Rituximab and Combination Chemotherapy in Treating Older Patients With Previously Untreated B-Cell Lymphoma

OBJECTIVES: Primary * Determine a pharmacokinetic profile for pharmacokinetics-based or rituximab within a CHOP-14 regimen comprising cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in elderly patients with previously untreated aggressive B-cell lymphoma. * To determine whether increased single-doses of rituximab for males can compensate their lower serum levels. * Evaluate the safety and toxicity profile of this regimen in male patients. Secondary * Determine the rate of complete responses, primary progressions under therapy, event-free survival, progression-free survival, and overall survival in patients treated with this regimen. * Determine the rate of primary progression in patients treated with this regimen. OUTLINE: This is a multicenter study. All patients undergo the following treatment. * Prephase treatment: Patients receive vincristine subcutaneously on day -6 and oral prednisone on days -6 to 0. * Immunochemotherapy and radiotherapy: Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Patients also receive pegfilgrastim subcutaneously on days 4, 18, 32, 46, 60, and 74. Treatment with CHOP chemotherapy repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who show no response after course 4 of CHOP chemotherapy proceed to salvage chemotherapy off study. Patients are evaluated 2-4 weeks after completion of CHOP. Patients with initial bulky disease (i.e., diameter ≥ 7.5 cm) or extranodal involvement AND achieving complete remission (CR), unconfirmed CR (CRu), or partial remission undergo radiotherapy 5 days a week for 4 weeks. Patients who do not achieve CR or CRu 2 months after completion of radiotherapy proceed to salvage chemotherapy off study. Patients are then stratified according to center, International Prognostic Index (1-2 vs 3-5), disease involvement (bulky vs extranodal vs bulky and/or extranodal), age (61-70 years old vs 71-80 years old), and gender. Patients are randomized to 1 of 2 treatment arms. * Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. * Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Some patients undergo blood sample collection periodically during and after treatment for pharmacokinetic studies. After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year therafter.