Azacitidine Plus Lenalidomide Combination in Elderly Patients With Previously Treated AML and High-Risk MDS (VIREL2 Trial)

Inclusion Criteria:

To be eligible to participate in this study, a patient must meet the following criteria
(at the principal investigators' discretion):

- AML (according to the WHO 2008 classification), including:

- de novo or secondary AML previously treated with demethylating agents for AML

- secondary AML previously treated with demethylating agents for MDS

- de novo or secondary AML previously treated with high dose lenalidomide for AML
(>=25mg)

- High Risk MDS, including

- Del (5q) and non-del (5q), previously treated with lenalidomide.

- novo or secondary HR-MDS previously treated with demethylating agents

- White blood cell count (WBC) at initiation of treatment <= 10,000

o 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 and not an immediate candidate for allogeneic stem cell transplantation

- Unwilling or unable to receive conventional chemotherapy

- Prior therapy, with either single agent demethylator (5-Azacitidine or Decitabine)
and/or Lenalidomide

- ECOG performance status <= 2 (See Appendix C for definitions)

- Life expectancy >= 2 months

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

- Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL 10-14 days prior to study
enrollment and again within 24 hours of prescribing lenalidomide (prescriptions must
be filled within 7 days) 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. Men must agree to use a latex condom during sexual contact with a
FCBP even if they have had a successful vasectomy. (See Appendix A: Risks of Fetal
Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods).

- 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 meeting any of the following criteria will be excluded from this study:

- Patients with LR-MDS (low-risk Myelodysplastic Syndromes) progressing to HR-MDS after
low dose lenalidomide or 5-day azacitidine will not be eligible.

- History of intolerance to thalidomide or 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 or breast feeding females; lactating females must agree not to breast feed
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:

- Either creatinine >=1.5 mg/dL or creatinine clearance <=50 mL/min

- Total bilirubin >= 1.5 x institutional ULN (Upper limit of normal) (unless
documented Gilbert's syndrome)

- AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase) >= 2.5 x
institutional ULN