S1106 Rituximab With Combination Chemotherapy or Bendamustine Hydrochloride Followed by Consolidation Chemotherapy and Stem Cell Transplantation in Older Patients With Previously Untreated Mantle Cell Lymphoma

OBJECTIVES: * To estimate the 2-year progression-free survival (PFS) of patients with newly diagnosed mantle cell lymphoma (MCL) treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, dexamethasone (RHCVAD), methotrexate and cytarabine (MTX/Ara-C), and autologous stem cell transplant (ASCT) or rituximab and bendamustine (R-bendamustine) and autologous stem cell transplant and to select a regimen for further development. * To assess the response rate and overall survival of patients with newly diagnosed MCL treated with R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine and ASCT. * To assess the toxicity and tolerability of R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine and ASCT in patients with newly diagnosed MCL. * To determine the prognostic value of quantitative minimal-residual disease (MRD) monitoring in the peripheral blood of MCL patients after induction therapy and serially after high-dose chemotherapy and ASCT on treatment outcome. * To bank diagnostic tissue sections for future translational research studies. OUTLINE: This is a multicenter study. Patients are stratified according to risk classification by Mantle Cell Lymphoma International prognostic Index (MIPI) score (low risk vs intermediate/high risk). Patients are randomized to 1 of 2 treatment arms. * Arm I (induction therapy): * Courses 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. * Course 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of course 2. * Each course is 21 days long and continues in the absence of disease progression or unacceptable toxicity. * Arm II (induction therapy): * Course 1-6: Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks later, patients with responsive disease receive 2 additional courses of treatment. * Stem cell mobilization: Beginning within 8 weeks, patients receive rituximab IV and cyclophosphamide IV over 1 hour on day 1. Patients then undergo stem cell collection about 26 days later. Consolidation therapy: Patients receive one of the following preparative regimens. * BCV\* chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2. * BEAM\* chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1. * TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)\*\* twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2. * NOTE: \* Patients 61 years of age or older receive either BCV or BEAM. * NOTE: \* \*TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0. After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually for up to 8 years from registration.