Clinical trial NCT00357305 (phase 1, status: completed)
Conditions: accelerated phase chronic myelogenous leukemia, adult acute basophilic leukemia, adult acute eosinophilic leukemia, adult acute megakaryoblastic leukemia (m7), adult acute minimally differentiated myeloid leukemia (m0), adult acute monoblastic leukemia (m5a), adult acute monocytic leukemia (m5b), adult acute myeloblastic leukemia with maturation (m2), adult acute myeloblastic leukemia without maturation (m1), adult acute myeloid leukemia with 11q23 (mll) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myelomonocytic leukemia (m4), adult acute promyelocytic leukemia (m3), adult erythroleukemia (m6a), adult pure erythroid leukemia (m6b), atypical chronic myeloid leukemia, bcr-abl1 negative, blastic phase chronic myelogenous leukemia, chronic eosinophilic leukemia, chronic myelomonocytic leukemia, chronic neutrophilic leukemia, de novo myelodysplastic syndromes, essential thrombocythemia, myelodysplastic/myeloproliferative neoplasm, unclassifiable, polycythemia vera, previously treated myelodysplastic syndromes, primary myelofibrosis, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, secondary myelodysplastic syndromes
ICD codes: C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, J82.83, K20.0, K52.82, I42.3, J82.81, J82.82, L98.3, C94.21, C94.22, C94.20, C7A.1, C93.01, C93.02, C93.00, C93.Z1, C93.Z2, C93.91, C93.92, C93.01, C93.02, C93.Z0, C92.01, C92.02, C92.00, C92.01, C92.02, C92.00, R19.5, H35.09, M26.50, M26.59, Q99.8, R06.89, R06.9, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, C92.51, C92.52, C93.11, C93.12, C93.31, C93.32, C92.50, C94.01, C94.02, C94.00, G50.1, I48.4, H57.01, M84.750S, N42.32, M84.751S, M84.752S, C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, J82.83, K20.0, K52.82, I42.3, J82.81, J82.82, L98.3, C93.11, C93.12, C93.10, L98.2, D46.Z, D46.9, C94.6, D46.C, D47.3, C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2, D45, D46.Z, D46.9, C94.6, D46.C, D75.81, C94.41, C94.42, C94.40, C83.57, C83.50, C91.01, C91.02, C83.52, C83.56, C83.53, G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2, M94.1, A68.9, A68.0, A68.1, M35.6, D75.1, E26.1, N91.1, N91.4, N94.5, A51.41, A51.43, D46.Z, D46.9, C94.6, D46.C
Drugs: vorinostat, cytarabine, etoposide
SMILES: ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1, ClCCN(CCCl)P1(=O)NCCCO1, OCCOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1
Eligibility criteria:

        Inclusion Criteria:

          -  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

                    -  Patients in accelerated or blastic phase are eligible if unable to tolerate
                       imatinib mesylate provided their disease has progressed on dasatinib or if
                       unable to tolerate 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