Inclusion Criteria:

- Histologically confirmed acute myeloid leukemia (AML) defined by the WHO
classification

- Initial diagnosis with either of the following:

- Bone marrow or peripheral blood myeloblasts of at least 20%,

- Recurring genetic abnormalities (e.g., t[8;21], inv 16, or t[16;16]) and

- Bone marrow blast percentage less than 20%

- Relapsed or refractory disease defined by 1 of the following:

- Under 60 years of age and in second relapse or greater,

- Over 60 years of age and in first relapse,

- Acute promyelocytic leukemia that has relapsed despite prior tretinoin and
arsenic therapy,

- Primary refractory AML for which no standard therapy exists

- Patients who are over 60 years of age with previously untreated disease and who
refuse conventional chemotherapy are eligible

- Patients who are over 60 years of age and in first relapse and poor medical
candidates for reinduction chemotherapy or who refuse conventional chemotherapy are
eligible

- Not medically appropriate for OR refused curative bone marrow or stem cell
transplantation

- No CNS leukemia

- ECOG 0-2 OR Karnofsky 60-100%

- LVEF at least 40% by MUGA

- QTc interval less than 500 msec by EKG

- No myocardial infarction within the past 3 months

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior allergic reactions attributed to compounds of similar chemical or biological
composition to FR901228 (depsipeptide)

- No concurrent uncontrolled illness

- No psychiatric illness or social situation that would preclude study compliance

- No ongoing or active infection

- At least 4 weeks since prior autologous stem cell or bone marrow transplantation

- No prior allogeneic stem cell or bone marrow transplantation

- No concurrent biologic agents

- At least 2 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas)

- No concurrent chemotherapy, concurrent hydroxyurea allowed during the first course of
study therapy to control hyperleukocytosis

- No concurrent radiotherapy

- Recovered from prior therapy

- At least 4 weeks since prior investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational agents

- No concurrent drugs known to have histone deacetylase inhibitor activity (e.g.,
sodium valproate)

- No other concurrent antineoplastic agents

- No prior FR901228 (depsipeptide)

- At least 2 weeks since prior radiotherapy