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

September 11, 2000
January 27, 2003
October 7, 2009
November 2000
May 2003   (Final data collection date for primary outcome measure)
  • Toxicities of IT administered busulfan in children and adolescents with refractory CNS malignancies
  • Maximum tolerated dose of IT administered busulfan
  • Serum and CSF pharmacokinetics of IT administered busulfan
Not Provided
Complete list of historical versions of study NCT00006246 on Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
Busulfan in Treating Children and Adolescents With Refractory CNS Cancer
Phase I Study of Intrathecal Spartaject-Busulfan in Children With Neoplastic Meningitis

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.


  • 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.

Phase 1
Primary Purpose: Treatment
  • Brain and Central Nervous System Tumors
  • Childhood Germ Cell Tumor
  • Leukemia
  • Lymphoma
  • Metastatic Cancer
  • Retinoblastoma
  • Sarcoma
Drug: busulfan
Not Provided
Gururangan S, Petros WP, Poussaint TY, Hancock ML, Phillips PC, Friedman HS, Bomgaars L, Blaney SM, Kun LE, Boyett JM. Phase I trial of intrathecal spartaject busulfan in children with neoplastic meningitis: a Pediatric Brain Tumor Consortium Study (PBTC-004). Clin Cancer Res. 2006 Mar 1;12(5):1540-6.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Not Provided
Not Provided
May 2003   (Final data collection date for primary outcome measure)


  • 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
Sexes Eligible for Study: All
3 Years to 21 Years   (Child, Adult)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
James M. Boyett/PBTC Operations and Biostatistics Center Executive Director, Pediatric Brain Tumor Consortium
Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
Study Chair: Sri Gururangan, MD Duke University
Pediatric Brain Tumor Consortium
October 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP