Azacitidine + Lenalidomide Combo in the Elderly With Previously Treated AML & High-Risk MDS

Inclusion Criteria: * acute myeloid leukemia (AML) (according to the WHO 2008 classification): * De novo * Secondary AML previously treated with demethylating agents for AML * Secondary AML previously treated with demethylating agents for MDS * Secondary AML previously treated with high dose lenalidomide for AML (≥ 25mg) * High Risk MDS: * Del (5q) * Non-del (5q), previously-treated with lenalidomide. * Novo or secondary HR-MDS previously treated with demethylating agents * White blood cell (WBC) ≤ 10,000 * Age ≥ 60 * Not an immediate candidate for allogeneic stem cell transplantation * Unwilling or unable to receive conventional chemotherapy * Prior therapy: * with single agent demethylator (5-Azacitidine or Decitabine) * with Lenalidomide * Eastern Cooperative Oncology Group performance status ≤ 2 * Life expectancy \> 2 months * All study participants must be registered into the mandatory RevAssist program * Willing and able to comply with the requirements of RevAssist * Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test 10-14 days prior to study enrollment and again within 24 hours of prescribing lenalidomide * Must commit to either continued abstinence from intercourse or begin two acceptable methods of birth control, at least 28 days before she starts taking lenalidomide. * 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. * Willing and able to understand and voluntarily sign a written informed consent * Able to adhere to the study visit schedule and other protocol requirements Exclusion Criteria: * Patients with LR-MDS progressing to HR-MDS after low dose lenalidomide or 5-day azacitidine will not be eligible. * History of intolerance to thalidomide -development of erythema nodosum while taking thalidomide or similar drugs * Known or suspected hypersensitivity to azacitidine or mannitol * Patients with advanced malignant hepatic tumors. * Concomitant treatment with other anti-neoplastic agents, with the exception of hydroxyurea * Previous participation on the VIREL study with the concomitant use of azacitidine plus lenalidomide. * Anti-neoplastic treatment less than four weeks prior to enrollment, with the exception of hydroxyurea * Use of any other experimental drug or therapy within 28 days of baseline * Inability to swallow or absorb drug * Active opportunistic infection or treatment for opportunistic infection within four weeks of first day of study drug dosing * New York Heart Association Class III or IV heart failure * Unstable angina pectoris * Uncontrolled cardiac arrhythmia * Uncontrolled psychiatric illness that would limit compliance with requirements * Known HIV infection * Pregnant * Breast feeding * Lactating females must agree not to breast feed while taking lenalidomide * Other medical or psychiatric illness or organ dysfunction or laboratory abnormality * Laboratory abnormalities: * Either creatinine ≥ 1.5 mg / dL or creatinine clearance ≤ 50 mL / min * Total bilirubin \>1.5 x institutional ULN * AST and ALT \> 2.5 x institutional ULN