A Randomized Phase II Study of Azacitidine in Combination with Lenalidomide (NSC-703813) vs. Azacitidine Alone vs. Azacitidine in Combination with Vorinostat (NSC-701852) for Higher-Risk Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

-Pts must have morphologically confirmed MDS or CMML by FAB, WHO or IPSS score; AML pts are not eligible. (Procedures for establishing baseline disease must be done within 30 days prior to reg.)
-Pts must not have received lenalidomide, azacitidine, vorinostat or decitabine as treatment previously. Hem growth factors must be stopped >/= 14 days prior to reg. Pts may have received low dose cytarabine for MDS treatment previously, but must have stopped its use for >/= 28 days prior to reg.
-Patients must not have received radiation therapy, chemotherapy, or cytotoxic therapy to treat conditions other than MDS within 12 months prior to registration.
-Pts must not have undergone prior allo stem cell or bone marrow transplantation at any time.
-Pts must not have received > physiologic doses of a corticosteroid agent within 28 days prior to reg.
-Pts must be >/= 18 years of age.
-Pts must have Zubrod Performance Status of 0-2.
-Pretreatment cytogenetics must be performed on all patients. Collection of pretreatment specimens must be completed within 30 days prior to reg.
-Pts must be offered participation in specimen banking
-Pts must not have any pre-existing neurotoxicity/neuropathy of �� Grade 2 by CTCAE 4.0, or prior �� Grade 3 allergic reaction/hypersensitivity or rash to thalidomide, that has not resolved to < Grade 2.
-Pts must not have any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent.
-Pts must not have history of thromboembolic event or other condition requiring current use of anticoagulation with coumadin (warfarin) or low molecular-weight heparin.
-Pts must not have known or suspected hypersensitivity to mannitol.
-Pts must not have used or be using HDAC inhibitor agents for anticancer treatment.
-Pts may not have received agents such as valproic acid for epilepsy within 30 days prior to reg.
-Patients must receive a 12-lead EKG, chest x-ray, serum creatinine, complete metabolic panel including SGOT or SGPT, electrolytes, and bilirubin testing within 28 days prior to reg.
-Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test (sensitivity >/= 25 mIU/mL) within 10 �C 14 days prior to reg and must agree to have a second pregnancy test within 24 hours prior to starting Cycle 1 if randomized to receive lenalidomide. Further, patients commit to the outlined contraception and education/counseling for lenalidomide.
-No prior malignancy is allowed except for adequately treated basal (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease free for three years.
-All pts must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.