• To determine the overall clinical benefit of Revlimid® in chemotherapy-naïve AIPC. The overall clinical benefit is defined as the sum of complete response, partial response, and stable disease. [ Time Frame: 24 months for acrual ] [ Designated as safety issue: No ]
  

• Toxicity and tolerability, time to disease progression, to systemic chemotherapy and alternative therapy. Changes in PSA-Doubling time before treatment versus after treatment with Revlimid®. Maximum confirmed change in PSA from pre-treat. [ Time Frame: 24 months for acrual ] [ Designated as safety issue: Yes ]
  

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.
2. Age 18 years at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Documented prostate cancer regardless of Gleason score
5. Patients should be considered hormone refractory and androgen independent. They must fail LHRH analogues, and anti-androgen withdrawal trial. Failure is confirmed by an increase in PSA value of 10% or more than the value immediately before, and confirmed by another assessment 2 weeks later that shows a further increase.
6. Patients must have measurable disease either biochemically (using PSA) and/or using the RECIST criteria for visceral organ involvement and/or bone disease
7. ECOG Performance Status of 2 or less.
8. Adequate liver function tests with ALT/AST being < 3x normal, total bilirubin of 1.5 or less, and adequate renal function measured by a creatinine of 2.0 mg/dl or less. Alkaline phosphatase values are never exclusion criteria if it is deemed related to bone metastases.

9. Patients need to have adequate bone marrow function.

   • ANC of 1000 or above,
   • Hgb of 9.0 g/dl or above,
   • Platelets of 100,000 or above. If other causes are affecting plts counts such as autoimmune disorders, patients are allowed on study. Patients with inadequate bone marrow function that is deemed related to bone marrow involvement with prostate cancer are allowed at the investigator's discretion.
10. Patients with other malignancies are allowed as long as there is no evidence of the other malignancy present at entry time, and it has been 3 years or more since the treatment for the other disorder was completed.
11. Patients with prior exposure to investigational therapies including vaccines are allowed on this study as long as their last exposure was 4 weeks prior to study entry. Erlotinib exposure and GM-CSF is not an exclusion criteria as it is not considered chemotherapy.
12. Patients with known bone metastases are allowed to receive intravenous bisphosphonates such as aredia or zometa. Patients on oral bisphosphonates are also allowed.
13. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
14. Patients must agree to use a latex condom during sexual contact with a female of childbearing potential, even if they have had a successful vasectomy. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
15. 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. Prior systemic chemotherapy for AIPC. Investigational therapy such as vaccines, immunotherapy, and oral targeted agents such as erlotinib, sorafenib, or sunitinib are allowed.
2. Prior exposure to lenalidomide
3. Known HIV positive status
4. Known brain metastases.
5. Steroids are allowed concomitantly ONLY IF they are taken for another chronic medical condition (Such as COPD, Multiple sclerosis…etc)
6. Presence of other malignancies, unless the last treatment received for any other malignancy was 3 years or more. Non-melanoma skin cancers are excluded.
7. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
8. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he were to participate in the study or confounds the ability to interpret data from the study.
9. Use of any other experimental drug or therapy within 28 days of baseline.
10. Known hypersensitivity to thalidomide.
11. Known positive for HIV or infectious hepatitis, type A, B or C