Treatment of Chronic Lymphocytic Leukemia in Patients Previously Exposed to Rituximab

Inclusion Criteria:

1. Subjects must have confirmed diagnosis of chronic lymphocytic leukemia (CLL).
2. Prior therapy with at least one regimen containing rituximab
3. Age \> 18 years.
4. Life expectancy greater than 12 months.
5. ECOG performance status \<2
6. Patients must have normal organ function as defined in the protocol.
7. Patients must have adequate bone marrow function as defined in the protocol.
8. Ability to understand and the willingness to sign a written informed consent document.
9. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
10. 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 prior to 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.
11. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin.

Exclusion Criteria:

1. Patients who have had chemotherapy or radiotherapy within 4 weeks or received any monoclonal antibody within 6 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
2. Patients may not be receiving any other investigational agents or other anti-cancer agents or treatments.
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ofatumumab or lenalidomide.
4. Uncontrolled concomitant illness.
5. Pregnant women are excluded from this study because lenalidomide is believed to be teratogenic.
6. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ofatumumab or lenalidomide.
7. Prior treatment with lenalidomide
8. Evidence of laboratory TLS by Cairo-Bishop Definition of Tumor Lysis Syndrome. Subjects may be enrolled upon correction of electrolyte abnormalities.
9. All patients will undergo screening for hepatitis B and may or may not be eligible based on the results as outlined in the protocol.