Bortezomib After Combination Chemotherapy, Rituximab, and an Autologous Stem Cell Transplant in Treating Patients With Mantle Cell Lymphoma
Condition: Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: bortezomib
Intervention description: Given IV
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 151.0
Sex: All
Minimum age: 18 Years
Maximum age: 69 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well bortezomib works when given after combination
      chemotherapy, rituximab, and an autologous stem cell transplant in treating patients with
      mantle cell lymphoma. Bortezomib may stop the growth of cancer cells by blocking some of the
      enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the
      growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving
      more than one drug (combination chemotherapy) together with an autologous stem cell
      transplant may allow more chemotherapy to be given so that more cancer cells are killed.
      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. Giving bortezomib after combination
      chemotherapy, monoclonal antibody therapy, and an autologous stem cell transplant may kill
      any remaining cancer cells or keep the cancer from coming back.
    

Eligibility criteria:

        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).