Expanded Access Study Of BEXXAR® For Low Grade And Transformed Low-Grade Non-Hodgkin's Lymphoma

Expanded Access Study of Iodine I 131 Tositumomab for Relapsed/Refractory Low-Grade and Transformed Low-Grade Non-Hodgkin's Lymphoma

This is a single arm, multi-center, expanded access study of Iodine I 131 Tositumomab (BEXXAR) therapeutic regimen for patients with relapsed or refractory low-grade or transformed low-grade non-Hodgkin's B-cell lymphoma. The primary objective is to make Iodine I 131 Tositumomab more broadly available to patients. Secondary endpoints will be to obtain additional safety and efficacy information for this treatment regimen. Post study drug administration follow-ups will continue for up to ten years. These will include blood-work and adverse event assessments for 13 weeks post dosing, patient response evaluations at Week 13, Months 6, 12, 18, 24, and Long-Term Follow-ups every 6 months until the elapse of 5 years from the dosimetric dose and then annually thereafter through year 10. Thyroid function will be monitored annually during Long-term follow-up.

Study Overview

• Status: Completed
• Conditions: Lymphoma, Non-Hodgkin
• Intervention / Treatment: Biological: Iodine I 131 Tositumomab Therapeutic Regimen

• Study Type: Interventional
• Enrollment (Actual): 765
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of low- grade NHL or transformed low-grade NHL (tumor must be CD 20 positive).
• Prior treatment with at least one chemotherapy regimen and have relapsed or progressed, or failed to achieve an objective response on last chemotherapy regimen.
• Karnofsky performance status of at least 60% and anticipated survival of at least 3 months.
• Absolute granulocyte of >/= 1,500/mm3.
• Platelet count of >/= 100,000/mm3, and not require sustained support of hematopoietic cytokines, or transfusion of blood products.
• Adequate renal function (i.e., <1.5x Upper Limit of Normal), and hepatic transaminases (AST <5 times ULN).
• Signed IRB/IEC-approved informed consent.

Exclusion Criteria:

