical trial
    Additional information
    Results for study 104728 can be found on the GSK Clinical Study Register.
    Click here
    Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
    Click here
    Access to clinical trial data by researchers
    Visit website