Rituximab, Bendamustine Hydrochloride, and Bortezomib Followed by Rituximab and Lenalidomide in Treating Older Patients With Previously Untreated Mantle Cell Lymphoma

  • Study type:

    Interventional What is this?

    Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Study phase:

    II What is this?

    During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

Study IDs

  • Site IRB:

    • Rochester, Minnesota: 12-005758
  • NCT ID:

    NCT01415752
  • Sponsor Protocol Number:

    E1411

About this study

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma.

PURPOSE: This randomized phase II trial studies rituximab, bortezomib, bendamustine, and lenalidomide in treating previously untreated older patients with mantle cell lymphoma.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Disease Characteristics:

  • Histologically confirmed untreated mantle cell lymphoma (MCL), with documented cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH)
  • Patients must have at least one objective measurable disease parameter
    • Abnormal PET scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging
    • Measurable disease in the liver is required if the liver is the only site of lymphoma
  • Patient must have no CNS involvement

Patient Characteristics:

  • ECOG performance status 0-2
  • ANC ≥ 1,500/mcL (1.5 x 10^9/L)*
  • Platelets ≥ 100,000/mcL (100 x 10^9/L)* NOTE: *Unless due to marrow involvement.
  • AST/ALT ≤ 2 times upper limit of normal (ULN)
  • Bilirubin ≤ 2 times ULN
  • Calculated creatinine clearance by Cockroft-Gault formula ≥ 30 mL/min
  • Women (sexually mature female) must not be pregnant or breast-feeding
  • Negative pregnancy test
  • Women of childbearing potential and sexually active males use an accepted and effective method of contraception
    • Men must agree to use a latex condom during sexual contact with a female of child-bearing potential, even if they have had a successful vasectomy
    • All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma, or any surgically or radiation-cured malignancy continuously disease free for ≥ 5 years so as not to interfere with interpretation of radiographic response
  • Patient agrees that if randomized to Arms C or D, and proceed onto Arms G or H, they must register into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®
    • Patients must have no medical contra-indications to, and be willing to take, deep vein thrombosis (DVT) prophylaxis as all patients registering to the lenalidomide/rituximab Arms G and H will be required to have DVT prophylaxis
      • Patients randomized to Arms G or H who have a history of a thrombotic vascular event will be required to have therapeutic doses of low-molecular weight heparin or warfarin to maintain an INR between 2.0 - 3.0
      • Patients on Arms G and H without a history of a thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis
        • Patients who are unable to tolerate aspirin should receive low molecular weight heparin therapy or warfarin treatment
    • Women must agree to abstain from donating blood during study participation and for at least 28 days after discontinuation from protocol treatment
    • Males must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from protocol treatment
  • HIV-positive patients are not excluded but, to enroll, must meet all of the below criteria:
    • HIV is sensitive to antiretroviral therapy
    • Must be willing to take effective antiretroviral therapy, if indicated
    • No history of CD4 prior to or at the time of lymphoma diagnosis < 300 cells/mm³
    • No history of AIDS-defining conditions
    • If on antiretroviral therapy, must not be taking zidovudine or stavudine
    • Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia (PCP) during therapy and until at least 2 months following the completion of therapy or until the CD4 cells recover to over 250 cells/mm³, whichever occurs later
  • Patients must not have grade 2 or greater peripheral neuropathy
  • Patients must not have NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
  • Patients must not have hypersensitivity to bortezomib, boron, or mannitol
  • Patients must not have a serious medical or psychiatric illness likely to interfere with study participation

Prior Concurrent Therapy:

  • No prior therapy for MCL, except < 1 week of steroid therapy for symptom control
  • HIV-positive patients are not excluded, but to enroll, must meet all of the below criteria:
    • Must be willing to take effective antiretroviral therapy if indicated
    • If on antiretroviral therapy, must not be taking zidovudine or stavudine
  • Patients must not be participating in any other clinical trial or taking any other experimental medications within 14 days prior to registration

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

David Inwards, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015