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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00268203
First received: December 20, 2005
Last updated: March 20, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma, Non-Hodgkin
Biological: Iodine I 131 Tositumomab Therapeutic Regimen
Phase 2

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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With Unconfirmed Response (Complete Response or Partial Response) and Unconfirmed Complete Response [ Time Frame: From randomization until the first documented complete response or partial response (up to 161 months) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Confirmed Response (Complete Response or Partial Response) and Confirmed Complete Response [ Time Frame: From randomization until the first documented complete response or partial response (up to 161 months) ] [ Designated as safety issue: No ]
    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.

  • Duration of Response for Participants With Unconfirmed Response (CR+PR) [ Time Frame: From the time of the first documented response (CR or PR) until disease progression (up to 161 months) ] [ Designated as safety issue: No ]
    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.

  • Duration of Response for Participants With Confirmed Response (CR+PR) [ Time Frame: From the time of the first documented response (CR or PR) until disease progression (up to 161 months) ] [ Designated as safety issue: No ]
    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.

  • Duration of Response (DOR) in Unconfirmed Complete Responders [ Time Frame: From the time of the first documented unconfirmed CR until PD (up to 161 months) ] [ Designated as safety issue: No ]
    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.

  • Duration of Response (DOR) in Confirmed Complete Responders [ Time Frame: From the time of the first documented CR until PD (up to 161 months) ] [ Designated as safety issue: No ]
    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.

  • Time to Progression or Death [ Time Frame: From the treatment start date to the first documented incidence of disease progression (PD) or death (up to 161 months) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to Treatment Failure [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 765
Study Start Date: September 1998
Study Completion Date: February 2013
Primary Completion Date: March 2000 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Iodine I 131 Tositumomab Therapeutic Regimen
    Patients will receive unlabeled Tositumomab (450 mg) followed by Tositumomab (35 mg) which has been trace-labeled with 5 mCi of Iodine-131 (dosimetric dose). Whole body counts using a gamma camera will be obtained 3 times between Days 0 and 7 following the dosimetric dose to determine a patient-specific mCi dose of Iodine-131 calculated to deliver the desired total body dose of radiation (either 65 cGy or 75 cGy). The therapeutic dose is administered 7-14 days after the dosimetric dose. Patients will receive unlabeled Tositumomab (450 mg) followed by Tositumomab (35 mg) labeled with the patient-specific dose of Iodine-131 (median dose in previous studies was approximately 85 mCi). Patients who are obese will be dosed based upon 137% of their calculated lean body mass. Patients will be treated with thyroid blocking medication at least 24 hours prior to the dosimetric dose and continuing for 14 days following the therapeutic dose.
    Other Name: Iodine I 131 Tositumomab Therapeutic Regimen
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00268203

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00268203     History of Changes
Other Study ID Numbers: BEX104545, EAP CP-98-020
Study First Received: December 20, 2005
Results First Received: October 10, 2013
Last Updated: March 20, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Switzerland: Federal Office of Public Health
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
expanded access study
refractory low-grade non-Hodgkin's Lymphoma
Bexxar®
Iodine I 131 Tositumomab
EAP
relapsed low-grade non-Hodgkin's lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Iodine
Cadexomer iodine
Iodine-131 anti-B1 antibody
Antibodies, Monoclonal
Anti-Infective Agents, Local
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents
Immunologic Factors

ClinicalTrials.gov processed this record on October 19, 2014