OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) of FR901228 (depsipeptide) in pediatric patients with refractory or recurrent solid tumors.
• Determine the dose-limiting toxic effects of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Assess tolerability of this drug at the solid tumor MTD in patients with refractory or recurrent leukemia.
• Determine, preliminarily, the antitumor activity of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients with solid tumors receive escalating doses of FR901228 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Cohorts of 3 patients (6 patients total) with leukemia receive FR901228 as above at the MTD.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 3-30 patients (3-24 with solid tumors and up to 6 with leukemia) will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• 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 NOTE: *Histology requirement waived for patients with brain stem or optic pathway tumors
• 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

PATIENT CHARACTERISTICS:

Age

• Under 22

Performance status

• Karnofsky 60-100% (over 10 years old)
• Lansky 60-100% (10 years old and under)

Life expectancy

• At least 8 weeks

Hematopoietic

• 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)

Hepatic

• 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

Renal

• Glomerular filtration rate at least 70 mL/min OR

• 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)

Cardiovascular

• 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

Pulmonary

• No evidence of dyspnea at rest
• No exercise intolerance
• Pulse oximetry greater than 94%

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• 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

Chemotherapy

• At least 3 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered
• No prior FR901228 (depsipeptide)
• No other concurrent anticancer chemotherapy

Endocrine therapy

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

Radiotherapy

• 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

Surgery

• Not specified

Other

• 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