Combination Chemotherapy Plus Filgrastim With or Without Rituximab in Treating Older Patients With Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells. It is not yet known if combination chemotherapy plus filgrastim is more effective with or without rituximab in treating non-Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to determine the effectiveness of combination chemotherapy plus filgrastim with or without rituximab in treating older patients who have non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), and filgrastim (G-CSF) with or without rituximab on event-free survival of elderly patients with intermediate or high-risk non-Hodgkin's lymphoma. Compare the complete remission rate, overall survival, and disease-free survival of patients treated with these regimens. Compare the toxicity of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, WHO classification, and International Prognostic Index score. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; oral prednisone on days 1-5; and filgrastim (G-CSF) subcutaneously on days 1-14. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive cyclophosphamide, doxorubicin, vincristine, prednisone, and G-CSF as in arm I. Patients also receive rituximab IV on day 3 of courses 1-2 and on day 1 of courses 3-6 for a total of 6 doses. Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 400 patients (200 per treatment arm) will be accrued for this study within 5 years.

Official Title
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A Randomized Phase III Study Of Chimeric Anti-CD20 Monoclonal Antibody (Rituximab) With 2-Weekly CHOP Chemotherapy In Elderly Patients With Intermediate Or High-Risk Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Biological: rituximab
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: prednisone
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed non-Hodgkin's lymphoma (NHL) Low- or high-intermediate or high-risk lymphoma of any of the following subtypes: Mantle cell lymphoma Follicular lymphoma (grade III) Diffuse large B-cell lymphoma CD20-positive No suspected or documented CNS involvement by NHL 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: 65 and over Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 1.75 mg/dL* Transaminases less than 2.5 times normal* NOTE: * Unless due to NHL Renal: Creatinine less than 1.7 mg/dL (unless due to NHL) Cardiovascular: No severe cardiac dysfunction No New York Heart Association class II-IV heart disease LVEF at least 45% Pulmonary: No uncontrolled asthma requiring steroid treatment Other: HIV negative No intolerance to exogenous protein administration No active, uncontrolled infection No uncontrolled allergy requiring steroid treatment No other malignancy within the past 5 years except basal cell skin cancer or stage 0 cervical cancer PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy for NHL Chemotherapy: No prior chemotherapy for NHL Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy for NHL except local radiotherapy for potential organ dysfunction by localized lymphoma mass or infiltration Concurrent local radiotherapy for potential or actual organ dysfunction by localized lymphoma mass or infiltration allowed Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 65 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Biological: rituximab|nan|
|Drug: cyclophosphamide|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: prednisone|nan|
|Drug: vincristine sulfate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response |  |  | 
| Overall survival |  |  | 
| Disease-free interval |  |  | 
| Toxicity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I grade 3 follicular lymphoma, stage I adult diffuse large cell lymphoma, stage III grade 3 follicular lymphoma, stage III adult diffuse large cell lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse large cell lymphoma, stage I mantle cell lymphoma, contiguous stage II grade 3 follicular lymphoma, contiguous stage II mantle cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma