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Busulfan in Treating Children and Adolescents With Refractory CNS Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00006246
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : October 7, 2009
National Cancer Institute (NCI)
Information provided by:
Pediatric Brain Tumor Consortium

Brief Summary:

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

PURPOSE: Phase I trial to study the safety of delivering intrathecal busulfan in children and adolescents who have refractory CNS cancer and to estimate the maximum tolerated dose of this treatment regimen.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Childhood Germ Cell Tumor Leukemia Lymphoma Metastatic Cancer Retinoblastoma Sarcoma Drug: busulfan Phase 1

Detailed Description:


  • Determine the qualitative and quantitative toxicities of intrathecally administered busulfan in children and adolescents with refractory CNS malignancies.
  • Determine the maximum tolerated dose of this treatment regimen in these patients.
  • Determine the cerebrospinal fluid and serum pharmacokinetics of this treatment regimen in these patients.
  • Determine the efficacy of this treatment regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive intrathecal busulfan twice a week, at least 3 days apart, for 2 weeks. Patients with complete or partial response or stable disease may continue therapy once a week for 2 weeks, once a week every other week for 2 treatments, and then once a month thereafter in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of busulfan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.

Patients are followed every 3 months for the first year, every 6 months for 4 years, and then annually for 5 years.

PROJECTED ACCRUAL: Approximately 18-24 patients will be accrued for this study over 18-38 months.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Primary Purpose: Treatment
Official Title: Phase I Study of Intrathecal Spartaject-Busulfan in Children With Neoplastic Meningitis
Study Start Date : November 2000
Actual Primary Completion Date : May 2003

Primary Outcome Measures :
  1. Toxicities of IT administered busulfan in children and adolescents with refractory CNS malignancies
  2. Maximum tolerated dose of IT administered busulfan
  3. Serum and CSF pharmacokinetics of IT administered busulfan

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed CNS malignancy, including any of the following:

    • Primary malignant brain tumor refractory to standard therapy and metastatic to the cerebrospinal fluid (CSF) or leptomeningeal subarachnoid space
    • Recurrent or persistent leptomeningeal leukemia, lymphoma, or germ cell tumor refractory to conventional therapy

      • In second or greater relapse
      • CSF white blood count greater than 5 cells/mm3 with blasts on cytospin OR
      • Evidence of leptomeningeal tumor by MRI
  • No concurrent bone marrow disease
  • No obstruction or compartmentalization of CSF flow on CSF flow study



  • 3 to 21

Performance status:

  • Lansky 50-100% (under 10 years)
  • Karnofsky 50-100% (10 to 21 years)

Life expectancy:

  • Greater than 8 weeks


  • Absolute neutrophil count greater than 1,000/mm^3
  • Platelet count greater than 75,000/mm^3


  • Bilirubin normal for age
  • ALT and AST less than 5 times upper limit of normal (ULN)
  • No hepatic disease


  • Creatinine no greater than 1.5 times ULN OR
  • Glomerular filtration rate greater than 70 mL/min
  • No renal disease


  • No cardiac disease


  • No pulmonary disease


  • No uncontrolled infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception


Biologic therapy:

  • Not specified


  • At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
  • At least 1 week since prior intrathecal chemotherapy (2 weeks for cytarabine) and recovered
  • Evidence of subsequent disease progression
  • Concurrent systemic chemotherapy allowed for recurrent disease after first course of treatment except for the following:

    • Chemotherapy targeted at leptomeningeal disease
    • Other phase I agent
    • Any agent that significantly penetrates the CSF (e.g., high dose methotrexate greater than 1 g/m2, thiotepa, high dose cytarabine, fluorouracil, IV mercaptopurine, nitrosoureas, or topotecan)
    • Any agent that causes serious unpredictable CNS side effects

Endocrine therapy:

  • Prior dexamethasone allowed with decreasing or stable dose at least one week before study
  • Concurrent dexamethasone or prednisone with chemotherapy regimen allowed


  • At least 1 week since prior focal irradiation to the brain or spine
  • At least 8 weeks since prior craniospinal irradiation
  • No concurrent cranial or craniospinal irradiation


  • Not specified


  • No other concurrent intrathecal or systemic therapy for leptomeningeal disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00006246

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United States, California
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, United States, 94143-0128
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
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Study Chair: Sri Gururangan, MD Duke University

Publications of Results:
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Responsible Party: James M. Boyett/PBTC Operations and Biostatistics Center Executive Director, Pediatric Brain Tumor Consortium Identifier: NCT00006246     History of Changes
Other Study ID Numbers: CDR0000068178
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: October 7, 2009
Last Verified: October 2009
Keywords provided by Pediatric Brain Tumor Consortium:
recurrent childhood acute lymphoblastic leukemia
childhood infratentorial ependymoma
recurrent childhood rhabdomyosarcoma
recurrent childhood brain tumor
recurrent retinoblastoma
recurrent childhood lymphoblastic lymphoma
childhood central nervous system germ cell tumor
recurrent childhood acute myeloid leukemia
recurrent/refractory childhood Hodgkin lymphoma
leptomeningeal metastases
childhood high-grade cerebral astrocytoma
childhood oligodendroglioma
childhood choroid plexus tumor
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
recurrent childhood large cell lymphoma
recurrent childhood brain stem glioma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
recurrent childhood medulloblastoma
recurrent childhood visual pathway and hypothalamic glioma
recurrent childhood ependymoma
recurrent childhood malignant germ cell tumor
Additional relevant MeSH terms:
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Neoplasms, Germ Cell and Embryonal
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Retinal Neoplasms
Eye Neoplasms
Eye Diseases, Hereditary
Eye Diseases
Retinal Diseases
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating