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, Darintr Sosothikul

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Abstract

Chronic myeloid leukemia (CML) is rare in children and accounts for £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 (Ph1) CML in chronic phase (CP); alternative treatment options were needed, particularly for patients who developed resistance or intolerance (R/I) to imatinib. This phase 2 study enrolled pediatric patients with either Ph1 CML-CP R/I to imatinib or dasatinib or newly diagnosed Ph1 CML-CP. Data presented are from analyses with minimum follow-up of up to 24 cycles (1 cycle is 28 days). Fifty-nine patients with Ph1 CML-CP were enrolled, and 58 were treated (R/I, n 5 33; newly diagnosed, n 5 25). Major molecular response (MMR) rate at cycle 6 in the R/I cohort was 39.4% (primary end point); 57.6% of patients achieved or maintained MMR and 81.8% achieved or maintained complete cytogenetic response (CCyR) 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 end points); 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 Ph1 CML-CP. This trial was registered at www.clinicaltrials.gov as #NCT01844765. (Blood. 2019;134(23):2036-2045).

Original languageEnglish
Pages (from-to)2036-2045
Number of pages10
JournalBlood
Volume134
Issue number23
DOIs
Publication statusPublished - 2019 Dec 5

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Pediatrics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic Phase
Cytogenetics
Safety
Protein-Tyrosine Kinases
Blood
Myeloid Leukemia
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Imatinib Mesylate
Liver

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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Phase 2 study of nilotinib in pediatric patients with Philadelphia chromosome–positive chronic myeloid leukemia. / Hijiya, Nobuko; Maschan, Alexey; Rizzari, Carmelo; Shimada, Hiroyuki; Dufour, Carlo; Goto, Hiroaki; Kang, Hyoung Jin; Guinipero, Terri; Karakas, Zeynep; Bautista, Francisco; Ducassou, Stéphane; Yoo, Keon Hee; Zwaan, Christian Michel; Millot, Frédéric; Aimone, Paola; Allepuz, Alex; Quenet, Sara; Hourcade-Potelleret, Florence; Hertle, Sabine; Sosothikul, Darintr.

In: Blood, Vol. 134, No. 23, 05.12.2019, p. 2036-2045.

Research output: Contribution to journalArticle

Hijiya, N, Maschan, A, Rizzari, C, Shimada, H, Dufour, C, Goto, H, Kang, HJ, Guinipero, T, Karakas, Z, Bautista, F, Ducassou, S, Yoo, KH, Zwaan, CM, Millot, F, Aimone, P, Allepuz, A, Quenet, S, Hourcade-Potelleret, F, Hertle, S & Sosothikul, D 2019, 'Phase 2 study of nilotinib in pediatric patients with Philadelphia chromosome–positive chronic myeloid leukemia', Blood, vol. 134, no. 23, pp. 2036-2045. https://doi.org/10.1182/blood.2019000069
Hijiya, Nobuko ; Maschan, Alexey ; Rizzari, Carmelo ; Shimada, Hiroyuki ; Dufour, Carlo ; Goto, Hiroaki ; Kang, Hyoung Jin ; Guinipero, Terri ; Karakas, Zeynep ; Bautista, Francisco ; Ducassou, Stéphane ; Yoo, Keon Hee ; Zwaan, Christian Michel ; Millot, Frédéric ; Aimone, Paola ; Allepuz, Alex ; Quenet, Sara ; Hourcade-Potelleret, Florence ; Hertle, Sabine ; Sosothikul, Darintr. / Phase 2 study of nilotinib in pediatric patients with Philadelphia chromosome–positive chronic myeloid leukemia. In: Blood. 2019 ; Vol. 134, No. 23. pp. 2036-2045.
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abstract = "Chronic myeloid leukemia (CML) is rare in children and accounts for £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 (Ph1) CML in chronic phase (CP); alternative treatment options were needed, particularly for patients who developed resistance or intolerance (R/I) to imatinib. This phase 2 study enrolled pediatric patients with either Ph1 CML-CP R/I to imatinib or dasatinib or newly diagnosed Ph1 CML-CP. Data presented are from analyses with minimum follow-up of up to 24 cycles (1 cycle is 28 days). Fifty-nine patients with Ph1 CML-CP were enrolled, and 58 were treated (R/I, n 5 33; newly diagnosed, n 5 25). Major molecular response (MMR) rate at cycle 6 in the R/I cohort was 39.4{\%} (primary end point); 57.6{\%} of patients achieved or maintained MMR and 81.8{\%} achieved or maintained complete cytogenetic response (CCyR) 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 end points); 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 Ph1 CML-CP. This trial was registered at www.clinicaltrials.gov as #NCT01844765. (Blood. 2019;134(23):2036-2045).",
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AU - Hijiya, Nobuko

AU - Maschan, Alexey

AU - Rizzari, Carmelo

AU - Shimada, Hiroyuki

AU - Dufour, Carlo

AU - Goto, Hiroaki

AU - Kang, Hyoung Jin

AU - Guinipero, Terri

AU - Karakas, Zeynep

AU - Bautista, Francisco

AU - Ducassou, Stéphane

AU - Yoo, Keon Hee

AU - Zwaan, Christian Michel

AU - Millot, Frédéric

AU - Aimone, Paola

AU - Allepuz, Alex

AU - Quenet, Sara

AU - Hourcade-Potelleret, Florence

AU - Hertle, Sabine

AU - Sosothikul, Darintr

PY - 2019/12/5

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N2 - Chronic myeloid leukemia (CML) is rare in children and accounts for £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 (Ph1) CML in chronic phase (CP); alternative treatment options were needed, particularly for patients who developed resistance or intolerance (R/I) to imatinib. This phase 2 study enrolled pediatric patients with either Ph1 CML-CP R/I to imatinib or dasatinib or newly diagnosed Ph1 CML-CP. Data presented are from analyses with minimum follow-up of up to 24 cycles (1 cycle is 28 days). Fifty-nine patients with Ph1 CML-CP were enrolled, and 58 were treated (R/I, n 5 33; newly diagnosed, n 5 25). Major molecular response (MMR) rate at cycle 6 in the R/I cohort was 39.4% (primary end point); 57.6% of patients achieved or maintained MMR and 81.8% achieved or maintained complete cytogenetic response (CCyR) 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 end points); 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 Ph1 CML-CP. This trial was registered at www.clinicaltrials.gov as #NCT01844765. (Blood. 2019;134(23):2036-2045).

AB - Chronic myeloid leukemia (CML) is rare in children and accounts for £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 (Ph1) CML in chronic phase (CP); alternative treatment options were needed, particularly for patients who developed resistance or intolerance (R/I) to imatinib. This phase 2 study enrolled pediatric patients with either Ph1 CML-CP R/I to imatinib or dasatinib or newly diagnosed Ph1 CML-CP. Data presented are from analyses with minimum follow-up of up to 24 cycles (1 cycle is 28 days). Fifty-nine patients with Ph1 CML-CP were enrolled, and 58 were treated (R/I, n 5 33; newly diagnosed, n 5 25). Major molecular response (MMR) rate at cycle 6 in the R/I cohort was 39.4% (primary end point); 57.6% of patients achieved or maintained MMR and 81.8% achieved or maintained complete cytogenetic response (CCyR) 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 end points); 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 Ph1 CML-CP. This trial was registered at www.clinicaltrials.gov as #NCT01844765. (Blood. 2019;134(23):2036-2045).

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