RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which schedule of rituximab and combination chemotherapy is more effective in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and combination chemotherapy to compare how well they work in treating patients with aggressive B-cell non-Hodgkin's lymphoma.

OBJECTIVES:

Primary

• Compare the efficacy of 2 different schedules of immunochemotherapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in patients with previously untreated, low-risk, aggressive B-cell non-Hodgkin's lymphoma.
• Compare acute and chronic side effects in patients treated with these regimens.
• Compare time to treatment failure in patients treated with these regimens.

Secondary

• Compare the time to progression in patients treated with these regimens.
• Compare the overall and disease-free/relapse-free survival of patients treated with these regimens.
• Compare the complete response rate in patients treated with these regimens.
• Compare the tumor control in patients treated with these regimens.
• Compare the safety of these regimens in these patients.
• Compare the pharmacoeconomics of these regimens.
• Compare patient adherence to these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

All patients are given the option of receiving a 1-week course of pretreatment therapy comprising vincristine IV once on day -6 and oral prednisone once daily on days -6 to 0.

• Arm I: Patients receive R-CHOP immunochemotherapy comprising rituximab IV, cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 3 more courses of R-CHOP.
• Arm II: Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo restaging of their disease. Patients with disease progression proceed to salvage therapy off study. All other patients receive 1 more course of R-CHOP followed by 2 courses of rituximab alone.

All patients undergo final restaging after 6 courses of rituximab. Patients with disease progression, stable disease, or partial response proceed to salvage therapy off study.

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 622 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma, including the following subtypes:

  • Grade 3 follicular lymphoma

  • Diffuse B-cell lymphoma, including diffuse large cell lymphoma with any of the following variants:

    • Centroblastic
    • Immunoblastic
    • Plasmablastic
    • Anaplastic large cell
    • T-cell-rich B-cell lymphoma

  • Primary effusion lymphoma

  • Intravascular B-cell lymphoma

  • Primary mediastinal B-cell lymphoma

  • Burkitt's or Burkitt-like lymphoma

  • Mantle cell lymphoma (blastoid)

  • Aggressive marginal zone lymphoma (monocytoid)

• Previously untreated disease

• CD20-positive disease

• International Prognostic Index (IPI) score 0

• No bulky disease

  • Largest single or conglomerate tumor < 7.5 cm in diameter

• No mucosa-associated lymphoid tissue (MALT) lymphoma

• No CNS involvement of lymphoma (intracerebral, meningeal, or intraspinal)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 2,500/mm^3
• Lactate dehydrogenase normal
• Not pregnant or lactating
• Fertile patients must use effective contraception during and for 1 year after study participation
• Negative pregnancy test
• No known hypersensitivity to the study medications
• No known HIV-positivity
• No active hepatitis infection
• No impaired left ventricular function
• No severe cardiac arrhythmias
• No other impaired organ function
• No other serious disorder
• No other malignancy within the past 5 years except carcinoma in situ or basal cell skin cancer

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy
• No prior immunosuppressive treatment with cytostatics
• No planned radiotherapy to extranodal involvement
• No concurrent participation in other treatment studies