Inclusion Criteria:

• Patient must be able to understand and voluntarily sign an informed consent form.
• Patient must be ≥ 18 years old.
• Patient must be able to adhere to the study visit schedule and other protocol requirements.
• Patient must have histologically confirmed Myelodysplastic Syndrome as defined by FAB Classification including CMML and secondary MDS which has either:
  • progressed at any time during treatment with hypomethylating agents
  • failed to achieve a response after 6 cycles
  • progressed after treatment with hypomethylating agents had been discontinued Criteria for response and for progression as defined by revised IWG criteria
• Patient must have discontinued all previous cancer therapy, including radiation, hormonal therapy and surgery at least 4 weeks prior to treatment in this study.
• Patient must have an ECOG performance status of ≤ 2 at study entry
• Patient must have laboratory test results within these ranges:
  • calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula
  • total bilirubin ≤ 1.5 x ULN
  • AST (SGOT) and ALT (SGPT) ≤ 3 x ULN
• Patient must be disease free of prior malignancies for at least 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
• Patient must be registered into the mandatory Revlimid REMS® program and be willing and able to comply with the requirements of Revlimid REMS®.
• If a female of childbearing potential (FCBP), patient must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 to 14 days prior to initiation of therapy and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days).
  
  Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. A FCBP is defined as a sexually mature woman who:
  • has not undergone a hysterectomy or bilateral oophorectomy; or
  • has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• If a FCBP, patient must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study:
  • for at least 28 days before starting study drug;
  • while participating in the study; and
  • for at least 28 days after discontinuation from the study. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods if needed

Exclusion Criteria:

• Patient must not have any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Patient must not be pregnant or breastfeeding.
• Patient must not have any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Patient must not use any other experimental drug or therapy within 28 days of baseline.
• Patient must not have a known hypersensitivity to thalidomide.
• Patient must not have developed of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Patient must not have any prior use of lenalidomide.
• Patient must not be concurrently using other anti-cancer agents or treatments.
• Patient must not have known seropositivity for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.