Data from Pharmacokinetics of Nilotinib in Pediatric Patients with Philadelphia Chromosome–Positive Chronic Myeloid Leukemia or Acute Lymphoblastic Leukemia

Abstract

<div>AbstractPurpose:<p>We investigated nilotinib exposure in pediatric patients with chronic myeloid leukemia (CML) or Philadelphia chromosome–positive (Ph<sup>+</sup>) acute lymphoblastic leukemia (ALL) resistant to, relapsed on, refractory to, or intolerant of previous treatment.</p>Patients and Methods:<p>Fifteen patients (aged 1–<18 years) with CML resistant to or intolerant of imatinib and/or dasatinib (<i>n</i> = 11) or Ph<sup>+</sup> ALL relapsed on or refractory to standard therapy (<i>n</i> = 4) enrolled in this phase I study. Nilotinib (230 mg/m<sup>2</sup> twice daily; equivalent to the adult 400-mg twice-daily dose) was administered orally in 12 or 24 cycles of 28 days. The primary objective was to characterize the pharmacokinetics of nilotinib in pediatric patients.</p>Results:<p>The area under the concentration–time curve at steady state was slightly lower in pediatric patients versus adults (14,751.4 vs. 17,102.9 ng/h/mL); the geometric mean ratio (GMR; pediatric:adult) was 0.86 [90% confidence interval (CI), 0.70–1.06]. Body surface area–adjusted systemic clearance was slightly higher in pediatric versus adult patients (GMR, 1.30; 90% CI, 1.04–1.62). Nilotinib was generally well tolerated. The most common adverse events were headache, vomiting, increased blood bilirubin, and rash. Three patients with CML achieved major molecular response, and three with Ph<sup>+</sup> ALL achieved complete remission.</p>Conclusions:<p>Nilotinib 230 mg/m<sup>2</sup> twice daily in pediatric patients provided a pharmacokinetics and safety profile comparable with the adult reference dose; clinical activity was demonstrated in both CML and Ph<sup>+</sup> ALL. This dose is recommended for further evaluation in pediatric patients. The safety profile was consistent with that in adults.</p></div>