Phase 2 Study of Nilotinib in Pediatric Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia

Nobuko Hijiya, Alexey Maschan, Carmelo Rizzari, Hiroyuki Shimada, Carlo Dufour, Hiroaki Goto, Hyoung Jin Kang, Terri Guinipero, Zeynep Karakas, Francisco Bautista, Stéphane Ducassou, Keon Hee YOO, Christian Michel Zwaan, Frédéric Millot, Paola Aimone, Alex Allepuz, Sara Quenet, Florence Hourcade-Potelleret, Sabine Hertle and Darintr Sosothikul

Key Points

  • Nilotinib demonstrated efficacy and a manageable safety profile in pediatric patients with newly diagnosed and pretreated Ph+ CML-CP.


Chronic myeloid leukemia (CML) is rare in children and accounts for {less than or equal to} 15% of all myeloid leukemia cases. When we initiated this study with nilotinib, imatinib was the only tyrosine kinase inhibitor indicated for pediatric patients with Philadelphia chromosome-positive (Ph+) CML in chronic phase (CP); alternative treatment options were needed, particularly for patients who developed resistance/intolerance (R/I) to imatinib. This phase 2 study enrolled pediatric patients with either Ph+ CML-CP R/I to imatinib/dasatinib or newly diagnosed Ph+ CML-CP. Data presented are from analyses with up to 24 cycles' minimum follow-up (1 cycle = 28 days). Fifty-nine patients with Ph+ CML-CP were enrolled and 58 were treated (R/I, n = 33; newly diagnosed, n = 25). Major molecular response (MMR) rate at cycle 6 in the R/I cohort was 39.4% (primary endpoint); 57.6% and 81.8% of patients achieved or maintained MMR and complete cytogenetic response (CCyR), respectively, by 24 cycles. In patients with newly diagnosed disease, rates of MMR by cycle 12 and CCyR at cycle 12 were 64.0% each (primary endpoints); by cycle 24, cumulative MMR and CCyR rates were 68.0% and 84.0%, respectively. The safety profile of nilotinib in pediatric patients was generally comparable with the known safety profile in adults, although cardiovascular events were not observed in this study and hepatic laboratory abnormalities were more frequent; no new safety signals were identified. In summary, nilotinib demonstrated efficacy and a manageable safety profile in pediatric patients with Ph+ CML-CP. This trial was registered at as #NCT01844765.

  • Submitted February 7, 2019.
  • Revision received September 9, 2019.
  • Accepted August 17, 2019.