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