Combination Chemotherapy With or Without Rituximab in Non-Hodgkin's Lymphoma

OBJECTIVES: * Compare the time to treatment failure in patients with CD20-positive diffuse large B-cell non-Hodgkin's lymphoma treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like chemotherapy with vs without rituximab. * Compare the tumor control, progression rate, and complete remission rate in patients treated with these regimens. * Compare the disease-free and overall survival rate of patients treated with these regimens. * Compare the toxicity of these regimens in these patients. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center, bulky disease (no vs yes), International Prognostic Index score (0 vs 1), and chemotherapy (CHOP vs CHOEP vs PMitCEBO vs MACOP-B). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive 1 of the following chemotherapy regimens according to participating country: * CHOP: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone or prednisolone on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. * CHOEP-21: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; etoposide IV on days 1-3; and oral prednisone on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. * PMitCEBO: Patients receive mitoxantrone IV, cyclophosphamide IV, and etoposide IV on day 1; vincristine IV and bleomycin IV on day 8; and oral prednisolone daily during weeks 1-4 and every other day during week 5. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. * MACOP-B: Patients receive cyclophosphamide IV and doxorubicin IV on days 1, 15, 29, 43, 57, and 71; methotrexate IV and vincristine IV on days 8, 36, and 64; bleomycin IV and vincristine IV on days 22, 50, and 78; and oral or intramuscular prednisone on days 1-84. Treatment continues in the absence of disease progression or unacceptable toxicity. * Arm II: Patients receive arm I regimens (according to participating country) and rituximab as follows: * CHOP and rituximab: Patients receive CHOP as in arm I and rituximab IV on day 1. * CHOEP-21 and rituximab: Patients receive CHOEP-21 as in arm I and rituximab IV on day 1. * PMitCEBO and rituximab: Patients receive PMitCEBO as in arm I and rituximab IV on day 1 during courses 1 and 4; on day 8 during courses 2 and 5; and on day 1 at 1 and 4 weeks after completion of the last course of PMitCEBO chemotherapy. * MACOP-B and rituximab: Patients receive MACOP-B as in arm I and rituximab IV on days 1, 22, 43, 64, 85, and 106. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 820 patients will be accrued for this study within approximately 2 years.