This study has a phase 1 and a phase 2 component.

In phase 1, the objective is to determine the maximum tolerated dose (MTD) of lenalidomide when after azacitidine.

In phase 2, the objective is to determine the efficacy of the combination treatment.

The treatment regimen in this study is 7 day courses of azacitidine 75 mg/m2 followed by a 21-day courses of lenalidomide. For the primary objective, each 28-day cycle was repeated for a total of up to 6 cycles. Study completion was defined as 18 cycles of treatment, disease progression, or death.

In phase 1, the objective was to determine the maximum tolerated dose (MTD) of lenalidomide 5 mg, 10 mg, 25 mg or 50 mg, when administered after azacitidine.

In phase 2, the objective was to assess the efficacy of MTD lenalidomide administered after azacitidine, in up to six 28-day cycles.

Inclusion Criteria

• WHO-confirmed acute myeloid leukemia (AML), except acute promyelocytic leukemia (APL)

• White blood cell count (WBC) at initiation of treatment ≤ 10,000

  ◦If WBC is > 10,000 patients may be started on an appropriate dose of hydroxyurea (to be determined by the investigators), until WBC < 10,000, at which time the hydroxyurea will be discontinued for 24 hours prior to enrollment

• Age ≥ 60 years and not a candidate for allogeneic stem cell transplantation

• Unwilling or unable to receive conventional chemotherapy

• No prior therapy, except supportive care measures such as growth factor support, blood product transfusions, apheresis, or hydroxyurea

• ECOG performance status ≤ 2

• Life expectancy > 2 months

• All study participants must be registered into the mandatory RevAssist® program, and must be willing and able to comply with the requirements of RevAssist

• If a female of childbearing potential (FCBP):

  • 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 study enrollment and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days)
  • Must commit to either 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 starting lenalidomide.
  • Must also agree to ongoing pregnancy testing.
  • Male partners must use a latex condom during sexual contact, including if the male partners has previously had a successful vasectomy.

• Able to adhere to the study visit schedule and other protocol requirements

• Willing and able to understand and voluntarily sign a written informed consent

Exclusion Criteria

• Relapsed or refractory disease

• Prior therapy with lenalidomide

• History of intolerance to thalidomide or development of erythema nodosum while taking thalidomide or similar drugs

• Known or suspected hypersensitivity to azacitidine or mannitol

• Advanced malignant hepatic tumors

• Concomitant treatment with other anti-neoplastic agents, except hydroxyurea

• Anti-neoplastic treatment less than four weeks prior to enrollment, except 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

• If female:

  • Pregnant
  • Breast-feeding females, if they do not agree to not breastfeed while taking lenalidomide

• Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation

• Laboratory abnormalities:

  • Creatinine ≥ 1.5 mg/dL
  • Creatinine clearance ≤ 50 mL/min
  • Total bilirubin > 1.5 x institutional upper limit of normal (ULN), except documented Gilbert's syndrome
  • AST > 2.5 x institutional ULN
  • ALT > 2.5 x institutional ULN