FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia

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