Combination Chemotherapy With or Without Rituximab in Treating Patients With Newly Diagnosed 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 cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy plus rituximab is more effective than combination chemotherapy alone for non-Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without rituximab in treating patients who have newly diagnosed non-Hodgkin's lymphoma that has not been treated previously.

Detailed Description
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OBJECTIVES: I. Determine whether the addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) increases the failure-free survival of patients with newly diagnosed, previously untreated, aggressive B-cell non-Hodgkin's lymphoma. II. Determine whether the addition of rituximab changes the toxicity profile attributed to CHOP chemotherapy in this patient population. OUTLINE: This is a randomized, multicenter study. Patients are stratified by center, histology (diffuse small cleaved cell, diffuse mixed, and diffuse large cell vs immunoblastic large cell, mantle cell, and marginal zone), and risk group (low vs intermediate vs high). Patients enter one of two treatment arms: Arm I: Patients receive rituximab IV on day 1, followed by cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisone for 5 consecutive days beginning on day 3. Arm II: Patients receive cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisone daily for 5 consecutive days beginning on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients will be followed for 3 years. PROJECTED ACCRUAL: A total of 270 patients (135 per treatment arm) will be accrued for this study within 3 years.

Official Title
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A Phase III Randomized Trial of CHOP Chemotherapy Plus Rituxan (IDEC-C2B8) Versus CHOP Chemotherapy Alone for Newly Diagnosed, Previously Untreated, Aggressive Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, newly diagnosed, aggressive (stage II-IV) B-cell non-Hodgkin's lymphoma, including but not limited to: Mantle cell Diffuse large cell Diffuse mixed cell Anaplastic large cell (B-cell type) Diffuse small cleaved cell Marginal zone lymphoma CD20 positive 19 years old and over WHO 0-2 Karnofsky 70-100% Life expectancy at least 6 months Absolute neutrophil count greater than 1,000/mm3 (unless due to non-Hodgkin's lymphoma (NHL) bone marrow involvement) Bilirubin less than 3.0 mg/dL Alkaline phosphatase less than 3 times upper limit of normal (ULN) SGOT less than 3 times ULN Fertile patients must use effective contraception HIV negative Nonsteroidal hormones for non-lymphoma related conditions allowed (e.g., insulin for diabetes) Exclusion Criteria: No prior T-cell lymphoma Not pregnant or nursing No other serious disease or medical condition that would interfere with compliance No other concurrent chemotherapy No concurrent corticosteroids (unless for prevention of nausea or vomiting) No concurrent radiotherapy No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 120 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: rituximab|nan|
|Drug: CHOP regimen|Cyclophosphamide, vincristine and doxorubicin as a drip into the bloodstream (intravenously) and prednisolone (steroid) as tablets taken with or after food.|
|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 |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II adult diffuse small cleaved cell lymphoma, stage II adult diffuse mixed cell lymphoma, stage II adult diffuse large cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, anaplastic large cell lymphoma, stage II mantle cell lymphoma, stage II small lymphocytic lymphoma, stage II marginal zone 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