Bendamustine and Rituximab Induction Therapy and Maintenance Rituximab and Lenalidomide in Previously Untreated CLL/SLL
Condition: Lymphoid Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid
Intervention: Bendamustine; Rituximab; Lenalidomide
Intervention description: Given IV; Given IV; Given PO
Intervention MeSH terms: Rituximab; Lenalidomide; Bendamustine Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lymphoid Leukemia; Bendamustine; Rituximab; Small Lymphocytic Lymphoma

Summary:

      The investigators propose a treatment strategy where patients are treated with induction
      chemoimmunotherapy consisting of rituximab + bendamustine for 6 cycles, followed by
      initiation of maintenance rituximab and lenalidomide among patients achieving an objective
      response (i.e., at least stable disease with some tumor shrinkage) to induction therapy. The
      goal of maintenance therapy will be to capitalize on the cytoreduction following induction
      chemotherapy with a maintenance regimen that has also shown promising activity in CLL, in
      order to allow for improved PFS in this population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma
             (SLL)

          -  No prior cytotoxic chemotherapy for their disease; prior therapy with single-agent
             rituximab is permitted

          -  Understand and voluntarily sign an informed consent document

          -  In cases of SLL, subjects must have at least one bidimensionally measurable lesion at
             least >= 1.5 cm measured in one dimension

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry

          -  Absolute neutrophil count >= 1500/uL

          -  Platelet count >= 100,000/uL

          -  Subjects with neutrophils < 1500/uL or platelets < 100,000/uL with splenomegaly or
             extensive bone marrow involvement as the etiology for their cytopenias are eligible

          -  Subjects must have adequate renal function with a creatinine clearance of >= 40 mL/min
             as determined by the Cockcroft-Gault calculation

          -  Total bilirubin =< 2 x upper limit laboratory normal (ULN); subjects with
             non-clinically significant elevations of bilirubin due to Gilbert's disease are not
             required to meet these criteria

          -  Serum transaminases aspartate aminotransferase (AST) (serum glutamic oxaloacetic
             transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate
             transaminase [SGPT]) =< 5 x ULN

          -  Serum alkaline phosphatase =< 5 x ULN

          -  Disease-free of prior malignancies for >= 2 years with the exception of basal or
             squamous cell skin carcinoma, carcinoma "in situ" of the breast or cervix, or
             localized prostate cancer (treated definitively with hormone therapy, radiotherapy, or
             surgery)

          -  Life expectancy of at least 3 months

          -  All study participants must be willing to be registered into the mandatory Revlimid
             REMS program after completion of induction chemoimmunotherapy and prior to maintenance
             therapy, and be willing and able to comply with the requirements of the Revlimid REMS
             program

          -  Subjects must not have a known history of hypersensitivity to mannitol

          -  Prior therapy with rituximab is permitted, even in the setting of rituximab-refractory
             disease

          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as
             required in the Revlimid REMS program

          -  Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (subjects
             intolerant to aspirin may use warfarin or low molecular weight heparin) if clinically
             indicated

          -  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 and again within 24
             hours prior to prescribing lenalidomide for cycle 1 (prescriptions must be filled
             within 7 days as required by the Revlimid REMS® program) 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 signing the informed consent document or complying with
             the protocol treatment

          -  Pregnant or breast-feeding females; lactating females must agree not to breast-feed
             while taking lenalidomide

          -  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

          -  Subjects are not eligible if there is a prior history or current evidence of central
             nervous system or leptomeningeal involvement

          -  Known hypersensitivity to thalidomide

          -  Concurrent use of other anti-cancer agents or treatments

          -  Known to be positive for human immunodeficiency virus (HIV) or infectious hepatitis
             (type B or C)

          -  Prior malignancy, except for adequately treated basal cell or squamous cell skin
             cancer, in situ cervical or breast cancer, or other cancer from which the subject has
             been disease free for at least 2 years

          -  Severe or life-threatening anaphylaxis or hypersensitivity reaction when previously
             exposed to rituximab or other monoclonal antibody therapy

          -  Chronic hepatitis B or hepatitis C infection

          -  New York Heart Association class 3-4 heart failure

          -  More than one grade 2 or higher transaminase elevation