A phase 2 study of nilotinib in pediatric patients with CML: Long-term update on growth retardation and safety

Nobuko Hijiya*, Alexey Maschan, Carmelo Rizzari, Hiroyuki Shimada, Carlo Dufour, Hiroaki Goto, Hyoung Jin Kang, Terri Guinipero, Zeynep Karakas, Francisco Bautista, Stephane Ducassou, Keon Hee Yoo, Christian Michel Zwaan, Frederic Millot, Briana Patterson, Jill Samis, Paola Aimone, Alex Allepuz, Ksenia Titorenko, Darintr Sosothikul

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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The phase 2, open-label study (DIALOG) of nilotinib in pediatric patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) met its coprimary end points, showing sustained nilotinib efficacy in patients with newly diagnosed (ND) or imatinib/dasatinib resistant/intolerant (R/I) CML. This update assessed growth and safety profiles in patients who had completed ≥48, 28-day treatment cycles of nilotinib 230 mg/m2 twice daily, or previously discontinued the study. Height was assessed regularly and reported using standard deviation scores (SDSs) based on World Health Organization growth charts. All data were summarized descriptively (cutoff, 6 March 2019). Overall, 33 patients in the R/I cohort and 25 patients in the ND cohort received nilotinib. Each cohort showed a negative slope in height SDS over the course of the study, indicating attenuated growth rates during nilotinib treatment: overall median change from baseline in height SDS after 48 cycles was 20.54 SDS (range, 2 1.6 to 0.4) and 20.91 SDS (21.4 to 20.1) in R/I and ND cohorts, respectively. Patients in the R/I cohort were shorter at baseline than those in the ND cohort, and remained so throughout the study. The most common all-cause adverse events were increased blood bilirubin (53.4%), headache (46.6%), pyrexia (37.9%), and increased alanine transferase (36.2%). Apart from the impact on growth, the safety profile of nilotinib was generally consistent with previous reports. This study was registered on www.clinicaltrials.gov at #NCT01844765.

Original languageEnglish
Pages (from-to)2925-2934
Number of pages10
JournalBlood advances
Issue number14
Publication statusPublished - 26 Jul 2021

Bibliographical note

Medical writing and editorial assistance were provided by Christine Elsner and Kyle Lambe (Synergy Medical Communications, London, United Kingdom) and supported by Novartis Pharmaceuticals Corporation.

This study was sponsored and funded by Novartis Pharmaceuticals Corporation.

Publisher Copyright:
© 2021 by The American Society of Hematology.

Research programs

  • EMC MM-02-54-03


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