Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase

Results from a phase II trial

Lia Gore, Pamela R. Kearns, Maria Lucia de Martino Lee, Carmino Antonio De Souza, Yves Bertrand, Nobuko Hijiya, Linda Stork, Nack Gyun Chung, Rocio Cardenas Cardos, Tapan Saikia, Franca Fagioli, Jong Jin Seo, Landman Parker Judith, Donna Lancaster, Andrew E. Place, Karen R. Rabin, Mariana Sacchi, Rene Swanink, C. Michel Zwaan

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose Safe, effective treatments are needed for pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP). Dasatinib is approved for treatment of adults and children with CML-CP. A phase I study determined suitable dosing for children with Philadelphia chromosome–positive (Ph+) leukemias. Methods CA180-226/NCT00777036 is a phase II, open-label, nonrandomized prospective trial of patients, 18 years of age receiving dasatinib. There are three cohorts: (1) imatinib-resistant/intolerant CML-CP, (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension. Major cytogenetic response . 30% for imatinib-resistant/intolerant patients and complete cytogenetic response (CCyR) . 55% for newly diagnosed patients were of clinical interest. Results Of 113 patients with CML-CP, 14 (48%) who were imatinib-resistant/intolerant and 61 (73%) who were newly diagnosed remained on treatment at time of analysis. Major cytogenetic response . 30% was reached by 3 months in the imatinib-resistant/intolerant group and CCyR . 55% was reached by 6 months in the newly diagnosed CML-CP group. CCyR and major molecular response by 12 months, respectively, were 76% and 41% in the imatinib-resistant/intolerant group and 92% and 52% in newly diagnosed CML-CP group. Progression-free survival by 48 months was 78% and 93% in the imatinib-resistant/intolerant and newly diagnosed CML-CP groups, respectively. No dasatinib-related pleural or pericardial effusion, pulmonary edema, or pulmonary arterial hypertension were reported. Bone growth and development events were reported in 4% of patients. Conclusion In the largest prospective trial to date in children with CML-CP, we demonstrate that dasatinib is a safe, effective treatment of pediatric CML-CP. Target responses to first- or second-line dasatinib were met early, and deep molecular responses were observed. Safety of dasatinib in pediatric patients was similar to that observed in adults; however, no cases of pleural or pericardial effusion or pulmonary arterial hypertension were reported.

Original languageEnglish (US)
Pages (from-to)1330-1338
Number of pages9
JournalJournal of Clinical Oncology
Volume36
Issue number13
DOIs
StatePublished - May 1 2018

Fingerprint

Leukemia, Myeloid, Chronic Phase
Pediatrics
Cytogenetics
Pericardial Effusion
Bone Development
Pleural Effusion
Pulmonary Hypertension
Dasatinib
Blast Crisis
Pulmonary Edema
Therapeutics
Imatinib Mesylate
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Growth and Development
Powders
Tablets
Disease-Free Survival
Suspensions
Leukemia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gore, L., Kearns, P. R., de Martino Lee, M. L., De Souza, C. A., Bertrand, Y., Hijiya, N., ... Zwaan, C. M. (2018). Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase: Results from a phase II trial. Journal of Clinical Oncology, 36(13), 1330-1338. https://doi.org/10.1200/JCO.2017.75.9597

Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase : Results from a phase II trial. / Gore, Lia; Kearns, Pamela R.; de Martino Lee, Maria Lucia; De Souza, Carmino Antonio; Bertrand, Yves; Hijiya, Nobuko; Stork, Linda; Chung, Nack Gyun; Cardos, Rocio Cardenas; Saikia, Tapan; Fagioli, Franca; Seo, Jong Jin; Judith, Landman Parker; Lancaster, Donna; Place, Andrew E.; Rabin, Karen R.; Sacchi, Mariana; Swanink, Rene; Zwaan, C. Michel.

In: Journal of Clinical Oncology, Vol. 36, No. 13, 01.05.2018, p. 1330-1338.

Research output: Contribution to journalArticle

Gore, L, Kearns, PR, de Martino Lee, ML, De Souza, CA, Bertrand, Y, Hijiya, N, Stork, L, Chung, NG, Cardos, RC, Saikia, T, Fagioli, F, Seo, JJ, Judith, LP, Lancaster, D, Place, AE, Rabin, KR, Sacchi, M, Swanink, R & Zwaan, CM 2018, 'Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase: Results from a phase II trial', Journal of Clinical Oncology, vol. 36, no. 13, pp. 1330-1338. https://doi.org/10.1200/JCO.2017.75.9597
Gore, Lia ; Kearns, Pamela R. ; de Martino Lee, Maria Lucia ; De Souza, Carmino Antonio ; Bertrand, Yves ; Hijiya, Nobuko ; Stork, Linda ; Chung, Nack Gyun ; Cardos, Rocio Cardenas ; Saikia, Tapan ; Fagioli, Franca ; Seo, Jong Jin ; Judith, Landman Parker ; Lancaster, Donna ; Place, Andrew E. ; Rabin, Karen R. ; Sacchi, Mariana ; Swanink, Rene ; Zwaan, C. Michel. / Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase : Results from a phase II trial. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 13. pp. 1330-1338.
@article{8930672ae27e43889a56fd69ea8005f9,
title = "Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase: Results from a phase II trial",
abstract = "Purpose Safe, effective treatments are needed for pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP). Dasatinib is approved for treatment of adults and children with CML-CP. A phase I study determined suitable dosing for children with Philadelphia chromosome–positive (Ph+) leukemias. Methods CA180-226/NCT00777036 is a phase II, open-label, nonrandomized prospective trial of patients, 18 years of age receiving dasatinib. There are three cohorts: (1) imatinib-resistant/intolerant CML-CP, (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension. Major cytogenetic response . 30{\%} for imatinib-resistant/intolerant patients and complete cytogenetic response (CCyR) . 55{\%} for newly diagnosed patients were of clinical interest. Results Of 113 patients with CML-CP, 14 (48{\%}) who were imatinib-resistant/intolerant and 61 (73{\%}) who were newly diagnosed remained on treatment at time of analysis. Major cytogenetic response . 30{\%} was reached by 3 months in the imatinib-resistant/intolerant group and CCyR . 55{\%} was reached by 6 months in the newly diagnosed CML-CP group. CCyR and major molecular response by 12 months, respectively, were 76{\%} and 41{\%} in the imatinib-resistant/intolerant group and 92{\%} and 52{\%} in newly diagnosed CML-CP group. Progression-free survival by 48 months was 78{\%} and 93{\%} in the imatinib-resistant/intolerant and newly diagnosed CML-CP groups, respectively. No dasatinib-related pleural or pericardial effusion, pulmonary edema, or pulmonary arterial hypertension were reported. Bone growth and development events were reported in 4{\%} of patients. Conclusion In the largest prospective trial to date in children with CML-CP, we demonstrate that dasatinib is a safe, effective treatment of pediatric CML-CP. Target responses to first- or second-line dasatinib were met early, and deep molecular responses were observed. Safety of dasatinib in pediatric patients was similar to that observed in adults; however, no cases of pleural or pericardial effusion or pulmonary arterial hypertension were reported.",
author = "Lia Gore and Kearns, {Pamela R.} and {de Martino Lee}, {Maria Lucia} and {De Souza}, {Carmino Antonio} and Yves Bertrand and Nobuko Hijiya and Linda Stork and Chung, {Nack Gyun} and Cardos, {Rocio Cardenas} and Tapan Saikia and Franca Fagioli and Seo, {Jong Jin} and Judith, {Landman Parker} and Donna Lancaster and Place, {Andrew E.} and Rabin, {Karen R.} and Mariana Sacchi and Rene Swanink and Zwaan, {C. Michel}",
year = "2018",
month = "5",
day = "1",
doi = "10.1200/JCO.2017.75.9597",
language = "English (US)",
volume = "36",
pages = "1330--1338",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "13",

}

TY - JOUR

T1 - Dasatinib in pediatric patients with chronic myeloid leukemia in chronic phase

T2 - Results from a phase II trial

AU - Gore, Lia

AU - Kearns, Pamela R.

AU - de Martino Lee, Maria Lucia

AU - De Souza, Carmino Antonio

AU - Bertrand, Yves

AU - Hijiya, Nobuko

AU - Stork, Linda

AU - Chung, Nack Gyun

AU - Cardos, Rocio Cardenas

AU - Saikia, Tapan

AU - Fagioli, Franca

AU - Seo, Jong Jin

AU - Judith, Landman Parker

AU - Lancaster, Donna

AU - Place, Andrew E.

