Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

You may be eligible if

• Histologically or cytologically confirmed diagnosis of 1 of the following:
• * Relapsed or refractory acute myeloid leukemia (AML)
• * Patients with acute promyelocytic leukemia t(15;17) must have failed prior tretinoin and arsenic trioxide-containing regimen
• * Must be refractory to both agents with absence of durable hematologic response OR relapsed after a complete response duration of \< 6 months
• * Relapsed or refractory acute lymphoblastic leukemia
• * Chronic myelogenous leukemia in accelerated or blastic phase
• * Must be refractory to treatment with imatinib mesylate or dasatinib
• * Disease progression despite continued treatment with imatinib mesylate or dasatinib
• * AML arising in the setting of underlying myelodysplastic syndromes (MDS) and/or myeloproliferative disorders (MPD)
• * Secondary or therapy-related AML
• No active CNS leukemia
• Leukostasis OR leukemic blast count \> 50,000/mm³ allowed provided patient is treated with emergency leukapheresis or hydroxyurea to reduce leukemic blast count to \< 30,000/mm³
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Creatinine ≤ 2.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of cytarabine-related neurotoxicity
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA) or other agents used in the study
• No other uncontrolled illness, including, but not limited to, any of the following:
• * Symptomatic congestive heart failure
• * Unstable angina pectoris
• * Cardiac arrhythmia
• * Psychiatric illness or social situation that would preclude compliance with study requirements
• Infection allowed provided patient is receiving active treatment
• No HIV positivity
• See Disease Characteristics
• Recovered from prior therapy
• * Persistent alopecia, fingernail discoloration, or hematologic abnormalities (primarily related to underlying disease) \> 4 weeks after last course of chemotherapy or radiotherapy does not exclude patient
• At least 2 weeks since prior valproic acid or any other histone deacetylase inhibitor
• No more than 3 prior courses of induction/reinduction chemotherapy, including induction and consolidation therapy or induction therapy after any bone marrow transplantation or similar procedure
• * Prior low-dose azacitidine, growth factors, cytokines, thalidomide, interferon, or imatinib mesylate for treatment of preceding MDS/MPD do not count as prior induction/reinduction therapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas \[e.g., carmustine\] or mitomycin C) or radiotherapy
• At least 24 hours since prior hydroxyurea
• At least 2 weeks since prior imatinib mesylate, hematopoietic growth factors, and biological agents
• At least 4 weeks since prior autologous stem cell transplantation
• Prior allogeneic stem cell transplantation allowed if all of the following criteria are met:
• * At least 90 days since prior transplant
• * No evidence of graft-vs-host disease
• * At least 2 weeks since prior immunosuppressive therapy
• No other concurrent anticancer agents or therapies
• No other concurrent investigational agents
• Concurrent hydroxyurea or leukapheresis allowed on days 1-10 of study treatment to control rising leukemic blasts (blasts \> 30,000/mm³) or leukostasis