INCLUSION CRITERIA:
IMPORTANT NOTE: The eligibility criteria listed below are interpreted literally and cannot be waived.
Planned start of treatment must be within 7 days of fulfilling all eligibility criteria, unless otherwise specified.
Patient must be less than 22 years of age at the time of study entry.
Patients with solid tumors, either extracranial solid tumors or brain tumors, are eligible. Patients must have had histologic verification of the diagnosis of malignancy at the time of initial diagnosis, with the exception of patients with brain stem or optic pathway tumors, for whom the requirement for histologic verification is waived. Patients with recurrent or refractory leukemia will not be eligible for the dose escalation part of the study. Once an MTD is reached, however, 6 patients with recurrent or refractory leukemia, in cohorts of 3, will be enrolled at the solid tumor MTD to assess tolerability in patients with leukemia.
Patient's disease must be considered refractory to conventional therapy, or no effective conventional therapy must exit.
Karnofsky greater than or equal to 60% for patients greater 10 years of age and Lansky greater than or equal to 60 for children less than or equal to 10 years of age. Neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 2 weeks prior to study entry. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
Life expectancy must be greater than or equal to 8 weeks.
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
Myelosuppressive chemotherapy and biologic: Must not have received within 3 weeks of entry onto this study (4 weeks if prior nitrosourea).
XRT: greater than or equal to 2 weeks for local palliative XRT (small port); greater than or equal to 6 months must have elapsed if prior craniospinal XRT or if greater than or equal to 50% radiation of pelvis; greater than or equal to 6 weeks must have elapsed if other substantial BM radiation.
Stem Cell Transplant (SCT): No evidence of active graft vs. host disease. For allogeneic SCT, greater than or equal to 6 months must have elapsed.
Patients must show evidence of full recovery from acute toxic effects of all prior chemotherapy or radiotherapy prior to study entry.
Concomitant Medications
Growth factor(s): Must not have received within 1 week of entry onto this study.
Steroids: Patients with CNS tumors who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to study entry.
Anticonvulsants: Must not be receiving enzyme-inducing anticonvulsant drugs.
Patients cannot be on medications associated with prolongation of QTc interval. Depsipeptide may be administered after a 5 half-life washout period elapses following the use of these drugs.
Organ Function Requirements
Adequate Bone Marrow Function Defined As: For all patients including those post SCT:
Peripheral absolute neutrophil count (ANC) greater than or equal to 1000/microL
Platelet count greater than or equal to 100,000/microL (transfusion independent)
Hemoglobin greater than or equal to 8.0 gm/dL (may receive RBC transfusions)
Adequate Renal Function Defined As:
An age-adjusted normal serum creatinine:
Less than or equal to 5 years---Maximum Serum Creatinine 0.8 mg/dL
Greater than 5 and less than or equal to 10 yrs---Maximum Serum Creatinine 1.0 mg/dL
Greater than 10 and less than or equal to 15 yrs---Maximum Serum Creatinine 1.2 mg/dL
Greater than 15 years---Maximum Serum Creatinine 1.5 mg/dL
OR
A GFR greater than or equal to 70 ml/min/1.73m(2).
Adequate Liver Function Defined As:
Total bilirubin less than or equal to 1.5 X institutional upper limit of normal for age,
SGPT (ALT) less than or equal to 5 X institutional upper limit of normal for age, and
Albumin greater than or equal to 2 g/dL.
Adequate Cardiac Function Defined As:
Shortening fraction of greater than or equal to 27% by echocardiogram, or
Ejection fraction of greater than or equal to 50% by gated radionuclide study.
Adequate Pulmonary Function Defined As:
No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry greater than 94% if there is clinical indication for determination.
Central Nervous System Function Defined As:
Patients with seizure disorder may be enrolled if well controlled and not on enzyme-inducing anti-convulsants.
Adequate serum calcium, magnesium and potassium concentrations
Serum total calcium (or ionized calcium if hypoalbuminemia), magnesium and potassium must exceed the institutional lower limit of normal for age (with or without supplementation).
EXCLUSION CRITERIA:
There is no available information regarding human fetal or teratogenic toxicities of depsipeptide. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. Lactating women must agree not to breast-feed.
Patients who have an uncontrolled infection.
Patients with leukemia will be excluded from the dose escalation component of the trial. However, once the dose finding component of the trial is completed, and the MTD is established in patients with refractory or recurrent solid tumor, 6 patients with relapsed or refractory leukemia will be enrolled at the MTD to assess tolerability.
Patients who have previously received depsipeptide.
Patients with symptoms of congestive heart failure, uncontrolled cardiac rhythm disturbance, or a QTC that is greater than or equal to 450 msec.
All patients and/or their parents or legal guardians must sign a written informed consent.
All institutional, FDA, and NCI requirements for human studies must be met.
Warren Grant Magnuson Clinical Center (CC)