A Trial to Evaluate Two Schedules of MS275 in Combination With 5AC in Elderly Patients With Acute Myeloid Leukemia (AML)

Inclusion Criteria:

1. One of the following:

   Untreated AML in (de novo or treatment related) patients in the following categories:
   * Medical conditions that compromise the ability to give cytotoxic chemotherapy as the primary modality.
   * Patients who decline cytotoxic chemotherapy.

   Patients with AML who have relapsed despite one prior regimen
2. ECOG performance status 0, 1, or 2
3. Patients must not have untreated active infections at the time of study entry.
4. Normal organ function as defined below:

   * Creatinine \< 2 mg/dl.
   * Total serum bilirubin within institutional limits unless due to hemolysis, Gilbert's syndrome, or ineffective erythropoiesis.
   * AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal.
5. Life expectancy of at least three months.
6. Patients must be informed of the investigational nature of the treatment, results that might be expected, and potential toxicities. They must be able to understand and give informed written consent according to federal and institutional guidelines.
7. Declined or ineligible for potentially curative options such as allogeneic stem cell transplant.
8. No chemotherapy or study drugs for \>3 weeks prior to starting study.
9. Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment. All men and women of childbearing potential must use acceptable methods of birth control throughout the study as described below:

   * Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study. Adequate forms of contraception are double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation.
   * Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study or to abstain.

Exclusion Criteria

1. Any of the Following:

   * Treatment for acute myeloid leukemia (AML), including hematopoietic growth factors, \< 3 weeks prior to study registration. Exception: Hydroxyurea may be administered to patients with WBC \> 30,000/µL
   * Diagnosis of acute promyelocytic leukemia (APL)
   * Radiotherapy \< 4 weeks prior to study registration
   * Failure to recover (to \< grade 1) from all adverse events associated with prior therapy.
   * Valproic acid \< 2 weeks prior to study registration.
   * Hypersensitivity to azacytidine, deoxyazacytidine, mannitol, entinostat or components of the entinostat tablet
   * Any advanced malignant hepatic tumor(s)
2. Prior therapy with demethylating agents for leukemia treatment within the last four months.
3. Clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or central nervous system leukemia.
4. Serious or uncontrolled medical conditions.
5. Concurrent use of any other investigational agents.
6. Known HIV-positive patients.
7. Pregnancy or breast feeding
8. Male and female patients who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence) to avoid pregnancy during the study and for a minimum of 30 days after study treatment.