Objectives
Primary Objective:
To determine the 18-month progression-free survival (PFS) in patients with previously untreated mantle cell lymphoma who are treated with aggressive chemo-immunotherapy and autologous stem cell transplant followed by randomization to either maintenance or consolidation bortezomib therapy
Secondary Objectives:
* To determine the toxicity profiles of maintenance and consolidation bortezomib by evaluating the number of patients able to complete all maintenance or consolidation therapy
* To determine the complete response rate to intensive chemo-immunotherapy plus maintenance or consolidation bortezomib
* To determine time to progression and overall survival using these two treatment regimens
Correlative/Other Pre-Specified Objectives:
* To determine the importance of p53 mutation or deletion on patient outcome with respect to CR rate, PFS, and OS
* To determine the importance of Ki67, cyclin D1, phosphohistone 3, p27, p21, p16, and PARP p85 expression in pre-treatment tumor biopsies with respect to CR rate, PFS, and OS
* To determine the relationship between proliferation signature and clinical outcome using quantitative real-time RT-PCR
* To evaluate the importance of quantitative cyclin D1 expression and expression of cyclin D1 isoforms in predicting clinical outcome using quantitative real-time RT-PCR
* To evaluate the prognostic significance of microRNAs in mantle cell lymphoma using microRNA arras
* To explore the correlation of selected microRNA polymorphisms with gene target expression with clinical outcomes such as response, PFS, and OS
* To determine changes in gene expression profile from diagnosis to relapse samples to identify genes differentially silenced or over-expressed with disease recurrence
* To determine the importance of early PCR negativity (following Treatment 2) using bcl-1/IgH junction and/or IgH chain gene rearrangement with respect to maintained PFS and the success of maintenance or consolidation therapy to converting patients to PCR negative status
OUTLINE OF INTERVENTIONS:
CHEMOIMMUNOTHERAPY: Patients receive chemoimmunotherapy comprising rituximab\* intravenously (IV) over 4-6 hours on day 1, methotrexate (MTX) IV over 4 hours on day 2, cyclophosphamide IV over 2 hours, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3, and prednisone orally (PO) on days 3-7. Beginning 24 hours after completion of MTX, patients receive leucovorin calcium IV every 6 hours until blood levels of MTX are in a safe range. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily (QD) beginning on day 3 and continuing until blood counts recover. Beginning no sooner than day 22, but no later that day 29 of the first course, patients receive a second course of chemoimmunotherapy as above. Patients with \> 15% persistent bone marrow involvement may receive a third course of chemoimmunotherapy. Patients are restaged and those with progressive disease are removed from therapy.
NOTE: \*During the first course of chemoimmunotherapy, patients receive rituximab only if the number of circulating mantle cells is =\< 10,000/mm\^3, otherwise, rituximab is omitted during the first course of chemoimmunotherapy.
HIGH-DOSE CONSOLIDATION CHEMOIMMUNOTHERAPY AND PERIPHERAL BLOOD STEM CELL (PBSC) COLLECTION: Approximately 4 weeks after completion of chemoimmunotherapy, patients receive high-dose consolidation chemoimmunotherapy comprising cytarabine IV over 2 hours and etoposide phosphate IV continuously on days 1-4, and rituximab IV over 4-6 hours on days 5 and 12 OR 6 and 13. Beginning on day 14 and continuing until completion of PBSC collection, patients receive G-CSF SC QD. Once blood counts recover, patients undergo 1-3 leukapheresis procedures for collection of PBSCs on days 22-25.
HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS PBSC TRANSPLANTATION (PBSCT): Beginning 4-6 weeks after completion of leukapheresis, patients receive carmustine IV over 2 hours on day -6, etoposide phosphate IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2. Patients undergo autologous PBSCT on day 0. Patients also receive G-CSF SC QD beginning on day 4 and continuing until blood counts recover.
POST-TRANSPLANTATION IMMUNOTHERAPY: Approximately 5 weeks after autologous PBSCT, patients receive rituximab IV over 4-6 hours once weekly for 2 weeks. Approximately 4 weeks after completion of post-transplantation immunotherapy, patients proceed to maintenance therapy or consolidation therapy with bortezomib as described in the Arms section.
After completion of study treatment, patients are followed every 2 months for 2 years, every 6 months for 3 years, and then annually for 5 years.
