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.

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