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Phase 1
21 Years
Not Enrolling
Blastic Phase Chronic Myelogenous Leukemia, Childhood Central Nervous System Germ Cell Tumor, Childhood Choroid Plexus Tumor, Childhood Chronic Myelogenous Leukemia, Childhood Craniopharyngioma, Childhood Grade I Meningioma, Childhood Grade II Meningioma, Childhood Grade III Meningioma, Childhood High-grade Cerebral Astrocytoma, Childhood Infratentorial Ependymoma, Childhood Low-grade Cerebral Astrocytoma, Childhood Spinal Cord Neoplasm, Childhood Supratentorial Ependymoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Childhood Brain Stem Glioma, Recurrent Childhood Cerebellar Astrocytoma, Recurrent Childhood Cerebral Astrocytoma, Recurrent Childhood Ependymoma, Recurrent Childhood Medulloblastoma, Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor, Recurrent Childhood Visual Pathway and Hypothalamic Glioma, Refractory Chronic Lymphocytic Leukemia, Relapsing Chronic Myelogenous Leukemia, Unspecified Childhood Solid Tumor, Protocol Specific

Thank you

Trial Information



I. Determine the maximum tolerated dose (MTD) of FR901228 (depsipeptide) in pediatric
patients with refractory or recurrent solid tumors.

II. Determine the dose-limiting toxic effects of this drug in these patients. III. Determine
the pharmacokinetics of this drug in these patients. IV. Assess tolerability of this drug at
the solid tumor MTD in patients with refractory or recurrent leukemia.

V. 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.

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

- 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%

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD, defined as that dose at which fewer than one-third of patients experience DLT, graded according to the NCI CTC version 2.0

Outcome Time Frame:

Up to 28 days

Safety Issue:


Principal Investigator

Maryam Fouladi

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

September 2002

Completion Date:

Related Keywords:

  • Blastic Phase Chronic Myelogenous Leukemia
  • Childhood Central Nervous System Germ Cell Tumor
  • Childhood Choroid Plexus Tumor
  • Childhood Chronic Myelogenous Leukemia
  • Childhood Craniopharyngioma
  • Childhood Grade I Meningioma
  • Childhood Grade II Meningioma
  • Childhood Grade III Meningioma
  • Childhood High-grade Cerebral Astrocytoma
  • Childhood Infratentorial Ependymoma
  • Childhood Low-grade Cerebral Astrocytoma
  • Childhood Spinal Cord Neoplasm
  • Childhood Supratentorial Ependymoma
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Recurrent Childhood Brain Stem Glioma
  • Recurrent Childhood Cerebellar Astrocytoma
  • Recurrent Childhood Cerebral Astrocytoma
  • Recurrent Childhood Ependymoma
  • Recurrent Childhood Medulloblastoma
  • Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
  • Recurrent Childhood Visual Pathway and Hypothalamic Glioma
  • Refractory Chronic Lymphocytic Leukemia
  • Relapsing Chronic Myelogenous Leukemia
  • Unspecified Childhood Solid Tumor, Protocol Specific
  • Astrocytoma
  • Blast Crisis
  • Neoplasms
  • Craniopharyngioma
  • Adamantinoma
  • Ependymoma
  • Glioma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Medulloblastoma
  • Meningioma
  • Spinal Cord Neoplasms
  • Choroid Plexus Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Optic Nerve Glioma



Children's Oncology Group Arcadia, California  91006-3776