Lestaurtinib, Cytarabine, and Idarubicin in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

DISEASE CHARACTERISTICS:

• Diagnosis of acute myeloid leukemia (AML) according to FAB classification
• At least 5% blasts in the bone marrow, with or without extramedullary disease
• In first relapse after induction therapy OR refractory to induction therapy with ≤ 1 attempt at remission induction
• Patients who are in a first relapse > 1 year from their initial diagnosis of AML are excluded from the dose-finding phase of the study, but are eligible for the efficacy phase
• First relapse after hematopoietic stem cell transplantation (HSCT) allowed provided patient has no evidence of active graft-versus-host disease (GVHD) and is at least 4 months posttransplantation
• Positive for a FLT3 activating mutation (internal tandem duplication or kinase domain point mutation) using standard polymerase chain reaction-based procedures at any time in the course of illness
• Treatment-related AML allowed

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤ 16 years of age)
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum creatinine based on age and gender as follows:
• Creatinine no greater than 0.4 mg/dL (1 month to < 6 months of age)
• Creatinine no greater than 0.5 mg/dL (6 months to < 1 year of age)
• Creatinine no greater than 0.6 mg/dL (1 year to < 2 years of age)
• Creatinine no greater than 0.8 mg/dL (2 years to < 6 years of age)
• Creatinine no greater than 1 mg/dL (6 years to < 10 years of age)
• Creatinine no greater than 1.2 mg/dL (10 years to < 13 years of age)
• Creatinine no greater than 1.4 mg/dL (females) or 1.5 mg/dL (males) (13 years to < 16 years of age)
• Creatinine no greater than 1.4 mg/dL (females) or 1.7 mg/dL (males) (16 years of age and over)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT < 5 times ULN (unless it is related to leukemic involvement)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy
• No prior cumulative anthracycline doses exceeding 450 mg/m^2 daunorubicin equivalents
• Patients who relapse after receiving treatment on protocol COG-AAML03P1 or COG-AAML0531 (300 mg/m^2 of daunorubicin hydrochloride and 48 mg/m^2 of mitoxantrone hydrochloride) allowed provided they have not received any additional anthracyclines
• At least 14 days since prior cytotoxic therapy
• Hydroxyurea allowed to decrease the WBC prior to starting protocol treatment
• No concurrent hydroxyurea
• At least 7 days since prior biologic agents
• At least 14 days since prior monoclonal antibody therapy
• Radiotherapy to chloromas allowed
• Irradiated lesion may not be used to assess tumor response
• No other concurrent chemotherapy, investigational therapy, immunomodulating agents, or steroids
• Steroids used as an antiemetic allowed
• Prophylactic intrathecal cytarabine allowed
• No concurrent CYP3A4, 5 inhibitors, including any of the following:
• Azole antifungals (e.g., fluconazole or voriconazole)
• Cyclosporine
• Erythromycin
• Clarithromycin
• Troleandomycin
• HIV protease inhibitors
• Nefazodone
• No concurrent CYP3A4, 5 inducers, including any of the following:
• Carbamazepine
• Dexamethasone
• Rifampin
• Phenobarbital
• Phenytoin
• Hypericum perforatum (St. John's wort)