Busulfan in Treating Children and Adolescents With Refractory CNS Cancer
Condition: Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Leukemia; Lymphoma; Metastatic Cancer; Retinoblastoma; Sarcoma
MeSH terms: Lymphoma; Neoplasms; Leukemia; Neoplasms, Germ Cell and Embryonal; Nervous System Neoplasms; Central Nervous System Neoplasms; Retinoblastoma
Study type: Interventional
Phase: Phase 1

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.
    

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.
    

Intervention name(s): busulfan
Intervention type(s): Drug
Intervention MeSH terms: Busulfan
Primary purpose: Treatment
Keywords: 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