Inclusion Criteria:

- Histologically confirmed diagnosis of 1 of the following:

- Myelodysplastic syndromes (MDS) meeting the following criteria:

- One of the following types by FAB classification:

- Refractory anemia (RA)

- RA with ringed sideroblasts (RARS)

- RA with excess blasts (RAEB)

- RAEB in transformation

- Chronic myelomonocytic leukemia

- Classified according to International Prognostic Scoring System (IPSS)
criteria as intermediate-1, intermediate-2, or high-risk disease

- Patients with RA or RARS and IPSS ≤ 0.5 or low-risk MDS (IPSS < 0.5) must
meet ≥ 1 of the following criteria:

- Symptomatic anemia requiring packed red blood cell transfusions for ≥
3 months prior to study entry

- Thrombocytopenia with platelet count ≤ 50,000/mm³ or significant
clinical hemorrhage (e.g., gastrointestinal, genitourinary, or
gynecologic hemorrhage requiring platelet transfusions; petechiae
alone do not constitute sufficient hemorrhage)

- Neutropenia with absolute neutrophil count < 1,000/mm³ and an
infection requiring antibiotics

- Less than 30% myeloblasts in the bone marrow (phase II)

- No FAB M6 leukemia (phase II)

- Acute myeloid leukemia (AML) meeting the following criteria*:

- De novo AML or AML evolving from MDS associated with intermediate- or
poor-risk cytogenetics and meeting 1 of the following criteria:

- Declined standard chemotherapy

- Failed or relapsed after 1 prior chemotherapy regimen

- Stable disease, defined as WBC ≤ 25,000/mm³ and no requirement for
hydroxyurea, chemotherapy, or leukapheresis within the past 4 weeks

- MDS cannot be due to leukemic relapse

- No advanced hepatic tumors

- No CNS involvement

- No history of leukemia (phase II)

- Life expectancy > 2 months

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- AST and ALT ≤ 2.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN (unless active hemolysis present or elevation is secondary
to ineffective erythropoiesis)

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- No other malignancy within the past 3 years

- No history of allergic reaction to compounds of similar chemical or biologic
composition to vorinostat (SAHA) or other drugs used in this study

- No uncontrolled concurrent illness, including, but not limited to, the following:

- Symptomatic congestive heart failure (CHF) except high-output CHF secondary to
anemia

- Unstable angina pectoris

- Clinically significant cardiac arrhythmia

- Ongoing or active systemic, bacterial, fungal, or viral infection (must be
afebrile for more than 7 days prior to study entry)

- Psychiatric illness or social situation that would preclude study participation

- No HIV positivity

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- No other concurrent anticancer agents or therapies

- More than 1 month since prior corticosteroids

- More than 1 month since prior interferon

- More than 1 month since prior retinoids

- More than 1 month since prior hematopoietic growth factors, including any of the
following:

- Filgrastim (G-CSF)

- Sargramostim (GM-CSF)

- Epoetin alfa

- At least 2 weeks since prior histone deacetylase inhibitor (e.g., valproic acid)

- More than 4 weeks since prior investigational agent and recovered

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
or radiotherapy for this cancer and recovered

- More than 12 months since prior radiotherapy for another cancer and recovered

- More than 12 months since prior chemotherapy for another cancer and recovered

- No prior antimetabolites, including the following:

- Azacitidine

- Decitabine

- Vorinostat (SAHA)

- No other concurrent investigational agents