A Randomized Phase II Trial of Azacitidine With or Without the Histone Deacetylase Inhibitor Entinostat for the Treatment of Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia (Dysplastic Type), and Acute Myeloid Leukemia With Multilineage Dysplasia

Inclusion Criteria:

- Bone marrow aspirate and/or biopsy-confirmed diagnosis of 1 of the following:

- Myelodysplastic syndromes (MDS)

- Any International Prognostic Score (IPSS) eligible

- Patients with low or intermediate-1 IPSS must have platelet count <
50,000/mm³ and/or absolute neutrophil count < 500/mm³

- Blast count < 20%

- Chronic myelomonocytic leukemia (dysplastic subtype)

- WBC < 12,000/mm³ (measured twice within the past 4 weeks, 2 weeks apart)

- Acute myeloid leukemia with multilineage dysplasia (AML-TLD)

- Formerly diagnosed refractory anemia with excess blasts in transformation
by FAB criteria allowed

- AML-TLD by WHO criteria allowed in patients with no history of antecedent
hematologic disorder

- WBC ≤ 30,000/mm³ (measured twice within the past 4 weeks, 2 weeks apart)

- WBC that has doubled over 4 weeks AND > 20,000/mm³ is not eligible

- Evidence of ≥ 20% blasts on review of the bone marrow aspirate and/or
biopsy

- SWOG patients must be enrolled in research study trial SWOG-9007

- Therapy-induced MDS, AML-TLD, or chronic myelomonocytic leukemia (dysplastic subtype)
allowed

- No clinical evidence of CNS or pulmonary leukostasis or disseminated intravascular
coagulation

- No clinical evidence of CNS leukemia

- No filgrastim (G-CSF) or pegfilgrastim during days 1-10 of each treatment course

- ECOG performance status 0-2

- Life expectancy ≥ 6 months

- Creatinine < 2.0 mg/dL

- Bilirubin normal (unless due to intramedullary or extramedullary hemolysis, or
Gilbert's syndrome)

- AST and ALT ≤ 2.5 times upper limit of normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No active infections

- No advanced malignant hepatic tumors

- No other serious or uncontrolled medical conditions

- No known hypersensitivity to azacitidine or mannitol

- Recovered from prior therapy

- No prior azacitidine, decitabine or entinostat

- No prior induction chemotherapy for AML or stem cell transplantation

- No hematopoietic growth factors within 3 weeks prior to study entry

- No other concurrent investigational or commercial agents or therapies for the
malignancy

- No concurrent valproic acid, epoetin alfa, or darbepoetin alfa