Clinical Trial Finder

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

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.