Inclusion Criteria:

1. One of the following:

Untreated AML in (de novo or treatment related) patients of age > 60 years 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 of age ≥ 60 years who have relapsed despite one prior regimen

2. ECOG performance status 0, 1, or 2 (see Appendix A).

3. Age > 60 years

4. Patients must not have untreated active infections at the time of study entry.

5. 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.

6. Life expectancy of at least three months.

7. 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.

8. Declined or ineligible for potentially curative options such as allogeneic stem cell
transplant.

9. No chemotherapy or study drugs for >3 weeks prior to starting study.

10. 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 AML, including hematopoietic growth factors, < 3 weeks prior to
study registration. Exception: Hydroxyurea may be administered to patients with
WBC > 30,000/µL (see Section 8)

- 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 year.

3. Clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular
coagulation, or CNS 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.