Velcade and Lenalidomide in Patients With Relapsed AML and MDS After Allogeneic Stem Cell Transplantation

Inclusion Criteria: * Participants must meet the following criteria on screening examination to be eligible to participate in the study: * A diagnosis of recurrent, persistent, or progressive acute myelogenous leukemia (AML), defined as \>= 5% blasts in a patient with known prior history of AML, or recurrent, persistent, or progressive myelodysplastic syndrome (MDS) according to WHO criteria. * Must have undergone an allogeneic SCT (regardless of stem cell source) * Patients must be 18 years or older * Able to adhere to study schedule and other protocol requirements * Must be off all immunosuppressive medications (except prednisone) for at least 2 weeks prior to study entry. * Must be on less than 21 mg of oral prednisone daily for GVHD * ECOG performance status 0-2 (see Appendix 2) * Participants must have the following organ function all within 21 days prior to enrollment * Total bilirubin ≤ 2.0 mg/dl unless due to underlying conjugation disease such as Gilbert's * ALT and AST ≤ 3X the upper limit of normal * Creatinine \< 2.0 mg/dl * Patients may receive hydroxyurea or leukopheresis as necessary * Patients must give voluntary written informed consent and HIPA authorization before performance of any study-related procedure not part of normal medical care with the understanding that consent maybe withdrawn by the subject at any time without prejudice to future medical care. * All previous cancer therapy including donor lymphocyte infusions must have been discontinued at least 2 weeks prior to treatment in this study. * All study participants must be registered in the RevREMS® program and be willing and able to comply with the requirements of REMS® program. * Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. Exclusion Criteria: * Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study. * Ejection fraction \< 40% obtained by either MUGA or echocardiogram * Patients who had had a myocardial infarction within 6 months of enrollment or have 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. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant. * 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 an 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 trial enrollment * Patients with greater than or equal to grade 2 peripheral neuropathy or active herpes infection * Patients with ≥ grade 3 acute graft-versus-host disease are excluded from the study * Patients with moderate or severe chronic graft-versus host requiring more than 20 mg of oral prednisone therapy are excluded from the study. * Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cirrhosis, chronic obstructive or restrictive pulmonary disease, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia * Patients with any serious or medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol * Female subject is pregnant or breast-feeding. Lactating females must agree not to breastfeed while taking lenalidomide. * Patient has received an investigational drug within 14 days of enrollment * Known hypersensitivity to thalidomide or lenalidomide * Known hypersensitivity to Velcade, boron, or mannitol * The development of erythema nodosum as characterized by desquamating rash while taking thalidomide or similar drugs * Concurrent use of other anti-cancer agents or treatment * Known positive for HIV * Diagnosed or treated for a non-hematologic malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy. * Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.