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

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