Combination Therapy Using Lenalidomide (Revlimid)- Low Dose Dexamethasone and Rituximab for Treatment of Rituximab-Resistant, Non-Aggressive B-Cell Lymphomas
Condition: Follicular Lymphoma; Marginal Zone B-Cell Lymphoma; MALT Lymphoma; Lymphoma of Mucosa-Associated Lymphoid Tissue; Lymphoma, Small Lymphocytic; Waldenstrom Macroglobulinemia; Mantle-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Lenalidomide; Dexamethasone; Rituximab
Intervention description: Lenalidomide: 10mg capsules, orally, once daily for each 28 day cycle for the duration of the study; Dexamethasone: 8mg tablets, orally, once weekly on days 3, 10, 17, 24 of each 28 day cycle for the duration of the study;; Rituximab: 375mg/m2 IV (in the vein), once weekly on days 1, 8, 15, 22 during month 3 of therapy
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Rituximab; Lenalidomide; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Revlimid; Celgene brand of lenalidomide; lenalidomide; Rituxan; CD20 antibody, rituximab; rituximab; Follicular Lymphoma; Marginal Zone B-Cell Lymphoma; Lymphoma, Small Lymphocytic; Waldenstrom Macroglobulinemia; Mantle-Cell Lymphoma; Antigens, CD20; refractory; resistantRefractory/progressive lymphoma less than 6 months from first rituximab dose of previous rituximab-containing regimen; Previously treated; Treated with rituximab

Summary:

      Pre-clinical data and recently published clinical data suggest a synergistic effect between
      lenalidomide and dexamethasone. We hypothesize that a combination of
      lenalidomide-dexamethasone can overcome rituximab resistance. To determine the response rate
      to lenalidomide and dexamethasone plus rituximab therapy in subjects with recurrent small
      B-cell non-Hodgkin lymphoma who have had lymphoma progression within 6 months of being
      treated with rituximab alone or with a rituximab-containing regimen, we propose initial
      treatment with both drugs for two 28-day treatment cycles (Part I). After response assessment
      following two cycles of lenalidomide-dexamethasone, patients will enter Part II of the study.
      In Part II, patients will receive lenalidomide-dexamethasone and rituximab to evaluate the
      potential reversal of rituximab resistance as measured by response to rituximab and
      progression-free survival following rituximab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previously treated, histologically confirmed follicular lymphoma (grade 1, 2, 3a),
             marginal zone lymphoma, small lymphocytic lymphoma with less than <5000
             lymphocytes/mm3 or lymphoplasmacytic lymphoma with <3g/mL IgM, mantle cell lymphoma by
             WHO classification

          -  Flow cytometry or immunohistochemistry must document CD20 antigen expression. Past
             documentation of CD20 antigen expression is admissible.

          -  Subjects must have been treated with rituximab in combination with chemotherapy or as
             monotherapy and must have refractory or progressive disease <6 months from the first
             rituximab dose of previous rituximab containing regimen

          -  At least 18 years of age

          -  ECOG performance status 0-2

          -  Measurable disease must be present on physical examination or imaging studies. Any
             tumor mass >2cm is considered measurable.

          -  Lesions that are considered non-measurable, but assessable include the following: bone
             lesions, ascites, pleural/pericardial effusion, lymphangitis cutis/pulmonis, bone
             marrow

          -  Patients with a history of intravenous drug abuse or any behavior associated with
             increased risk of HIV infection should be tested for exposure to the HIV virus

          -  Understand and voluntarily sign an informed consent

          -  Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
             intolerant of ASA may use warfarin or low molecular weight heparin)

          -  Laboratory test results within these ranges: absolute neutrophil count greater than or
             equal to 1500/mm3; platelet count greater than or equal to 75,000/mm3; serum
             creatinine less than or equal to 2.0mg/dL; total bilirubin less than or equal to
             1.5mg/dL (unless due to Gilbert's syndrome); AST (SGOT) and ALT (SGPT) less than or
             equal to 2.5 x ULN or less than or equal to 5 x ULN if hepatic metastases are present

          -  Disease free of prior malignancies for greater than or equal to 5 years with the
             exception of currently treated basal cell or squamous cell carcinoma of the skin, or
             carcinoma "in situ" of the cervix or breast

          -  All study participants must be registered into the mandatory RevAssist program, and be
             willing and able to comply with the requirements of RevAssist

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again
             within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7
             days) and must either commit to continued abstinence from heterosexual intercourse or
             begin TWO acceptable methods of birth control, one highly effective method and one
             additional effective method AT THE SAME TIME, at least 28 days before she starts
             taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree
             to use a latex condom during sexual contact with a FCBP even if they have had a
             successful vasectomy.

        Exclusion Criteria:

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from following study procedure

          -  Pregnant or breast-feeding females

          -  Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study

          -  Use of any other experimental drug or therapy within 28 days of baseline

          -  Known hypersensitivity to thalidomide

          -  The development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide or similar drugs

          -  Any prior use of lenalidomide

          -  Known positivity for HIV or active infectious Hepatitis, type A, B, or C. Patients who
             test positive or who are known to be infected are not eligible due to an increased
             risk of infection with this regimen. HIV testing is not required for study entry, but
             is required if the patient is perceived to be at risk.

          -  Known central nervous system involvement by lymphoma