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
  Purpose

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: Phase I Study of Intrathecal Spartaject-Busulfan in Children With Neoplastic Meningitis

Resource links provided by NLM:


Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:
  • 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 ]

Enrollment: 28
Study Start Date: November 2000
Primary Completion Date: May 2003 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00006246

Locations
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
Investigators
Study Chair: Sri Gururangan, MD Duke University
  More Information

Additional Information:
Publications:
Responsible Party: James M. Boyett/PBTC Operations and Biostatistics Center Executive Director, Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT00006246     History of Changes
Other Study ID Numbers: CDR0000068178, PBTC-004
Study First Received: September 11, 2000
Last Updated: October 6, 2009
Health Authority: United States: Food and Drug Administration

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:
Lymphoma
Leukemia
Neoplasms
Neoplasm Metastasis
Nervous System Neoplasms
Central Nervous System Neoplasms
Retinoblastoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes
Neoplasms by Site
Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Retinal Neoplasms
Eye Neoplasms
Eye Diseases
Retinal Diseases
Busulfan
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 16, 2014