A PHASE I COOPERATIVE AGREEMENT PEDIATRIC TRIAL OF MITOXANTRONE, ETOPOSIDE AND PSC-833 (PSC-ME) THERAPY IN PATIENTS WITH RELAPSED AND REFRACTORY ACUTE LEUKEMIA

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Acute myeloid leukemia (AML) in one of the following categories:

- First relapse if initial CR less than 6 months

- Refractory to first or second induction with daunomycin, cytarabine, and thioguanine
(DAT) or other anthracycline-containing regimens

- Relapse following bone marrow transplantation provided good trilineage engraftment
followed transplant and greater than 6 months since transplant

- Presentation with secondary AML or AML evolving from myelodysplastic syndrome --Acute
lymphocytic leukemia in one of the following categories:

- In second or subsequent relapse or failed second or later induction attempts
regardless of prior remissions

- Relapsed following bone marrow transplantation provided good trilineage engraftment
followed transplant and greater than 6 months since transplant

- No isolated CNS or extramedullary relapse

PATIENT CHARACTERISTICS:

- Age: Under 22 at diagnosis

- Performance status: Karnofsky 50-100% (ECOG 0-2)

- Lansky 40-100% (in patients under 12 years of age)

- Life expectancy: At least 8 weeks

- Bilirubin less than 1.5 mg/dL

- ALT less than twice normal

- Creatinine normal for age (within 2 standard deviations) OR glomular filtration rate
at least 70 mL/min

- Albumin at least 3 g/dL

- Ejection fraction greater than 50% at rest or with 5% increase with exercise OR
shortening fraction greater than 27% by echocardiogram

- No history of clinical heart failure

- No uncontrolled infection

- No anticonvulsant therapy

- No history of allergic reactions or anaphylaxis to etoposide not remediable by
premedication

- Not pregnant or nursing

- Fertile patients must use effective contraception

- Third percentile weight for height

PRIOR CONCURRENT THERAPY:

- At least 4 weeks since chemotherapy and recovered

- Prior cumulative anthracycline dose no greater than 360 mg per square meter

- Hydroxyurea therapy allowed just prior to study for rapidly rising blast count