PRIMARY OBJECTIVES:~I. To determine the overall response rate (ORR), and in particular, the complete remission rate (CRR) in previously untreated MCL treated with ofatumumab in combination with aggressive chemo-immunotherapy.~SECONDARY OBJECTIVES:~I. To determine the high sensitivity flow cytometry (HSFCM) complete remission rate (HSFCM-CRR) in previously untreated MCL treated with ofatumumab in combination with aggressive chemo-immunotherapy +/- high dose chemotherapy and autologous stem cell transplant (HDC-ASCT).~II. To determine the time-to-progression (TTP), progression-free survival (PFS) and overall survival (OS) of patients with previously untreated MCL treated with ofatumumab and aggressive chemoimmunotherapy +/- HDC-ASCT.~III. To determine the toxicity profiles of ofatumumab in combination with high dose cytarabine chemoimmunotherapy +/- HDC-ASCT.~IV. To correlate minimal residual disease (MRD) at different time intervals with TTP, PFS, and OS.~V. To correlate surface cluster of differentiation (CD)20 levels, Ki67, and additional cytogenetic abnormalities in pretreatment tumor biopsies with respect to ORR, CRR, TTP, PFS, or OS.~VI. To determine the relationship between proliferation signature and clinical outcome using quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR).~VII. To determine changes in surface CD20 levels, Ki67, or gain of additional cytogenetic abnormalities in relapsed/refractory tumor specimens.~VIII. To correlate serum component (C)3, C4, and hemolytic complement (CH)50 levels measured at baseline and at the end of first ofatumumab infusion with ORR, CRR, median response rate (MRR), TTP, PFS and OS.~IX. Evaluate the ability of the induction and consolidation therapy to get 70% of patients to autologous stem cell transplantation.~X. Evaluate the tolerability and CD34+ cell yield following therapy with patient and hyper-fractionated cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and dexamethasone (HyperCVAD)/high-dose cytarabine and methotrexate (HD-MA).~XI. To compare differences in response rate in patients with MCL treated with ofatumumab + HyperCVAD/HD-MA according Cheson and Modified Cheson Criteria.~OUTLINE:~COURSES 1, 3, and 5 (O-HyperCVAD): Patients receive ofatumumab intravenously (IV) on day 1, cyclophosphamide IV over 2 hours every 12 hours for 6 doses on days 3-5, doxorubicin hydrochloride IV continuously over 72 hours on days 6-8, vincristine sulfate IV on days 6 and 13, and dexamethasone IV or orally (PO) on days 3-6 and 13-16.~COURSES 2, 4, and 6 (O-HD-MA): Patients receive ofatumumab IV on day 1, methotrexate IV continuously over 24 hours on day 3, and cytarabine IV over 2 hours every 12 hours on days 4-5.~Treatment repeats every 21 days for 6* courses in the absence of disease progression or unacceptable toxicity.~Eligible patients then undergo standard high dose chemotherapy and autologous stem cell transplant (HDC-ASCT). Patients achieving a high sensitivity flow cytometry complete remission (HSFCM-CR) after 2 courses may proceed to HDC-ASCT after completing 4 courses of treatment.~After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months for 3 years, and then as clinically instructed.
This phase II trial studies how well ofatumumab in combination with cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and dexamethasone alternating with ofatumumab in combination with cytarabine and methotrexate works in treating patients with newly diagnosed mantle cell lymphoma (MCL). Monoclonal antibodies, such as ofatumumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, dexamethasone, cytarabine, and methotrexate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ofatumumab together with alternating regimens of combination chemotherapy may kill more cancer cells.