Idarubicin + Cytarabine and Lenalidomide in Patients With Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML)

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