Phase I Study of Intrathecal Spartaject-Busulfan in Children With Neoplastic Meningitis

Inclusion 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