TRIAL OF 17-AAG AND CYTARABINE IN LEUKEMIA AND MYELODSPLASTIC SYNDROME

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Tumor Types: AML: Any non-FAB M3 (APL) AML by WHO diagnostic criteria must fall into 1 of the categories below Failure to achieve a CR with initial induction regimen First relapse within one year of initial CR Failure of re-induction therapy at first or second relapse Second or third relapse in a patient who has received no more than three different induction regimens Antecedent hematologic disorder (MDS, chronic myeloproliferative disease, chronic myelo-monocytic leukemia) Prior chemotherapy for a non-hematologic malignancy High risk cytogenetic abnormalities (abnormalities of chromosome 5,7,8, or 11, or = 3 karyotypic abnormalities) ALL: Any ALL falling into one of the categories below Failure to achieve a CR with initial induction regimen First relapse within one year of initial CR Failure of re-induction therapy at first or second relapse Second or third relapse in a patient who has received no more than three different induction regimens CML: Patients must have an increase in blast percentage in the bone marrow (>10%, i.e. either accelerated or "blast phase") and have failed imatinib mesylate. Patients may have had only one additional treatment regimen in addition to imatinib for their CML. CMML: Patients must have both an increase in blast percentage (>10 %, i.e. CMML 2) as well as evidence of organ infiltration or impending marrow failure as manifested by cytopenias. Additionally patients should not have a t(5;12) by cytogenetics unless they have failed a trial of imatinib mesylate. MDS: High grade MDS patients (defined as >10% blasts on marrow cellularity (RAEB-2) or IPSS MDS prognostic score of >1.5) Performance Status: ECOG Performance Status (PS) 0, 1, or 2. Abnormal Organ Function Permitted: The following laboratory values obtained =7 days prior to registration: Direct bilirubin =1.5 x upper limit of normal (ULN) (unless attributable to underlying disease) Calculated creatinine clearance =60 mL/min Treatment Plan: Cytarabine 400 mg/m2/day continuous infusion days 1 through 5 17-AAG intravenously over 60 minutes on days 3 and 6 Repeat 30 ¿ 5 days after marrow recovery or hospital discharge From previous cycle