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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00053963
First received: February 5, 2003
Last updated: January 15, 2013
Last verified: January 2013
  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. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die


Condition Intervention Phase
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
Drug: romidepsin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: 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):

Primary Outcome Measures:
  • MTD, defined as that dose at which fewer than one-third of patients experience DLT, graded according to the NCI CTC version 2.0 [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: September 2002
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Drug: romidepsin
Given IV
Other Names:
  • FK228
  • FR901228
  • Istodax

Detailed Description:

PRIMARY OBJECTIVES:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Maryam Fouladi Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00053963     History of Changes
Obsolete Identifiers: NCT00069771
Other Study ID Numbers: NCI-2012-01803, ADVL0212, U01CA097452, CDR0000269671
Study First Received: February 5, 2003
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
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
Neoplasms, Neuroepithelial
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes
Myeloproliferative Disorders

ClinicalTrials.gov processed this record on September 14, 2014