"A Genetic Risk-Stratified Randomized Phase II Study of Four Fludarabine/Antibody Combinations for Patients with Symptomatic, Previously Untreated Chronic Lymphocytic Leukemia."

Pts must have diagnosis of B-Cell CLL, absolute lymphocytosis > 5,000/mcl, prolymphocytes < 55%. Bone marrow exam must include a unilateral aspirate and biopsy; aspirate smear must show > 30% of all nucleated cells to be lymphoid OR biopsy must show lymphoid infiltrates compatible with marrow involvement by CLL. Overall cellularity must be normocellular or hypocellular. Lymphocyte phenotype must show predominant B-cell monoclonal population sharing B-cell marker (CD19, CD20, CD23) with CD5 antigen in absence of other pan-T-cell markers. B-cells must be monoclonal with regard to expression of kappa or lambda and have surface immunoglobulin expression of low density. Pts with bright surface immunoglobulin levels must have CD23 co-expression. Pts must have symptomatic and active intermediate or high-risk categories of the modified Rai staging system; pts in the intermediate-risk group must have evidence of active disease. Pts must not have had prior therapy for CLL (including corticosteroids for autoimmune complications that have developed since initial CLL diagnosis). Pts must not have medical condition requiring chronic use of corticosteroids. Pts must be >/= 18 yrs. Pts must have PS 0-2. Pts with HIV infection must meet additional criteria outlined. Pts must not be pregnant or nursing. Women of child-bearing potential randomized to Arm B must have a negative serum or urine pregnancy test; men randomized to Arm B must agree not to father a child during the study and for 4 weeks after stopping lenalidomide. All pts on Arm B must agree to use acceptable contraception and must be counseled at least every 28 days about pregnancy precautions and fetal exposure risk. Pts must have creatinine </= 1.5 x IULN.