A Pilot Study of Lestaurtinib (CEP-701) in Combination With Chemotherapy in Young Patients With Relapsed or Refractory FLT3-mutant Acute Myeloid Leukemia

Inclusion Criteria

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)