Phase II Protocol for CLL With Fludarabine and Cyclophosphamide With Rituximab (FCR) Plus Lenalidomide

Inclusion Criteria

• Patients must have diagnosis of CLL (as defined by the NCI Criteria below:
• Patients must have peripheral blood absolute lymphocyte count of >5,000/mm3 obtained within 2 weeks prior to start of study.
• The lymphocytosis must consist of small, mature lymphocytes, with ≤55% (not greater than 55%) prolymphocytes.
• Patients must have phenotypically characterized CLL as defined as:
• The predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.);
• Surface immunoglobulin (slg) and CD20 with low-cell surface density expression.
• If surface immunoglobulin can be demonstrated, the leukemic cells are restricted to expression of either kappa or lambda.
• Splenomegaly, hepatomegaly or lymphadenopathy are not required for the diagnosis of CLL
• Patients must require chemotherapy
• Patients must not have received prior treatment cytotoxic, immunotherapy or investigational therapy.
• Patients must not have history of corticosteroid treatment for CLL, Autoimmune thrombocytopenia, or autoimmune hemolytic anemia.
• Calculated creatinine clearance ≥30ml/min by Cockcroft-Gault formula
• Bilirubin must be ≤1.5mg/dl, unless secondary to tumor, obtained within 2 weeks prior to registration
• Platelets ≥75x109/L, unless due to CLL involvement of bone marrow
• Neutrophils ≥1.5x109/L, unless due to CLL involvement of bone marrow
• AST or ALT < 2x upper limit of normal, unless related to CLL
• Age ≥18 years
• ECOG performance status 0-2
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test
• Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
• Able to take aspirin (81mg or 325mg) daily as prophylactic anticoagulation
• Subject must provide written informed consent
• All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®

Exclusion Criteria

• Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia are not eligible
• No prior immunotherapy, investigational or cytotoxic chemotherapy
• Patients with a history of steroid treatment for CLL/SLL autoimmune hemolytic anemia, or autoimmune thrombocytopenia are not eligible
• Patients with active infections requiring oral or intravenous (IV) antibiotics until resolution of the infection and completion of therapeutic antibiotics
• Women of childbearing potential and sexually active males who both refuse to use an accepted and effective method of contraception or women who are breastfeeding
• Patients with a second malignancy other than basal cell carcinoma or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are not eligible unless the tumor was treated with curative intent at least two years previously
• History of known HIV
• History or presence CNS disease
• Evidence of laboratory TLS by Cairo-Bishop definition of Tumor Lysis Syndrome
• History of corticosteroid treatment for CLL, Autoimmune thrombocytopenia, or autoimmune hemolytic anemia.