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FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia
This study has been completed.
First Received: February 5, 2003   Last Updated: August 23, 2008   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00053963
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of FR901228 in treating children with refractory or recurrent solid tumors or leukemia.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Leukemia
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: romidepsin
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study of Depsipeptide (NSC#630176, IND#51810) in Pediatric Patients With Refractory Solid Tumors and Leukemias

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: December 2002
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00053963

Locations
United States, California
Stanford Cancer Center at Stanford University Medical Center
Palo Alto, California, United States
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States
United States, Maryland
NCI - Pediatric Oncology Branch
Bethesda, Maryland, United States
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States
United States, Minnesota
Fairview University Medical Center - University Campus
Minneapolis, Minnesota, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, United States
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States
SUNY Upstate Medical University Hospital
Syracuse, New York, United States
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
United States, Oregon
Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
United States, Texas
Baylor University Medical Center - Houston
Houston, Texas, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Maryam Fouladi, MD Children's Hospital Medical Center, Cincinnati
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000269671, COG-ADVL0212, NCI-03-C-0307
Study First Received: February 5, 2003
Last Updated: August 23, 2008
ClinicalTrials.gov Identifier: NCT00053963     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
unspecified childhood solid tumor, protocol specific
recurrent childhood acute lymphoblastic leukemia
blastic phase chronic myelogenous leukemia
recurrent childhood acute myeloid leukemia
refractory chronic lymphocytic leukemia
relapsing chronic myelogenous leukemia
childhood chronic myelogenous leukemia
childhood central nervous system germ cell tumor
childhood choroid plexus tumor
childhood craniopharyngioma
childhood infratentorial ependymoma
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
childhood spinal cord neoplasm
childhood supratentorial ependymoma
recurrent childhood brain stem glioma
recurrent childhood cerebellar astrocytoma
recurrent childhood ependymoma
childhood high-grade cerebral astrocytoma
childhood low-grade cerebral astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood medulloblastoma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway and hypothalamic glioma

Additional relevant MeSH terms:
Leukemia
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Antineoplastic Agents
Therapeutic Uses
Nervous System Diseases
Romidepsin
Central Nervous System Neoplasms
Antibiotics, Antineoplastic
Pharmacologic Actions
Nervous System Neoplasms

ClinicalTrials.gov processed this record on November 09, 2009