Topotecan Hydrochloride in Treating Children With Meningeal Cancer That Has Not Responded to Previous Treatment

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