Mitoxantrone, Etoposide, and Cytarabine (MEC) Plus Lenalidomide for Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria: * Acute myelogenous leukemia diagnosed by WHO criteria with one of the following (patients with biphenotypic leukemia are eligible, provided that the treating physician determines an AML treatment regimen is appropriate) * Primary refractory disease following \> 1cycle of chemotherapy, (such as hypomethylating agent or induction chemotherapy) * First relapse or higher. Patients with primary or secondary acute myelogenous leukemia are eligible. * Age 18-70 years old * LVEF \> 50 % * ECOG Performance status 0-2 * Able to adhere to study schedule and other protocol requirements. * Participants must have normal organ function as defined below, unless felt due to underlying disease and approved by the overall PI. Patients with Gilbert's disease may have total bilirubin up to \< 3 x ULN. * Creatinine \< 2.0mg/dl * Total bilirubin \< 1.5 x ULN * AST (SGOT) and ALT (SGPT) \< 3 x ULN. * Patients may receive hydroxyurea, steroids, or leukapheresis as necessary until Day 5 of treatment. * Patients must give voluntary written informed consent and HIPAA authorization before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. * Patients may have had prior treatment for MDS or AML, including prior lenalidomide for MDS or AML or another condition. * Patient may have had prior autologous or allogeneic transplant (family member, unrelated donor, or cord blood) if there is at least 90 days between transplant and study entry. * Patients may also have had donor lymphocyte infusion if there is at least 60 days between donor lymphocyte infusion and study entry. * Patients on immunosuppression are also eligible. * Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL prior to receiving treatment with lenalidomide, 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. * Ability to understand and the willingness to sign a written informed consent document. * All study participants must be registered into the mandatory Revlimid REMS ® program, and be willing and able to comply with the requirements of the REMs ® program. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program Exclusion Criteria: * Known hypersensitivity to thalidomide or lenalidomide (if applicable). * The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. * Known seropositive for human immunodeficiency virus (HIV). HIV testing is not required. Hepatitis testing is not required. * Patients who have had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. * Any serious medical condition laboratory abnormality or psychiatric illness that would prevent the subject from signing the consent form. * Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Patients with major surgery within 28 days prior to treatment. * Patients with any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol. * Patient has received an investigational agent or cytotoxic chemotherapy (excluding hydroxyurea) within 7 days of study entry. * Patients with acute promyelocytic leukemia. * Females who are pregnant