Bortezomib After Combination Chemotherapy, Rituximab, and an Autologous Stem Cell Transplant in Treating Patients With Mantle Cell Lymphoma

1. Documentation of Disease

   A. Histologic Documentation:
   * Histologically documented mantle cell lymphoma with co-expression of CD20 (or CD19) and CD5 and lack of CD23 expression by immunophenotyping AND at least one of the following confirmatory tests:

     * positive immunostaining for cyclin D1; OR
     * the presence of t(11;14) on cytogenetic analysis; OR
     * molecular evidence of bcl-1/IgH rearrangement.
   * Cases that are CD5-negative and/or CD23-positive will be eligible provided that the histopathology is consistent with mantle cell lymphoma AND positive for cyclin D1, t(11;14), or bcl-1/IgH rearrangement.A tissue block should be submitted to the CALGB Pathology Coordinating Office for central pathology review.
   * A diagnosis based on peripheral blood or bone marrow is allowed. If the diagnosis is based only on blood, in addition to the immunophenotype and molecular confirmation above, a peripheral blood smear must be available for central pathology review. If the diagnosis is based on a bone marrow biopsy, the tissue block should be submitted.
   * Note: Failure to submit pathology materials within 60 days of patient registration will be considered a major protocol violation.

   B. Extent of Disease:
   * Stage I-IV. Patients with nodular histology mantle cell lymphoma must have Ann Arbor stage III or IV disease to be eligible. Patients with mantle zone histology will not be eligible because of their relatively favorable prognosis. Patients with other mantle cell histologies are eligible regardless of stage.
   * No active CNS disease defined as symptomatic meningeal lymphoma or known CNS parenchymal lymphoma. A lumbar puncture demonstrating mantle cell lymphoma at the time of registration to this study is not an exclusion for study enrollment.
2. Prior Treatment:

   A. Patients must be previously untreated or have received no more than one prior cycle of chemotherapy and/or rituximab treatment.

   B. No prior radiation therapy for mantle cell lymphoma.

   C. ≥ 2 weeks since major surgery.

   D. ≥ 3 weeks since prior chemotherapy.
3. Age Eligibility: Age ≥ 18 years and \< 70 years
4. Murine Products Hypersensitivity Eligibility: No known hypersensitivity to murine products.
5. Use of Systemic Corticosteroids Eligibility: No medical condition requiring chronic use of systemic corticosteroids.
6. Eligibility Criteria on HIV Infection: No HIV infection. Patients with a history of intravenous drug abuse or any behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. Patients who test positive or who are known to be infected are not eligible due to an increased risk of infection with this regimen. An HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk.
7. Non-pregnant and non-nursing: Non-pregnant and non-nursing. Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control.
8. HepBSAg or HepC Ab Eligibility: Patients who test positive for HepBSAg or HepC Ab are eligible provided all of the following criteria are met:

   A. bilirubin ≤ 2 x upper limit of normal; AND

   B. AST ≤ 3 x upper limit of normal; AND

   C. liver biopsy demonstrates ≤ grade 2 fibrosis and no cirrhosis.

   Hepatitis B surface Ag(+) patients will be treated with lamivudine (3TC) throughout protocol therapy and for 6-12 months thereafter.
9. Secondary Malignancy Eligibility: Patients with a "currently active" second malignancy, other than non-melanoma skin cancers are not eligible. This includes Waldenstrom's Macroglobulinemia, since such patents have experienced transient increases in IgM following initiation of rituximab, with the potential for hyperviscosity syndrome requiring plasmapheresis. Patients are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy, and are considered by their physician to be at less than 30% risk of relapse.
10. Initial Required Laboratory Values:

    * LVEF by MUGA or ECHO ≥ 45%
    * Creatinine ≤ 2.0 mg/dL
    * Total Bilirubin ≤ 2.0 mg/dL (Unless attributable to Gilbert's Disease)
    * u-HCG or serum HCG Negative (If patient of childbearing potential).