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