A PHASE I STUDY OF DEPSIPEPTIDE (NSC#630176, IND# 51810) IN PEDIATRIC PATIENTS WITH REFRACTORY SOLID TUMORS AND LEUKEMIAS

Inclusion Criteria:

- Histologically confirmed malignancy

- Extracranial solid tumors or brain tumors*

- Diagnosis of leukemia allowed after maximum tolerated dose is determined,
including any of the following:

- Acute lymphoblastic leukemia

- Acute myelogenous leukemia

- Chronic myelogenous leukemia in blast crisis

- Disease must be refractory to conventional therapy or no effective conventional
therapy exists

- CNS tumors resulting in neurological deficits must be stable for 2 weeks before study
entry

- Performance status - Karnofsky 60-100% (over 10 years old)

- Performance status - Lansky 60-100% (10 years old and under)

- At least 8 weeks

- Absolute neutrophil count at least 1,000/mm^3 (for solid tumor patients without bone
marrow involvement)

- Platelet count at least 100,000/mm^3 (for solid tumor patients without bone marrow
involvement; platelet transfusion independent) OR 20,000/mm^3 (for leukemia patients;
platelet transfusion allowed)

- Hemoglobin at least 8.0 g/dL (RBC transfusions allowed)

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- ALT no greater than 5 times ULN

- Albumin at least 2 g/dL

- Glomerular filtration rate at least 70 mL/min

- Creatinine based on age as follows:

- No greater than 0.8 mg/dL (for patients 5 years of age and under)

- No greater than 1.0 mg/dL (for patients 6 to 10 years of age)

- No greater than 1.2 mg/dL (for patients 11 to 15 years of age)

- No greater than 1.5 mg/dL (for patients over 15 years of age)

- Calcium normal (with or without supplementation)

- Shortening fraction at least 27% by echocardiogram OR ejection fraction at least 50%
by MUGA

- No symptomatic congestive heart failure

- No uncontrolled cardiac arrhythmia

- QTc less than 450 msec

- No evidence of dyspnea at rest

- No exercise intolerance

- Pulse oximetry greater than 94%

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 1 month after
completion of study treatment

- Magnesium and potassium normal (with or without supplementation)

- No uncontrolled seizure disorder

- No uncontrolled infection

- No graft-vs-host disease

- No seizure disorder unless well controlled and not on enzyme-inducing anticonvulsants

- At least 1 week since prior growth factors

- At least 3 weeks since prior biologic therapy or immunotherapy and recovered

- At least 6 months since prior allogeneic stem cell transplantation

- No concurrent routine prophylactic growth factors

- At least 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)
and recovered

- No prior FR901228 (depsipeptide)

- No other concurrent anticancer chemotherapy

- Concurrent dexamethasone for CNS tumors allowed if on stable dose or decreasing dose
for at least 1 week before study entry

- Recovered from prior radiotherapy

- At least 2 weeks since prior local palliative radiotherapy (small port)

- At least 6 months since prior craniospinal radiotherapy or radiotherapy to at least
50% of pelvis

- At least 6 weeks since other prior substantial bone marrow radiation

- More than a 5 half-life washout period since prior and no concurrent medications
associated with prolongation of QTc interval

- No concurrent enzyme-inducing anticonvulsants

- No concurrent hydrochlorothiazide

- No other concurrent investigational drugs