Phase 2 Clinical Trial of Intrathecal Topotecan in Children With Refractory Leptomeningeal Leukemia: A Children's Oncology Group Trial (P9962)†

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We performed a phase 2 study in children with recurrent or refractory leptomeningeal leukemia to determine the objective response rate after treatment with intrathecal (IT) topotecan.

Patients and Methods.

Patients received age-adjusted IT topotecan (0.4 mg/dose for patients >3 years of age) administered twice weekly (every 3–4 days) for 6 weeks during induction, weekly for 4 weeks during consolidation, and twice monthly for 4 months and then monthly thereafter during maintenance.


Twenty-two patients enrolled in the study, of whom 20 were eligible and assessable for toxicity and 16 were assessable for response. Of 16 patients, 6 (38%) had a complete response, 8 (50%) had stable disease, and 2 (13%) had progressive disease. The median event-free survival time (95% CI) was 3.1 (1.6–10.3) months and the median overall survival time (95% CI) was 18.0 (7.3–38.3) months. Eight patients (40%) experienced grade 3 or 4 adverse events. There were no grade 4 neurological events (Table III). Four patients experienced a total of 6 grade 3 neurological events including an olfactory seizure, a headache, transient grade 3 speech impairment, muscle weakness, motor neuropathy, and ataxia. Headache was the most common grade ≤2 neurologic event and two patients developed grade ≤2 arachnoiditis.


IT administration of topotecan was tolerable on this dose and schedule. The majority of adverse events were mild to moderate, reversible side effects. Complete central nervous system remissions were achieved in a subset of children with recurrent or refractory central nervous system leukemia. Pediatr Blood Cancer 2012; 58: 362–365. © 2011 Wiley Periodicals, Inc.

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