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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00310037
First received: March 29, 2006
Last updated: June 22, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Mantle Cell Lymphoma
Drug: bortezomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Maintenance vs Consolidation Bortezomib Therapy Following Aggressive Chemo-Immunotherapy and Autologous Stem Cell Transplant for Previously Untreated Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Complete response rate to intensive chemo-immunotherapy plus maintenance or consolidation bortezomib [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
  • Incidence of toxicity, graded according to Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 151
Study Start Date: June 2006
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A maintenance therapy
Patients receive bortezomib 1.6 mg/m^2 IV on days 1, 8, 15, and 22 once daily for 4 weeks. There will be a 4 week rest period. One cycle is a total of 8 weeks. A total of 10 cycles of bortezomib will be given in the absence of disease progression or unacceptable toxicity.
Drug: bortezomib
Given IV
Experimental: Arm B consolidation therapy
Patients received to Arm B receive bortezomib 1.3 mg/m^2 IV on days 1, 4, 8, and 11 once daily for 3 weeks. One cycle is a total of 3 weeks. A total of 4 cycles of bortezomib will be given in the absence of disease progression or unacceptable toxicity.
Drug: bortezomib
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00310037

  Show 48 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Millennium Pharmaceuticals, Inc.
Investigators
Study Chair: Lawrence D. Kaplan, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00310037     History of Changes
Other Study ID Numbers: CALGB-50403, CDR0000466167
Study First Received: March 29, 2006
Last Updated: June 22, 2015
Health Authority: United States: NCI Central Institutional Review Board

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bortezomib
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 01, 2015