This phase II trial is studying how well giving rituximab together with combination chemotherapy and bortezomib works in treating patients with untreated mantle cell lymphoma. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving rituximab together with combination chemotherapy and bortezomib may kill more cancer cells.

Treatment consists of six agents: bortezomib (Vc), rituximab (R), cyclophosphamide (C), vincristine (V), doxorubicin (A), and dexamethasone (D) (VcR-CVAD).

PRIMARY OBJECTIVES:

I. To evaluate the complete response (CR) rate in patients with mantle cell lymphoma, who are treated with VcR-CVAD.

SECONDARY OBJECTIVES:

I. To evaluate the overall response rate to VcR-CVAD. II. To evaluate the progression-free survival (PFS) and overall survival (OS) of patients receiving maintenance rituximab after VcR-CVAD induction.

III. To evaluate the PFS and OS of patients who receive autologous stem cell transplantation (ASCT) after VcR-CVAD induction.

IV. To evaluate the toxicity of VcR-CVAD.

TERTIARY OBJECTIVES:

I. Evaluation of antigen expression patterns to determine or confirm possible unique expressions of MCL.

II. To evaluate the percentage of circulating mantle cell lymphoma (MCL) cells.

OUTLINE: This is a multicenter study.

Induction therapy (VcR-CVAD): Patients receive VcR-CVAD comprising bortezomib 1.3 mg/m2 IV over 3-5 seconds on days 1 and 4; rituximab 375 mg/m2 IV over 3-4 hours on day 1; doxorubicin hydrochloride 25 mg/m2/d IV over 48 hours on days 1 and 2; cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours on days 1-3; vincristine 1 mg IV over 3-5 seconds on day 3; and dexamethasone 40 mg IV or orally once daily on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) or IV once daily beginning on day 5 or 6 and continuing until blood counts recover OR pegfilgrastim SC on day 5 or 6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Maintenance therapy: Beginning 4-8 weeks after completion of induction therapy, patients receive rituximab IV over 3-4 hours once weekly for 4 weeks. Treatment repeats every 6 months for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of induction therapy, patients who are eligible may have the option to receive consolidation therapy for autologous stem cell transplantation (ASCT) (off-study). These patients undergo stem cell harvest during courses 4, 5, or 6 of induction therapy.

After completion of study treatment, patients are followed periodically for up to 10 years.

Inclusion Criteria:

• Patients must have a histologically confirmed diagnosis of mantle cell lymphoma by demonstrating appropriate morphology plus at least one of the following on the biopsy specimen: nuclear cyclin D1+ by immunohistochemistry; t(11;14) by fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), or conventional karyotyping
• No prior chemotherapy, immunotherapy or radiotherapy for mantle cell lymphoma; a brief course of steroids (< 14 days) for symptom relief or steroids for other indications are allowed
• Patients must have measurable disease; CT scans at baseline are required to define the extent of measurable disease; the scans must be obtained within 6 weeks prior to registration; combined CT/PET scans may be used for the baseline and subsequent evaluations if accurate tumor measurements can be obtained from the CT component
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) > 1500 mm^3 (unless low count due to marrow involvement or splenomegaly)
• Platelets > 100,000 mm^3 (unless low counts due to marrow involvement or splenomegaly)
• Creatinine < 2 mg/dL
• Bilirubin < 2 mg/dL (may be up to 3.0 mg/dL if due to Gilbert's disease or due to liver involvement by lymphoma)
• Patients over the age of 45 must have a left ventricular ejection fraction (LVEF) of greater than 45% documented within 90 days prior to registration
• Patients must be tested for Hepatitis B surface antigen (HBs Ag) within 4 weeks prior to registration NOTE: HBs Ag positive patients are not excluded but will have more stringent monitoring of liver function tests

Exclusion Criteria:

• Known HIV disease; an HIV test is not required for entry on study but is required if the patient is perceived to be at risk; patients with a history of intravenous drug use or any other behavior with an increased risk for HIV infection should be tested for exposure to the HIV virus; patients with known HIV are excluded since the immunocompromised state of patients with HIV infection or the concomitant use of highly active antiretroviral therapy (HAART) may result in more extensive dose modifications than intended for the intensive therapeutic regimen used in this study

• Pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; women of childbearing potential and sexually active males must use an accepted and effective method of contraception

• Grade 2 or higher baseline peripheral neuropathy

• Known hypersensitivity to boron or mannitol

• History of prior malignancy unless at least one of the following conditions are met:

  • Malignancy was in-situ
  • Malignancy was treated surgically or with local radiation therapy with curative intent and the patient has been disease free for > 3 years
  • Any adjuvant hormonal therapy must have been discontinued > 3 months prior to registration

• Known central nervous system (CNS) involvement