A Nonrandomized Dose-escalation Study of Clofarabine in Combination With Gemtuzumab Ozogamicin for Relapsed/Refractory Acute Myeloid Leukemia (AML) for Patients Less Than 60 Years-old

Date de début de l'étude : 1 novembre 2007

DISEASE CHARACTERISTICS: * Diagnosis of acute myeloid leukemia (AML) meeting 1 of the following criteria: * Refractory disease, defined as persistent or progressive disease after ≥ 2 induction regimens, including ≥ 1 course of high-dose cytarabine (ARA-C) * Relapsed disease that has recurred within 1 year of an ARA-C-containing chemotherapy regimen * No CNS disease requiring radiotherapy * Patients with neurological symptoms must undergo a lumbar puncture and a CT scan or MRI of the brain to exclude brain metastasis PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Total bilirubin ≤ 2.0 times upper limit of normal (ULN) * ALT and AST ≤ 2.0 times the ULN * Serum creatinine ≤ 1.0 mg/dL OR glomerular filtration rate \> 60 mL/min * INR ≤ 1.5 and aPTT within ULN * Patients receiving anticoagulation therapy (e.g., warfarin or heparin) are eligible provided anticoagulation therapy can be discontinued or changed to parenteral medications while the platelet count is less than 50,000/mm³ * Negative pregnancy test * Fertile patients must use effective contraception * No concurrent active second primary malignancy (excluding superficial, non-invasive skin cancers) * No active bleeding diathesis, not including closely monitored therapeutic anticoagulation * No cardiac disease, including any of the following: * New York Heart Association class II-IV congestive heart failure * Unstable angina (i.e., anginal symptoms at rest) * New onset angina (i.e., began within the past 3 months) * Myocardial infarction within the past 6 months * No active clinically serious infection \> grade 2 * No cerebrovascular accident, including transient ischemic attacks, within the past 6 months * No pulmonary hemorrhage ≥ grade 2 within the past 4 weeks * No other hemorrhage or bleeding event ≥ grade 3 within the past 4 weeks * No known HIV infection or chronic hepatitis B or C * No serious non-healing wound or ulcer * More than 4 weeks since prior significant traumatic injury * No prior history of sinusoidal obstructive syndrome (veno-occlusive disease) PRIOR CONCURRENT THERAPY: * More than 4 weeks since prior major surgery or open biopsy * More than 100 days since any prior hematopoietic stem cell transplant * No concurrent treatment with any other investigational agent for AML * Intrathecal chemotherapy administration is allow for central nervous system leukemic infiltration * No prior allogeneic stem cell transplant within the past 100 days, with active graft-versus-host disease (GVHD) of any grade, or exposure to immynosuppression for GVHD or prophylaxis