• Patients with a mean of >25% of the intratrabecular marrow space involved with lymphoma.
• Patients who received cytotoxic chemotherapy, radiation therapy, immunotherapy, or cytokine treatment within 4 weeks prior to study entry (6 weeks for nitrosurea compounds) or who exhibit persistent clinical evidence of toxicity.
• Patients who have undergone stem cell or bone marrow transplant, active obstructive hydronephrosis, active infection, New York Heart Association Class III or IV heart disease or other serious illness that would preclude evaluation.
• Known HIV infection.
• Pregnant or nursing patients.
• Patients with prior malignancy other than lymphoma, except for adequately-treated skin cancer, in-situ cervical cancer, or cancer for which the patient has been disease-free for 5 years.
• Patients with progressive disease within 1 year of irradiation arising in a field that has been previously irradiated with more than 3500 cGy.
• Patients who received prior radioimmunotherapy, known brain or leptomeningeal metastases, HAMA positivity.
• Patients who are receiving either approved or non-approved (through another protocol) anti-cancer drugs or biologics.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Unconfirmed Response (Complete Response or Partial Response) and Unconfirmed Complete Response	A participant was defined as a responder if he/she sustained a complete response (CR: the disappearance of all detectable clinical and radiographic evidence of disease and all disease-related symptoms) or partial response (PR: greater than or equal to a 50% decrease in the sum of the product of perpendicular diameter [SPPD] determined at Baseline; no increase in the size of the other nodes, liver, or spleen; no new sites of disease). Response was evaluated by an investigator per guidelines developed by The International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma.	From randomization until the first documented complete response or partial response (up to 161 months)
Number of Participants With Confirmed Response (Complete Response or Partial Response) and Confirmed Complete Response	A participant was defined as a responder if he/she sustained a complete response (CR: the disappearance of all detectable clinical and radiographic evidence of disease and all disease-related symptoms) or partial response (PR: greater than or equal to a 50% decrease in the sum of the product of perpendicular diameter [SPPD] determined at Baseline; no increase in the size of the other nodes, liver, or spleen; no new sites of disease). Response was evaluated by an investigator per guidelines developed by The International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma. A confirmed response (CR and PR) requires that the response be confirmed by another response (same or better) at least 4 weeks apart.	From randomization until the first documented complete response or partial response (up to 161 months)
Duration of Response for Participants With Unconfirmed Response (CR+PR)	Duration of response is defined as the time from the first documented CR (the disappearance of all detectable clinical and radiographic evidence of disease and all disease-related symptoms) or PR (greater than or equal to a 50% decrease in the SPPD determined at Baseline; no increase in the size of the other nodes, liver, or spleen; no new sites of disease) until disease progression (PD). PD is defined as greater than or equal to a 50% increase from nadir in the SPPD for all measurable disease. Lesion changes believed to represent measurement variation associated with radiographic technique should not be classified as PD. Response was evaluated by an investigator per guidelines developed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma.	From the time of the first documented response (CR or PR) until disease progression (up to 161 months)
Duration of Response for Participants With Confirmed Response (CR+PR)	Duration of response is defined as the time from the first documented CR (the disappearance of all detectable clinical and radiographic evidence of disease and all disease-related symptoms) or PR (greater than or equal to a 50% decrease in the SPPD determined at Baseline; no increase in the size of the other nodes, liver, or spleen; no new sites of disease) until disease progression (PD). PD is defined as greater than or equal to a 50% increase from nadir in the SPPD for all measurable disease. Lesion changes believed to represent measurement variation associated with radiographic technique should not be classified as PD. Response was evaluated by an investigator per guidelines developed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma. A confirmed response (CR and PR) requires that the response be confirmed by another response (same or better) at least 4 weeks apart.	From the time of the first documented response (CR or PR) until disease progression (up to 161 months)
Duration of Response (DOR) in Unconfirmed Complete Responders	DOR is defined as the time from the first documented response to the first documented disease progression. Unconfirmed CR is defined as the disappearance of all detectable clinical and radiographic evidence of disease and all disease-related symptoms. Response was evaluated by an investigator per guidelines developed by The International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphoma.	From the time of the first documented unconfirmed CR until PD (up to 161 months)
Duration of Response (DOR) in Confirmed Complete Responders	DOR is defined as the time from the first documented response to the first documented disease progression. CR is defined as the disappearance of all detectable clinical and radiographic evidence of disease and all disease-related symptoms. A confirmed response (CR and PR) requires that the response be confirmed by another response (same or better) at least 4 weeks apart.	From the time of the first documented CR until PD (up to 161 months)
Time to Progression or Death	Time to progression is defined as the time from the treatment start date to the first documented incidence of disease progression (PD) or death. PD is defined as greater than or equal to a 50% increase from nadir in the SPPD for all measurable disease. Lesion changes believed to represent measurement variation associated with radiographic technique should not be classified as PD.	From the treatment start date to the first documented incidence of disease progression (PD) or death (up to 161 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Treatment Failure	Time to treatment failure is defined as the time from the date of the dosimetric dose to the first occurrence of the following: treatment withdrawal, decision to seek additional therapy, study removal, disease progression, receipt of alternative therapy for lymphoma, or death study withdrawal for any reason. Participants withdrawn for reasons other than progression or death were censored at their date of withdrawal.	From the dosimetric dose to the first occurrence of the following: treatment withdrawal, decision to seek additional therapy, study removal, disease progression, receipt of alternative therapy, or death (up to 161 months)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: September 1, 1998
• Primary Completion (Actual): March 1, 2000
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: December 20, 2005
• First Submitted That Met QC Criteria: December 21, 2005
• First Posted (Estimate): December 22, 2005

Study Record Updates

• Last Update Posted (Estimate): January 9, 2017
• Last Update Submitted That Met QC Criteria: November 18, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Iodine I 131 Tositumomab; EAP; expanded access study; refractory low-grade non-Hodgkin's Lymphoma; Bexxar®; relapsed low-grade non-Hodgkin's lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Antineoplastic Agents; Tositumomab I-131
• Other Study ID Numbers: BEX104545

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Annotated Case Report Form
   Information identifier: BEX104545
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: BEX104545
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: BEX104545
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: BEX104545
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register