Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921

Pediatric patients; Intolerant; Chronic myeloid leukemia

Detalles Bibliográficos
Autores: Brivio, Erica, Edoardo, Pennesi, Willemse, Marieke E., Huitema, Alwin D. R., Jiang, Yilin, van Tinteren, Harm, Murillo-Sanjuán, Laura
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/11158
Acceso en línea:https://hdl.handle.net/11351/11158
http://hdl.handle.net/11351/11158
Access Level:acceso abierto
Palabra clave:Proteïnes quinases - Inhibidors - Ús terapèutic - Efectes secundaris
Leucèmia mieloide crònica - Tractament
DISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders::Leukemia, Myelogenous, Chronic, BCR-ABL Positive::Leukemia, Myeloid, Chronic-Phase
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors
Other subheadings::Other subheadings::Other subheadings::/adverse effects
ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::trastornos mieloproliferativos::leucemia mielogenosa crónica BCR-ABL positiva::leucemia mieloide de fase crónica
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas
Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos
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oai_identifier_str oai:recercat.cat:11351/11158
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921
title Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921
spellingShingle Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921
Brivio, Erica
Proteïnes quinases - Inhibidors - Ús terapèutic - Efectes secundaris
Leucèmia mieloide crònica - Tractament
DISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders::Leukemia, Myelogenous, Chronic, BCR-ABL Positive::Leukemia, Myeloid, Chronic-Phase
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors
Other subheadings::Other subheadings::Other subheadings::/adverse effects
ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::trastornos mieloproliferativos::leucemia mielogenosa crónica BCR-ABL positiva::leucemia mieloide de fase crónica
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas
Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos
title_short Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921
title_full Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921
title_fullStr Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921
title_full_unstemmed Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921
title_sort Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921
dc.creator.none.fl_str_mv Brivio, Erica
Edoardo, Pennesi
Willemse, Marieke E.
Huitema, Alwin D. R.
Jiang, Yilin
van Tinteren, Harm
Murillo-Sanjuán, Laura
author Brivio, Erica
author_facet Brivio, Erica
Edoardo, Pennesi
Willemse, Marieke E.
Huitema, Alwin D. R.
Jiang, Yilin
van Tinteren, Harm
Murillo-Sanjuán, Laura
author_role author
author2 Edoardo, Pennesi
Willemse, Marieke E.
Huitema, Alwin D. R.
Jiang, Yilin
van Tinteren, Harm
Murillo-Sanjuán, Laura
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Brivio E, Pennesi E, Willemse ME, Jiang Y] Department of Pediatric Oncology, Erasmus MC Sophia Children’s Hospital, Rotterdam, the Netherlands. Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. [Huitema ADR] Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. The Netherlands Cancer Institute, Amsterdam, the Netherlands. University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. [van Tinteren HDR] Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. [Murillo-Sanjuan L] Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Proteïnes quinases - Inhibidors - Ús terapèutic - Efectes secundaris
Leucèmia mieloide crònica - Tractament
DISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders::Leukemia, Myelogenous, Chronic, BCR-ABL Positive::Leukemia, Myeloid, Chronic-Phase
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors
Other subheadings::Other subheadings::Other subheadings::/adverse effects
ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::trastornos mieloproliferativos::leucemia mielogenosa crónica BCR-ABL positiva::leucemia mieloide de fase crónica
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas
Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos
topic Proteïnes quinases - Inhibidors - Ús terapèutic - Efectes secundaris
Leucèmia mieloide crònica - Tractament
DISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders::Leukemia, Myelogenous, Chronic, BCR-ABL Positive::Leukemia, Myeloid, Chronic-Phase
Other subheadings::Other subheadings::Other subheadings::/drug therapy
CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors
Other subheadings::Other subheadings::Other subheadings::/adverse effects
ENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::trastornos mieloproliferativos::leucemia mielogenosa crónica BCR-ABL positiva::leucemia mieloide de fase crónica
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas
Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos
description Pediatric patients; Intolerant; Chronic myeloid leukemia
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/11158
http://hdl.handle.net/11351/11158
url https://hdl.handle.net/11351/11158
http://hdl.handle.net/11351/11158
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Clinical Oncology;42(7)
https://doi.org/10.1200/JCO.23.00897
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society of Clinical Oncology
publisher.none.fl_str_mv American Society of Clinical Oncology
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869424426335862784
spelling Bosutinib in Resistant and Intolerant Pediatric Patients With Chronic Phase Chronic Myeloid Leukemia: Results From the Phase I Part of Study ITCC054/COG AAML1921Brivio, EricaEdoardo, PennesiWillemse, Marieke E.Huitema, Alwin D. R.Jiang, Yilinvan Tinteren, HarmMurillo-Sanjuán, LauraProteïnes quinases - Inhibidors - Ús terapèutic - Efectes secundarisLeucèmia mieloide crònica - TractamentDISEASES::Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders::Leukemia, Myelogenous, Chronic, BCR-ABL Positive::Leukemia, Myeloid, Chronic-PhaseOther subheadings::Other subheadings::Other subheadings::/drug therapyCHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase InhibitorsOther subheadings::Other subheadings::Other subheadings::/adverse effectsENFERMEDADES::enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::trastornos mieloproliferativos::leucemia mielogenosa crónica BCR-ABL positiva::leucemia mieloide de fase crónicaOtros calificadores::Otros calificadores::Otros calificadores::/farmacoterapiaCOMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasasOtros calificadores::Otros calificadores::Otros calificadores::/efectos adversosPediatric patients; Intolerant; Chronic myeloid leukemiaPacientes pediátricos; Intolerantes; Leucemia mieloide crónicaPacients pediàtrics; Intolerants; Leucèmia mieloide crònicaPurpose Bosutinib is approved for adults with chronic myeloid leukemia (CML): 400 mg once daily in newly diagnosed (ND); 500 mg once daily in resistant/intolerant (R/I) patients. Bosutinib has a different tolerability profile than other tyrosine kinase inhibitors (TKIs) and potentially less impact on growth (preclinical data). The primary objective of this first-in-child trial was to determine the recommended phase II dose (RP2D) for pediatric R/I and ND patients. Patients and Methods In the phase I part of this international, open-label trial (ClinicalTrials.gov identifier: NCT04258943), children age 1-18 years with R/I (per European LeukemiaNet 2013) Ph+ CML were enrolled using a 6 + 4 design, testing 300, 350, and 400 mg/m2 once daily with food. The RP2D was the dose resulting in 0/6 or 1/10 dose-limiting toxicities (DLTs) during the first cycle and achieving adult target AUC levels for the respective indication. As ND participants were only enrolled in phase II, the ND RP2D was selected based on data from R/I patients. Results Thirty patients were enrolled; 27 were evaluable for DLT: six at 300 mg/m2, 11 at 350 mg/m2 (one DLT), and 10 at 400 mg/m2 (one DLT). The mean AUCs at 300 mg/m2, 350 mg/m2, and 400 mg/m2 were 2.20 μg h/mL, 2.52 μg h/mL, and 2.66 μg h/mL, respectively. The most common adverse event was diarrhea (93%; ≥grade 3: 11%). Seven patients stopped because of intolerance and eight because of insufficient response. Complete cytogenetic and major molecular response to bosutinib appeared comparable with other published phase I/II trials with second-generation TKIs in children. Conclusion Bosutinib was safe and effective. The pediatric RP2D was 400 mg/m2 once daily (max 600 mg/d) with food in R/I patients and 300 mg/m2 once daily (max 500 mg/d) with food in ND patients, which achieved targeted exposures as per adult experience.Sponsorship for the study was provided by Erasmus MC/Sophia Children's Hospital, Department of Pediatrics, Rotterdam, the Netherlands.American Society of Clinical OncologyInstitut Català de la Salut[Brivio E, Pennesi E, Willemse ME, Jiang Y] Department of Pediatric Oncology, Erasmus MC Sophia Children’s Hospital, Rotterdam, the Netherlands. Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. [Huitema ADR] Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. The Netherlands Cancer Institute, Amsterdam, the Netherlands. University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. [van Tinteren HDR] Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. [Murillo-Sanjuan L] Vall d’Hebron Hospital Universitari, Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/11158http://hdl.handle.net/11351/11158Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésJournal of Clinical Oncology;42(7)https://doi.org/10.1200/JCO.23.00897Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/111582026-05-29T05:05:01Z
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