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Safety and Pharmacokinetics of Quizartinib Combination Therapy With Standard Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia: Results from Two Phase 1 Trials in Japan and China.
Qi, Junyuan; Choi, Ilseung; Ota, Shuichi; Ichikawa, Satoshi; Fujishima, Naohito; Iida, Hiroatsu; Sugiura, Isamu; Sugiura, Koichi; Murata, Yasuharu; Inoue, Hiroyuki; Ohwada, Shoichi; Wang, Jianxiang.
Afiliación
  • Qi J; Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
  • Choi I; National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
  • Ota S; Sapporo Hokuyu Hospital, Sapporo, Japan.
  • Ichikawa S; Tohoku University Hospital, Sendai, Japan.
  • Fujishima N; Noshiro Kousei Medical Center, Akita, Japan.
  • Iida H; National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
  • Sugiura I; Toyohashi Hematology Oncology Clinic, Aichi, Japan.
  • Sugiura K; Daiichi Sankyo Co., Ltd, Tokyo, Japan.
  • Murata Y; Daiichi Sankyo Co., Ltd, Tokyo, Japan.
  • Inoue H; Daiichi Sankyo Co., Ltd, Tokyo, Japan.
  • Ohwada S; Daiichi Sankyo Co., Ltd, Tokyo, Japan.
  • Wang J; Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Clin Pharmacol Drug Dev ; 13(5): 560-571, 2024 May.
Article en En | MEDLINE | ID: mdl-38284515
ABSTRACT
Quizartinib is a potent, oral, second-generation, selective type II FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor. It has shown improved overall survival in a randomized, multinational, Phase 3 (QuANTUM-First) study in patients with FLT3-internal tandem duplication (ITD)-positive newly diagnosed acute myeloid leukemia. We conducted 2 Phase 1b studies in Japan and China to evaluate the safety, pharmacokinetics, and efficacy of quizartinib in combination with standard induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia. Quizartinib was started at a dose level of 20 mg/day and then escalated to 40 mg/day, the dose used in the Phase 3 study. Seven patients were enrolled according to the 3 + 3 dose-escalation method in each study, including 3 patients who were FLT3-ITD positive. No dose-limiting toxicities were observed at dose levels up to 40 mg/day in both studies. Grade 3 or higher, quizartinib-related, treatment-emergent adverse events included febrile neutropenia, hematologic toxicities, and infections. QT prolongation on electrocardiogram was observed in 5 patients. The pharmacokinetics of quizartinib and its metabolite AC886 were similar between the studies and consistent with previous findings in the United States. We confirmed the tolerability of Japanese and Chinese patients to the dose of quizartinib and chemotherapy regimens used in the QuANTUM-First study.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos de Fenilurea / Leucemia Mieloide Aguda / Protocolos de Quimioterapia Combinada Antineoplásica / Benzotiazoles / Tirosina Quinasa 3 Similar a fms / Quimioterapia de Consolidación Tipo de estudio: Clinical_trials / Diagnostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: Clin Pharmacol Drug Dev Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Compuestos de Fenilurea / Leucemia Mieloide Aguda / Protocolos de Quimioterapia Combinada Antineoplásica / Benzotiazoles / Tirosina Quinasa 3 Similar a fms / Quimioterapia de Consolidación Tipo de estudio: Clinical_trials / Diagnostic_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: Clin Pharmacol Drug Dev Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos