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

Not Recruiting

Trial ID: NCT01415752


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.

Official Title

Intergroup Randomized Phase 2 Four Arm Study In Patients ≥ 60 With Previously Untreated Mantle Cell Lymphoma Of Therapy With: Arm A = Rituximab+ Bendamustine Followed By Rituximab Consolidation (RB → R); Arm B = Rituximab + Bendamustine + Bortezomib Followed By Rituximab Consolidation (RBV→ R), Arm C = Rituximab + Bendamustine Followed By Lenalidomide + Rituximab Consolidation (RB → LR) or Arm D = Rituximab + Bendamustine + Bortezomib Followed By Lenalidomide + Rituximab Consolidation (RBV → LR)

Stanford Investigator(s)

Ranjana Advani
Ranjana Advani

Saul A. Rosenberg, MD, Professor of Lymphoma

Richard Hoppe
Richard Hoppe

Henry S. Kaplan-Harry Lebeson Professor of Cancer Biology



   - 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

   - Patient must have no CNS involvement


   - 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

   - 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

   - HIV-positive patients are not excluded but, to enroll, must meet all of the below

      - 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

   - 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


   - 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

      - 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


drug: bendamustine hydrochloride

drug: bortezomib

drug: lenalidomide

biological: rituximab

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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