AU - Rabin, Karen R.

AU - Sacchi, Mariana

AU - Swanink, Rene

AU - Zwaan, C. Michel

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Purpose Safe, effective treatments are needed for pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP). Dasatinib is approved for treatment of adults and children with CML-CP. A phase I study determined suitable dosing for children with Philadelphia chromosome–positive (Ph+) leukemias. Methods CA180-226/NCT00777036 is a phase II, open-label, nonrandomized prospective trial of patients, 18 years of age receiving dasatinib. There are three cohorts: (1) imatinib-resistant/intolerant CML-CP, (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension. Major cytogenetic response . 30% for imatinib-resistant/intolerant patients and complete cytogenetic response (CCyR) . 55% for newly diagnosed patients were of clinical interest. Results Of 113 patients with CML-CP, 14 (48%) who were imatinib-resistant/intolerant and 61 (73%) who were newly diagnosed remained on treatment at time of analysis. Major cytogenetic response . 30% was reached by 3 months in the imatinib-resistant/intolerant group and CCyR . 55% was reached by 6 months in the newly diagnosed CML-CP group. CCyR and major molecular response by 12 months, respectively, were 76% and 41% in the imatinib-resistant/intolerant group and 92% and 52% in newly diagnosed CML-CP group. Progression-free survival by 48 months was 78% and 93% in the imatinib-resistant/intolerant and newly diagnosed CML-CP groups, respectively. No dasatinib-related pleural or pericardial effusion, pulmonary edema, or pulmonary arterial hypertension were reported. Bone growth and development events were reported in 4% of patients. Conclusion In the largest prospective trial to date in children with CML-CP, we demonstrate that dasatinib is a safe, effective treatment of pediatric CML-CP. Target responses to first- or second-line dasatinib were met early, and deep molecular responses were observed. Safety of dasatinib in pediatric patients was similar to that observed in adults; however, no cases of pleural or pericardial effusion or pulmonary arterial hypertension were reported.

AB - Purpose Safe, effective treatments are needed for pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP). Dasatinib is approved for treatment of adults and children with CML-CP. A phase I study determined suitable dosing for children with Philadelphia chromosome–positive (Ph+) leukemias. Methods CA180-226/NCT00777036 is a phase II, open-label, nonrandomized prospective trial of patients, 18 years of age receiving dasatinib. There are three cohorts: (1) imatinib-resistant/intolerant CML-CP, (2) imatinib-resistant/intolerant CML in accelerated/blast phase or Ph+ acute lymphoblastic leukemia (n = 17), and (3) newly diagnosed CML-CP treated with tablets or powder for oral suspension. Major cytogenetic response . 30% for imatinib-resistant/intolerant patients and complete cytogenetic response (CCyR) . 55% for newly diagnosed patients were of clinical interest. Results Of 113 patients with CML-CP, 14 (48%) who were imatinib-resistant/intolerant and 61 (73%) who were newly diagnosed remained on treatment at time of analysis. Major cytogenetic response . 30% was reached by 3 months in the imatinib-resistant/intolerant group and CCyR . 55% was reached by 6 months in the newly diagnosed CML-CP group. CCyR and major molecular response by 12 months, respectively, were 76% and 41% in the imatinib-resistant/intolerant group and 92% and 52% in newly diagnosed CML-CP group. Progression-free survival by 48 months was 78% and 93% in the imatinib-resistant/intolerant and newly diagnosed CML-CP groups, respectively. No dasatinib-related pleural or pericardial effusion, pulmonary edema, or pulmonary arterial hypertension were reported. Bone growth and development events were reported in 4% of patients. Conclusion In the largest prospective trial to date in children with CML-CP, we demonstrate that dasatinib is a safe, effective treatment of pediatric CML-CP. Target responses to first- or second-line dasatinib were met early, and deep molecular responses were observed. Safety of dasatinib in pediatric patients was similar to that observed in adults; however, no cases of pleural or pericardial effusion or pulmonary arterial hypertension were reported.

UR - http://www.scopus.com/inward/record.url?scp=85046036154&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046036154&partnerID=8YFLogxK

U2 - 10.1200/JCO.2017.75.9597

DO - 10.1200/JCO.2017.75.9597

M3 - Article

VL - 36

SP - 1330

EP - 1338

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 13

ER -