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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00310037
Recruitment Status : Active, not recruiting
First Posted : April 3, 2006
Results First Posted : July 31, 2018
Last Update Posted : August 18, 2021
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Mantle Cell Lymphoma Drug: bortezomib Phase 2

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 151 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : June 2006
Actual Primary Completion Date : December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Bortezomib

Arms and Interventions
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Arm Intervention/treatment
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 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


Outcome Measures
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Primary Outcome Measures :
  1. Progression-free Survival Rate at 18 Months [ Time Frame: At 18 months ]
    Progression free survival (PFS) rate at 18 months was defined as the proportion of patients that were alive and progression-free 18 months after registration into the study. The Kaplan-Meier method of 18 month progression-free survival was calculated..


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: Up to 10 years ]
    Overall Survival (OS) was measured from the date of study entry to date of death due to any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.

  2. Number of Participants With Complete Response Intensive Chemo-immunotherapy Plus Maintenance or Consolidation Bortezomib [ Time Frame: Up to 10 years ]

    Complete response is:

    • Complete disappearance of all detectable clinical and radiographic evidence of target lesions and disappearance of all disease-related symptoms if present prior to therapy and normalization of biochemical abnormalities definitely assignable to NHL
    • All lymph nodes and nodal masses must have regressed to normal size (<= 1.5 cm in the greatest transverse diameter (GTD) for nodes > 1.5 cm prior to therapy) or <= 1 cm for nodes that were 1.1-1.5 cm in the GTD prior to therapy or by more than 75% in the sum of the products of the GTD
    • The spleen, if enlarged before therapy, must have regressed in size and must not be palpable on physical examination. Any macroscopic nodules in any organs detectable on imaging studies should no longer be present. Other organs enlarged prior to therapy due to involvement of lymphoma must have decreased in size
    • If bone marrow was involved by lymphoma prior to treatment, infiltrate must be cleared on repeat bone marrow aspirate

  3. Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment. [ Time Frame: Duration of treatment (up to approximately 2 years) ]
    The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.


Eligibility Criteria
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Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00310037


Locations
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Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Millennium Pharmaceuticals, Inc.
Investigators
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Study Chair: Lawrence D. Kaplan, MD University of California, San Francisco
More Information
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Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00310037    
Other Study ID Numbers: CALGB-50403
CDR0000466167 ( Other Identifier: NCI Physician Data Query )
First Posted: April 3, 2006    Key Record Dates
Results First Posted: July 31, 2018
Last Update Posted: August 18, 2021
Last Verified: August 2021
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Bortezomib
Antineoplastic Agents