Inclusion Criteria:

1. Patients with B-cell CLL with indications for treatment by National Cancer Institute (NCI) Working Group criteria or Rai Stage III or IV
2. Patients who have received a minimum of one prior purine analog-based chemotherapy regimen. Prior treatment with corticosteroids, immunotherapy, monoclonal antibody or radiation therapy is permitted. All previous cancer therapies, including radiation, hormonal therapy and surgery must have been discontinued 2 weeks prior to treatment in this study. Any cytotoxic chemotherapy must be discontinued 4 weeks prior to treatment in this study.
3. Age more than or equal to 18 years (CLL is not observed in patients less than 18 years of age)
4. Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status 0-2
5. Adequate renal function indicated by serum creatinine less than or equal to 2 and adequate hepatic function indicated as total bilirubin less than or equal to 2 times the upper limit of normal
6. Understand and sign Informed Consent after the investigational nature, study design, risks and benefits of the study have been explained
7. Women of child-bearing potential (WCBP): A woman of child-bearing potential (a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months, i.e., who has had menses at any time in the preceding 24 consecutive months) must have a negative urine pregnancy test within 7 days of starting study drug.
8. (Continued from #7) In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or abstinence) while on study drug. A man must agree not to father a child and agree to use a condom if his partner is of child-bearing potential, even if he has had a successful vasectomy.
9. Disease free of prior malignancies for 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.

Exclusion Criteria:

1. Known sensitivity to thalidomide or its derivatives
2. The development of erythema nodosum as characterized by a desquamating rash while taking thalidomide or similar drugs.
3. Prior use of lenalidomide
4. Concurrent use of other anti-cancer agents or treatment
5. Known positivity for HIV or infectious hepatitis type A, B or C
6. Pregnant or lactating females
7. A serious medical condition, laboratory abnormality or psychiatric illness that would pose unacceptable risk to the subject if he/she were to participate in the study or that would interfere with the ability of the patient to carry out the treatment program or confine the ability to interpret the data from the study.
8. Documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood)
9. Active cardiovascular disease as defined by the New York Heart Association class 3 or 4.