A Phase II Study of Intrathecal Topotecan (NSC #609699) in Patients With Refractory Meningeal Malignancies

Inclusion Criteria:

- Histologically proven refractory leukemia, lymphoma, or other solid tumor thathas
overt meningeal involvement (Recurrent CNS acute lymphoblastic leukemia stratum only
open to accrual as of 11/30/04)

- Definition of meningeal disease:

- Leukemia/lymphoma (including acute lymphoblastic leukemia)

- CSF cell count greater than 5/mm^3 AND evidence of blast cells
oncytospin preparation or by cytology

- Refractory to conventional therapy, including radiotherapy (i.e., in
second or greater relapse)

- No concurrent bone marrow relapse

- Solid tumors (including medulloblastoma)

- Presence of tumor cells on cytospin preparation or cytology OR
presence ofmeningeal disease on MRI scans

- No clinical evidence of obstructive hydrocephalus or compartmentalization ofCSF flow
as documented by radioisotope indium In 111 or technetium Tc 99 DTPAflow study

- If CSF flow block is demonstrated, focal radiotherapy must be administered
tosite of block to restore flow and a repeat CSF flow study must show clearing
of blockage

- No ventriculoperitoneal or ventriculoatrial shunt unless:

- Patient is shunt independent and there is evidence that the shunt is
nonfunctional

- CSF flow study demonstrates normal flow

- No impending cord compression, CNS involvement requiring local radiotherapy(e.g.,
optic nerve), or isolated bulky ventricular or leptomeningeal basedlesions

- Performance status - Lansky 50-100% (age 10 and under)

- Performance status - Karnofsky 50-100% (over age 10)

- At least 8 weeks

- Platelet count greater than 40,000/mm^3 (transfusions allowed)

- Bilirubin less than 2.0 mg/dL

- SGPT less than 5 times normal

- Creatinine less than 1.5 mg/dL

- Electrolytes, calcium, and phosphorus normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No significant illness (e.g., uncontrolled infection, except HIV [i.e., AIDS-related
lymphomatous meningitis])

- Prior immunotherapy allowed and recovered

- At least 3 weeks since systemic CNS directed chemotherapy (6 weeks for nitrosoureas)
and recovered

- At least 1 week since prior intrathecal (IT) chemotherapy (2 weeks for cytarabine
[liposomal])

- No prior IT chemotherapy on days -14 to -7 before study entry unless evidence of
disease progression (e.g., increasing WBC and percentage blasts in patients with
leukemia/lymphoma or increased leptomeningeal enhancements in patients with solid
tumors) (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as
of 11/30/04)

- Concurrent chemotherapy to control systemic disease or bulk CNS disease allowed if
the systemic chemotherapy is not a phase I study agent that significantly penetrates
the CSF (e.g., high-dose systemic methotrexate [greater than 1 g/m^2], thiotepa,
high-dose cytarabine, temozolomide, IV mercaptopurine, nitrosourea, or topotecan) or
an agent known to have serious unpredictable CNS side effects

- Concurrent dexamethasone or prednisone allowed if part of a systemic chemotherapy
regimen

- See Disease Characteristics

- At least 8 weeks since prior cranial irradiation and recovered

- No concurrent whole brain or craniospinal irradiation

- At least 7 days since prior investigational drug

- Time period should be extended if patient has received any investigational
agent that is known to have delayed toxic effects after 7 days or a prolonged
half-life

- No other concurrent investigational agents

- No concurrent therapy (IT or systemic) for leptomeningeal disease

- No other concurrent systemic agents that significantly penetrate the blood-brain
barrier