Phase 1 Intrathecal Topotecan for Neoplastic Meningitis

Inclusion Criteria: 1. Age: Patients must be greater than or equal to 3 years and less than or equal to 21 years of age at study registration. 2. Diagnosis: Patients must have neoplastic meningitis secondary to an underlying leukemia/lymphoma or a solid tumor (including primary CNS tumors or carcinomas of unknown primary site) for which there is no conventional therapy. Patients with CNS leukemia/lymphoma must be refractory to conventional therapy, including XRT (i.e., 2nd or greater relapse). Neoplastic meningitis is defined as follows: (a)Leukemia/Lymphoma: CSF cell count over 5/µL AND evidence of blast cells on cytospin preparation or by cytology or (b) Solid tumor: Presence of tumor cells on cytospin preparation or cytology OR the unequivocal presence of meningeal disease on MRI scans. 3. Patients who have leukemia/lymphoma: Patients with CNS leukemia or lymphoma must have a negative bone marrow aspirate assessed within two weeks prior to registration. 4. Performance Status (Appendix III of full protocol): Karnofsky Performance Scale (KPS for greater than 16 yrs of age) or Lansky Performance Score (LPS for less than or equal to 16 years of age) greater than or equal to 60 assessed within two weeks prior to registration. Patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purposes of the performance score. 5. Recovery from Prior Therapy: Patients must have recovered from the acute neurotoxic effects of all prior chemotherapy, biological therapy, immunotherapy, or radiotherapy prior to entering this study and must be without uncontrolled significant systemic illness 5.1 Chemo: 1. Patients must have received their last dose of systemically administered therapy specifically for the treatment of their leptomeningeal disease (must be discussed with study chair) at least three (3) weeks prior to study registration. 2. Patients must have received their last dose of intrathecal therapy at least one (1) week (2 weeks if intrathecal DepoCyt) prior to study registration. 5.2 XRT: Patients must have had their last fraction of craniospinal irradiation greater than or equal to 8 weeks prior to study registration. 6. The following laboratory values must be assessed within two (2) weeks prior to registration. Laboratory tests should be repeated within 48 hours of beginning therapy, if there has been a significant clinical change. 6.1 Electrolytes: 1. Sodium: greater than or equal to 125 and less than or equal to 150 mmol/L 2. Calcium: greater than or equal to 7 mg/dL 3. Magnesium: greater than or equal to 0.7 mmol/L 7. Intraventricular access device: Patients must have or be willing to have an intraventricular access device such as an Ommaya reservoir. 8. Female patients of childbearing potential must have a negative serum or urine pregnancy test prior to registration. Patient must not be breast-feeding. 9. Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study. 10. Signed informed consent according to institutional guidelines must be obtained. Exclusion Criteria: 1. CSF Flow: Patients with clinical evidence of obstructive hydrocephalus are not eligible for this protocol. Patients with compartmentalization of CSF flow, as documented by radioisotope Indium111 or Technetium99-DTPA flow study are not eligible for this protocol. Requirement for CSF flow studies are: 1.1 Solid or CNS tumor patients: Nuclear medicine CSF flow studies are required within 7 days prior to registration in all patients with underlying solid or CNS tumors. Informed consent must be obtained prior to the CSF flow study. 1.2 Leukemia or lymphoma patients: Nuclear medicine CSF flow studies are only required if CSF analysis or an MRI suggests that there may be a blockage to CSF flow. The study must be obtained within 7 days prior to registration. Informed consent must be obtained prior to the CSF flow study. 2. Underlying illness: Patients with any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise a patient's ability to tolerate this therapy. 3. Concomitant Therapy Patients receiving other therapy (either intrathecal or systemic) designed to treat their leptomeningeal disease are not eligible for this study. Note: Patients receiving concomitant chemotherapy to control systemic disease or bulk CNS disease will be eligible, provided that the systemic chemotherapy is not an investigational agent or one of the following: high-dose methotrexate (\> 1g/m2), high-dose cytarabine (\> 1g/m2), 5-fluorouracil, capecitabine, thiotepa, a nitrosourea, or topotecan. Please discuss plans for systemic therapy with the Study Chair prior to study entry. 4. Patients with a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt are not eligible unless they are completely shunt-independent, e.g., shunts that have an on/off valve that is always in the "off" position. 5. Patients must be free of uncontrolled infection, except HIV patients with AIDS-related lymphomatous meningitis. 6. Patients currently receiving or who have received an investigational agent within the14 days prior to study registration. The 14 day period should be extended if the investigational agent is known to have delayed toxicity. 7. Patients with impending spinal cord compression or other CNS involvement requiring emergent local XRT (e.g., acute visual loss secondary to optic nerve involvement). 8. Patients receiving concomitant radiation therapy to the CNS. Note: Patients may receive radiation therapy to extra-CNS sites, e.g. painful bone metastases not in the craniospinal axis.