Rituximab in Treating Patients With Follicular Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving rituximab over a short period of time is more effective than giving it over a long period of time in treating follicular non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is studying rituximab to see how well it works when given over a short period of time compared to when given over a long period of time in treating patients with follicular non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Compare the efficacy of induction therapy with rituximab followed by short- vs long-term maintenance therapy with rituximab, in terms of event-free survival, in patients with follicular non-Hodgkin's lymphoma. Secondary Compare the safety of these regimens in these patients. Compare the pharmaeconomical aspects of these regimens in these patients. Compare the evolution of immunologic competence in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Induction therapy: Patients receive rituximab IV weekly in weeks 1-4 and undergo restaging between weeks 11-13. Patients with stable disease or progressive disease are taken off study. Patients achieving partial or complete response are stratified according to prior treatment status (untreated* vs treated with or without anti-CD20 therapy), presence of bulky disease** at study entry (yes vs no), and participating center. Patients are then randomized to 1 of 2 maintenance treatment arms. NOTE: *Patients treated with radiotherapy only are considered as therapy-naïve. NOTE: **Defined as a mass or lymph node conglomerate ≥ 5 cm diameter. Maintenance therapy: Patients start maintenance therapy within 7 days of randomization. Arm I: Patients receive rituximab IV every 2 months for 4 treatments. Arm II: Patients receive rituximab IV every 2 months for up to 5 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression or relapse and then annually for up to 10 years after randomization. PROJECTED ACCRUAL: A total of 270 patients will be accrued for this study within 3 years.

Official Title
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Comparing Two Schedules of Rituximab Maintenance in Rituximab-Responding Patients With Untreated, Chemotherapy Resistant or Relapsed Follicular Lymphoma: A Randomized Phase III Trial

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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DISEASE CHARACTERISTICS: Histologically confirmed follicular lymphoma Grade 1, 2, 3a, or 3b disease by WHO staging system CD20-positive by immunohistochemistry Previously untreated disease OR meets 1 of the following criteria for response to prior treatment: Chemotherapy-resistant disease Relapsed or progressive disease Stable disease At least 12 weeks since prior systemic treatment At least 1 bidimensionally measurable lesion ≥ 11 mm by CT scan or MRI No transformation to high-grade lymphoma secondary to low-grade follicular lymphoma No prior or current CNS disease (i.e., CNS lymphoma or lymphomatous meningosis) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of indolent or aggressive lymphoma will replace the former terminology of low, intermediate, or high grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age 18 and over Performance status WHO 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Cardiovascular Ejection fraction ≥ 50% by echocardiography or MUGA Immunologic No acute or ongoing infection No HIV infection No active autoimmune disease Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 12 months after completion of the study treatment No uncontrolled diabetes mellitus No other medical condition that would preclude study participation No other malignancy except nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix No other condition (e.g., geographic proximity) that would preclude study compliance and follow-up PRIOR CONCURRENT THERAPY: Biologic therapy See Radiotherapy Prior rituximab allowed Chemotherapy See Disease Characteristics Endocrine therapy More than 4 weeks since prior regular administration of corticosteroids Dose equivalent to ≤ 20 mg/day prednisone allowed for conditions other than lymphoma or lymphoma-related symptoms No concurrent corticosteroids for prevention or treatment of side effects except acute life-threatening side effects Radiotherapy Prior radiolabeled anti-CD20 therapy (administered alone or in combination with cytostatic drugs) allowed provided patient has achieved partial or complete response after the therapy At least 12 months since prior anti-CD20 therapy Surgery Not specified Other More than 30 days since prior systemic tumor therapy More than 30 days since prior participation in another clinical trial No other concurrent anticancer therapy

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 every 2 months x4<br>Rituximab 375 mg/m2 every 2 months x4 | Biological: rituximab<br>* comparing two maintenance schedules of Rituximab<br>* Other names: MABTHERA;|
| Active Comparator: Arm B: Rituximab (5 years)<br>Rituximab 375 mg/m2 every 2 months for 5 years or until PD, relapse or unacceptable toxicity | Biological: rituximab<br>* comparing two maintenance schedules of Rituximab<br>* Other names: MABTHERA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival |  | at 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | at 10 years | 
| Overall survival |  | at 10 years | 
| Adverse reactions during and after maintenance treatment |  | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage I grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II grade 3 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma