• Therapeutic activity [ Designated as safety issue: No ]
• Safety and toxicity [ Designated as safety issue: Yes ]
• Concentration of matrix metalloproteinases in the CSF [ Designated as safety issue: No ]

• Objective response rate (leukemia and lymphoma patients)
• Event-free patients (solid tumors patients)
• Event-free patients at 6 months (medulloblastoma patients)

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well topotecan works in treating children with meningeal cancer that has not responded to previous treatment.

OBJECTIVES:

• Determine the therapeutic activity of intrathecal topotecan, in terms of response rate and time to CNS progression, in pediatric patients with recurrent or refractory neoplastic meningitis.
• Determine the safety and toxicity of this regimen in these patients.
• Evaluate the concentration of matrix metalloproteinases (MMPs) in the CSF of these patients.

OUTLINE: Patients are stratified according to disease type (acute lymphoblastic leukemia vs other leukemia/lymphoma vs medulloblastoma vs other solid tumors). (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04)

• Induction: Patients receive topotecan intrathecally (IT) over 5 minutes twice weekly for 6 weeks.
• Consolidation: Beginning 1 week after completion of induction, patients receive topotecan IT over 5 minutes weekly for 4 weeks in the absence of disease progression or unacceptable toxicity.
• Maintenance: Beginning 2 weeks after completion of consolidation, patients receive topotecan IT over 5 minutes twice monthly for 4 months and then monthly through year 1.

Patients are followed monthly for 3 months, every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 14-77 patients will be accrued for this study.

• Brain and Central Nervous System Tumors
• Leukemia
• Lymphoma
• Metastatic Cancer
• Unspecified Childhood Solid Tumor, Protocol Specific

DISEASE CHARACTERISTICS:

• Histologically proven refractory leukemia, lymphoma, or other solid tumor that has 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 on cytospin 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 of meningeal disease on MRI scans

• No clinical evidence of obstructive hydrocephalus or compartmentalization of CSF flow as documented by radioisotope indium In 111 or technetium Tc 99 DTPA flow study

  • If CSF flow block is demonstrated, focal radiotherapy must be administered to site 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 based lesions

PATIENT CHARACTERISTICS:

Age:

• 1 to 21

Performance status:

• Lansky 50-100% (age 10 and under)
• Karnofsky 50-100% (over age 10)

Life expectancy:

• At least 8 weeks

Hematopoietic:

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

Hepatic:

• Bilirubin less than 2.0 mg/dL
• SGPT less than 5 times normal

Renal:

• Creatinine less than 1.5 mg/dL
• Electrolytes, calcium, and phosphorus normal

Other:

• 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 CONCURRENT THERAPY:

Biologic therapy:

• Prior immunotherapy allowed and recovered

Chemotherapy:

• 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

Endocrine therapy:

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

Radiotherapy:

• See Disease Characteristics
• At least 8 weeks since prior cranial irradiation and recovered
• No concurrent whole brain or craniospinal irradiation

Surgery:

• Not specified

Other:

• 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