Inclusion Criteria:

- Understand and voluntarily sign an informed consent form

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

- Disease-specific criteria (Phase I):

- Previously untreated Acute Myeloid Leukemia (AML), associated with monosomy 5 or
segmental deletion involving 5q31, either alone or with additional cytogenetic
abnormalities

- Previously untreated AML (age ≥ 60 years)

- Myelodysplastic Syndrome, Refractory Anemia with Excess Blasts-2 (MDS,RAEB-2,
10-19% blasts in the bone marrow) associated with monosomy 5 or segmental
deletion involving 5q31, either alone or with additional cytogenetic
abnormalities

- For MDS, patients must have had progression with or failed response to
front-line therapy with a nucleoside analogue (azacitidine, decitabine).

- Disease Specific Criteria (Phase II)

- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry

- Left ventricular ejection fraction (LVEF) ≥ 50%

- Laboratory test results within these ranges:

- Serum creatinine ≤ 2.0 mg/dL

- Total bilirubin ≤ 1.5 mg/dL (Gilbert's syndrome excluded)

- Aspartic transaminase (AST) and Alanine transaminase (ALT) ≤ 2 x upper limit of
normal (ULN)

- Disease free of prior malignancies for ≥ 2 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix
or breast

- Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to
and again within 24 hours of starting lenalidomide. For FCBP who have a medical need
to proceed with therapy immediately, the pregnancy test that would normally be done
10-14 days prior to initiation of lenalidomide may be done as late as 7 days prior to
initiation of lenalidomide. Both this test and the pregnancy testing done within 24
hours prior to initiation of lenalidomide must be negative. FCBP 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. All patients
must be counseled at a minimum of every 28 days about pregnancy precautions and risks
of fetal exposure. *For patients who have latex allergies or whose partner(s) have
latex allergies, alternatives will be discussed.

- Must be able to swallow capsules and no evidence of gastrointestinal (GI) tract
abnormality that would alter absorption of oral medications

- Understand and voluntarily sign an informed consent form

- Life expectancy >3 months

- All study patients 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 within 10 - 14 days and again
within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be
filled within 7 days as required by RevAssist) 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: Risks of
Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

Exclusion Criteria:

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the patient from signing the informed consent form

- Pregnant or breast feeding females. (Lactating females must agree not to breast feed
while taking lenalidomide).

- Unwilling or unable to participate with Food and Drug Administration (FDA) mandated
birth control and pregnancy guidelines

- Any condition, including the presence of laboratory abnormalities, which places the
patient at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study

- Use of any other experimental drug or therapy within 28 days of baseline

- Known hypersensitivity to thalidomide

- The development of erythema nodosum, if characterized by a desquamating rash, while
taking thalidomide or similar drugs

- Any prior use of lenalidomide

- AML with cytogenetics including t(15;17), t(8;21), or inv(16)

- White blood count (WBC) count ≥ 50,000 on hydroxyurea therapy

- Previous history of induction chemotherapy for AML or allogeneic stem cell transplant

- Predicted inability to tolerate standard induction chemotherapy with idarubicin and
cytarabine

- History of spontaneous thromboembolic event requiring use of anticoagulation with
warfarin (coumadin) or low molecular-weight heparin within 3 years

- Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type
A, B or C