Busulfan in Treating Children and Adolescents With Refractory CNS Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:
NCT00006246
First received: September 11, 2000
Last updated: October 6, 2009
Last verified: October 2009

September 11, 2000
October 6, 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 [ Designated as safety issue: Yes ]
  • Maximum tolerated dose of IT administered busulfan [ Designated as safety issue: Yes ]
  • Serum and CSF pharmacokinetics of IT administered busulfan [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00006246 on ClinicalTrials.gov Archive Site
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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.

OBJECTIVES:

  • 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.

Interventional
Phase 1
Endpoint Classification: Safety Study
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 ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
28
Not Provided
May 2003   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • 3 to 21

Performance status:

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

Life expectancy:

  • Greater than 8 weeks

Hematopoietic:

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

Hepatic:

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

Renal:

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

Cardiovascular:

  • No cardiac disease

Pulmonary:

  • No pulmonary disease

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • 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

Radiotherapy:

  • 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

Surgery:

  • Not specified

Other:

  • No other concurrent intrathecal or systemic therapy for leptomeningeal disease
Both
3 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00006246
CDR0000068178, PBTC-004
Yes
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