Bortezomib, Rituximab and Combination Chemotherapy in Treating Participants With Mantle Cell Lymphoma

PRIMARY OBJECTIVES: I. Determine the safety and the maximum tolerated dose (MTD) of bortezomib when added to the combination of rituximab, methotrexate, and cytarabine alternating with bortezomib, rituximab-hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone (hyperCVAD) in patients with untreated aggressive mantle cell lymphoma. (Phase I) II. Evaluate the time to failure (TTF) rate following therapy with bortezomib plus rituximab-hyperCVAD alternating with bortezomib plus rituximab-high dose methotrexate/cytarabine in patients between 18 and 79 years of age with untreated aggressive mantle cell lymphoma. (Phase II) SECONDARY OBJECTIVES: I. Evaluate overall response rate, complete remission rate, overall survival, and duration of remission. (Phase I) II. Evaluate overall response rate, overall survival, and duration of remission. (Phase II) III. Evaluate toxicity of the combination regimen. (Phase II) IV. Correlate outcome with pretreatment markers. (Phase II) OUTLINE: This is a phase I, dose-escalation study of bortezomib followed by a phase II study. Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease progression or unacceptable toxicity. Drug Combination I: Participants receive rituximab intravenously (IV) over 6 hours on day 1, cyclophosphamide IV over 3 hours twice daily (BID) on days 2-4, doxorubicin IV over 15-30 minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone orally (PO) or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day 5. Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4. After completion of study treatment, participants are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.