Rituximab in Treating Patients With Low Tumor Burden Indolent Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known which rituximab regimen is more effective in treating indolent non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and comparing them to see how well they work in treating patients with low tumor burden indolent stage III non-Hodgkin's lymphoma or stage IV non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary To compare time to rituximab failure between the rituximab scheduled and rituximab retreatment arms. Secondary To compare the time to first cytotoxic therapy between the rituximab scheduled and rituximab retreatment arms. To document the rationale for beginning cytotoxic therapy; defined as chemotherapy, radiation therapy or radioimmunotherapy. To compare the toxicities associated with rituximab therapy between the two randomized treatment arms. Quality of Life Objectives: To compare health-related quality of life, distress, psychological functioning, physical well-being and functional well-being of patients receiving rituximab scheduled to those receiving rituximab retreatment. To examine the impact of differential treatment response (delayed time to rituximab failure and/or time to first cytotoxic therapy), if observed, on quality of life, distress, and psychological functioning on patients receiving rituximab scheduled to those receiving rituximab retreatment. To obtain prospective data on physical and functional well-being during treatment with rituximab. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histologic subtype (follicular vs other), age (under 60 vs 60 and over), and the time from diagnosis (less than 1 year vs at least 1 year). Induction rituximab: Patients receive rituximab Intravenous (IV) once a week for 4 weeks. Patients are re-evaluated 9 weeks after the completion of induction rituximab. Patients with a partial or complete response to induction rituximab are randomized to 1 of 2 treatment arms. Arm A (retreatment rituximab): Patients receive rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months. Arm B (scheduled rituximab): Patients receive a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity. Quality of life is assessed after induction rituximab treatment and at 26, 39, 65, 117, 169, and 221 weeks after randomization. Patients are followed at least annually for 15 years from study entry.

Official Title
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Randomized Phase III Trial Comparing Two Different Rituximab Dosing Regimens For Patients With Low Tumor Burden Indolent Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Histologically confirmed non-Hodgkin's lymphoma, including 1 of the following: Follicular grade 1 or 2 Small lymphocytic Marginal zone (nodal) Marginal zone (splenic) Mucosa-associated lymphoid tissue (MALT) Stage III or IV disease Must meet the following criteria for low tumor burden: No nodal or extranodal mass at least 7 cm Less than 3 nodal masses greater than 3 cm in diameter No systemic symptoms or B symptoms No splenomegaly greater than 16 cm by a computed tomography (CT) scan No evidence of risk of compression of a vital organ (i.e., ureteral or epidural) No leukemic phase with greater than 5,000/mm^3 circulating lymphocytes No cytopenias, defined as any of the following: Platelet count less than 100,000/mm^3 Hemoglobin less than 10 g/dL Absolute neutrophil count less than 1,500/mm^3 At least 1 objective measurable disease parameter Abnormal positron emission tomography (PET) scans will not constitute evaluable disease unless verified by CT scan or other appropriate imaging Age: 18 and over Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Must meet the following criteria for labs: Hematopoietic Absolute neutrophil count at least 1,500/mm^3* Hemoglobin at least 10 g/dL* Platelet count at least 100,000/mm^3* NOTE: *Without growth factor and/or transfusion support Hepatic Bilirubin no greater than 2 times upper limit of normal (ULN) OR direct bilirubin normal for patients with Gilbert's Syndrome The aspartate transaminase (AST) and alanine transaminase (ALT) ratio (AST/ALT) no greater than 5 times ULN Hepatitis B surface antigen negative Renal Creatinine no greater than 2 times ULN EXCLUSION CRITERIA: Evidence of transformation to a large cell histology Pregnant or nursing. Fertile patients must use effective contraception HIV positive Uncontrolled active infection Other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix Prior immunotherapy for lymphoma Prior chemotherapy for lymphoma Concurrent chemotherapy Prior radiotherapy for lymphoma Concurrent radiotherapy Concurrent radioimmunotherapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A: Rituximab Retreatment<br>Patients receive rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months. | Biological: rituximab<br>* Given IV<br>|
| Experimental: Arm B: Rituximab Scheduled<br>Patients receive a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity. | Biological: rituximab<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Rituximab Failure (TTRF) | TTRF is defined as the time from randomization until any one of the following criteria are met, and censored at last disease assessment for cases who have not experienced failure (with the cut-off date for final analysis of 11/1/2011): 1. No response (partial response (PR) or complete response (CR)) to rituximab retreatment (Arm A treatment). 2. Time to progression < 26 weeks from day 1 of most recent rituximab treatment. 3. Initiation of alternative therapy. 4. Inability to complete protocol therapy (due to adverse events, patient preference, or any other reason, including death). | Assessed (by restaging CT scans) 26 weeks ± 2 weeks from each rituximab treatment (including induction), counting the first rituximab dose as Day 1, until rituximab failure observed or July 17, 2013, whichever occurred first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Cytotoxic Therapy (TTFC) | TTFC is defined as the time from randomization to the time of first cytotoxic therapy (chemo and radio therapy), and censored as last follow-up time if no cytotoxic therapy has been used. Since median TTFC was not reached in 3 out of the 4 groups, 3-year TTFC was reported which was defined as the probability of not starting first cytotoxic therapy at 3 years. | Assessed every 13 weeks until rituximab failure observed or August 2013, whichever occurred first. | 
| Overall Health-related Quality of Life (HRQL) at 6 Month After Randomization | The overall HRQL was measured by the change in Functional Assessment of Cancer Therapy - General (FACT-G) from baseline to 6 months after randomization. The FACT-G is a 27-item assessment used to measure HRQL, specifically, physical, functional, social and emotional well-being. The total score ranges from 0 to 108, with higher scores indicating better HRQL. | Assessed at baseline and 6 months after randomization. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage III small lymphocytic lymphoma, stage III marginal zone lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma