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

• Status: Completed
• Trial end date: 2009-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well topotecan hydrochloride works in treating children with meningeal cancer that has not responded to previous treatment

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Topotecan

Criteria

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