Azacitidine With or Without Lenalidomide or Vorinostat in Treating Patients With Higher-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

Inclusion Criteria:

   - Patients must have morphologically confirmed diagnosis of myelodysplastic syndrome
   (MDS) or chronic myelomonocytic leukemia (CMML) based on one of the following:

      - French-American-British (FAB) classifications:

         - Refractory anemia with excess blasts (RAEB - defined as having 5-20%
         myeloblasts in the bone marrow)

         - Chronic myelomonocytic leukemia (CMML) with 10-19% myeloblasts in the bone
         marrow and/or 5-19% blasts in the blood

      - World Health Organization (WHO) classifications:

         - Refractory anemia with excess blasts-1 (RAEB-1 - defined as having 5-9%
         myeloblasts in the bone marrow)

         - Refractory anemia with excess blasts-2 (RAEB-2 - defined as having 10-19%
         myeloblasts in the bone marrow and/or 5-19% blasts in the blood)

         - Chronic myelomonocytic leukemia-1 (CMML-1 - defined as having < 10%
         myeloblasts in the bone marrow and/or < 5% blasts in the blood)

         - Chronic myelomonocytic leukemia-2 (CMML-2 - defined as having 10-19%
         myeloblasts in the bone marrow and/or 5-19% blasts in the blood) OR

      - International prognostic score (IPSS) of intermediate 2 (1.5-2.0 points) or high
      (>= 2.5 points); a score of intermediate 1 (0.5-1.0 points) is only allowable in
      the setting of >= 5% myeloblasts

      - NOTE: Patients with acute myeloid leukemia (AML) are not eligible

      - Procedures to obtain specimens for establishing baseline disease must be done
      within 30 days prior to registration

   - Patients must not have received lenalidomide, azacitidine, vorinostat, or decitabine
   as treatment previously; any hematopoietic growth factors must be stopped for at least
   14 days prior to registration; patients may have received low-dose cytarabine for MDS
   treatment previously, but they must have discontinued its use for at least 28 days
   prior to registration; patients may have received prior hydroxyurea per CMML treatment
   previously, but they must have discontinued its use for at least 7 days prior to
   registration; these patients will not be eligible if white blood cell (WBC) >
   30,000/mm^3

   - Patients must not have received radiation therapy, chemotherapy, or cytotoxic therapy
   to treat conditions other than MDS within 12 months prior to registration

   - Patients must not have undergone prior allogeneic stem cell or bone marrow
   transplantation at any time; patients that have undergone an autologous stem cell
   transplant are eligible

   - Patients must not have used or be using histone deacetylase (HDAC) inhibitor agents
   for anticancer treatment

   - Patients may not have received agents such as valproic acid for epilepsy within 30
   days prior to registration

   - Patients must have Zubrod performance status of 0-2

   - Patients must not have any pre-existing neurotoxicity/neuropathy of >= grade 2
   according to the National Cancer Institute (NCI) Common Toxicity Criteria version 4.0,
   or prior >= grade 3 allergic reaction/hypersensitivity or rash to thalidomide, that
   has not resolved to < grade 2

   - Patients 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

   - Patients must not have history of thromboembolic event or other condition requiring
   current use of anticoagulation with Coumadin (warfarin) or low molecular-weight
   heparin

   - Patients must not have known or suspected hypersensitivity to mannitol

   - Patients must receive a 12-lead electrocardiogram (EKG), chest x-ray or computed
   tomography (CT) scan, serum creatinine, complete metabolic panel including serum
   glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase
   (SGPT), electrolytes, and bilirubin testing within 28 days prior to registration in
   order to establish baseline measurements; questions regarding patient safety in
   regards to results of these tests should be directed to the study chair

   - Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
   test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to
   registration; FCBP 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 following if they are randomized to receive
      lenalidomide: 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 starting 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; a FCBP is a sexually mature woman
      who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not
      been naturally postmenopausal for at least 24 consecutive months (i.e., has had
      menses at any time in the preceding 24 consecutive months); all patients must be
      counseled by a trained counselor every 28 days about pregnancy precautions and
      risks of fetal exposure

      - NOTE: Patients not randomized to receive lenalidomide will not be required to
      undergo serial pregnancy testing or lenalidomide counseling after registration

   - No prior malignancy is allowed except for adequately treated basal cell (or squamous
   cell) skin cancer, in situ cervical cancer, or other cancer for which the patient has
   been disease-free for three years

   - Cytogenetics requirements:

      - Southwestern Oncology Group (SWOG) (and other sites not affiliated with Alliance
      or Eastern Cooperative Oncology Group [ECOG]-American College of Radiology
      Imaging Network [ACRIN]): Pretreatment cytogenetics must be performed on all
      patients; collection of pretreatment specimens must be completed within 30 days
      prior to registration to S1117; specimens must be submitted to the site's
      preferred Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics
      laboratory; reports of the results must be submitted as described; note that
      cytogenetics are required at other timepoints; NOTE: National Cancer Institute of
      Canada Clinical Trials Group (NCIC CTG) sites may submit specimens to College of
      American Pathologists (CAP) or Ontario Laboratory Accreditation (OLA)-approved
      laboratories providing the lab is licensed to perform fluorescent in situ
      hybridization (FISH) analysis

      - Alliance: Alliance patients must enroll on Cancer and Leukemia Group B (CALGB)
      8461, the cytogenetics protocol; CALGB 8461 provides sample procurement and
      submission instructions to Alliance-approved institutional cytogeneticists; note
      that cytogenetics are required at other timepoints

      - ECOG-ACRIN: Pretreatment cytogenetics must be performed on all patients;
      collection of pretreatment specimens must be completed within 30 days prior to
      registration to S1117; specimens must be submitted to the site's preferred
      CLIA-approved cytogenetics laboratory; karyotypes and reports must be submitted
      for review to the Mayo Clinic Cytogenetics Laboratory in Rochester; note that
      cytogenetics testing is required at other timepoints

   - Banking requirements:

      - SWOG, Alliance and ECOG-ACRIN (and other sites not affiliated with NCIC CTG):
      Patients must be offered participation in specimen banking; with patient consent,
      specimens must be submitted as outlined

      - Alliance: (Temporarily Closed 2/28/14): As of February 28, 2014, CALGB 9665 has
      been temporarily closed, so Alliance patients under consideration for S1117 are
      NOT to be registered to CALGB 9665 and no specimens for patients enrolled after
      February 28, 2014 are to be submitted via this ancillary study; these patients
      should submit specimens per SWOG instructions; patients already enrolled on CALGB
      9665 should continue to submit specimens per instructions in CALGB 9665

      - NCIC CTG: NCIC CTG patients must be offered participation in specimen submission
      and banking; with patient consent, specimens must be submitted as outlined

   - All patients or their legally authorized representative 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

   - As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
   treating institution's identity is provided in order to ensure that the current
   (within 365 days) date of institutional review board approval for this study has been
   entered in the system