Clofarabine Followed By Lenalidomide for High-Risk Myelodysplastic Syndromes and Acute Myeloid Leukemia

* INCLUSION CRITERIA:
* Age greater than or equal to 18 years old
* Unequivocal diagnosis of MDS (including chronic myelomonocytic leukemia- CMML) according to WHO criteria with IPSS risk categorization for MDS subjects of intermediate-2 to high confirmed by bone marrow evaluation within 30 days prior to study enrollment

OR

Unequivocal diagnosis of AML according to WHO criteria to include secondary and relapsed or refractory disease confirmed by bone marrow evaluation within 30 days prior to study enrollment

* ECOG Performance Status less than or equal to 2
* Must have failed at least one prior therapy before study enrollment
* Ability to comprehend the investigational nature of the study and provide informed consent
* All study participants must be registered into the mandatory RevAssistRevlimid REMS program, and be willing and able to comply with the requirements of RevAssistRevlimid REMS .
* 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 and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by RevAssistRevlimid REMS ) 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. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMSTM program. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

EXCLUSION CRITERIA:

* Prior Allogeneic Stem Cell Transplant
* Diagnosis of acute promyelocytic leukemia
* Diagnosis of atypical chronic myeloid leukemia BCR-ABL1 negative, juvenile myelomonocytic leukemia, yelodysplastic/myeloproliferative neoplasm unclassifiable)
* Prior therapy with clofarabine at any dose
* Prior therapy with lenalidomide at doses greater than or equal to 25 milligrams daily
* Clinically significant active infection not responding adequately to therapy
* HIV Positive
* Uncontrolled concurrent hepatic, renal, cardiac, pulmonary, neurologic, infectious, or metabolic disease of such severity, which in the opinion of the PI, would preclude the subjects s ability to tolerate protocol therapy
* Ejection fraction less than 40% by Echocardiogram or MUGA
* Calculated creatinine clearance less 60 milliliters per minute
* Serum bilirubin greater than 1.5 times upper limit of normal
* Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) greater than 3 times upper limit normal
* Decreased oxygen saturation at rest (e.g. pulse oximeter less than 88% or PaO2 less than or equal to 55 millimeters of mercury)
* Patients with any condition that prevents their ability to swallow and retain lenalidomide tablets
* Severe psychiatric illness or complex social situations that would limit the patient s ability to tolerate and/or comply with study requirements
* Current pregnancy or breastfeeding