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)