Expanded therapeutic options are warranted for patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations. The present phase 1, multicenter, open-label, dose-escalation and dose-expansion study was conducted to assess the safety, pharmacokinetics, and efficacy of multiple-dose monotherapy of the FLT3 inhibitor, quizartinib, in Japanese patients with R/R AML. Patients received oral quizartinib, once daily, under fasting conditions in 28-day cycles. Sixteen patients (median age, 68.0 years; male, 56.3%; FLT3-ITD positive, 43.8%) received quizartinib (9, 3, and 4 patients at 20, 30, and 60 mg/day, respectively; median treatment duration, 95.0 days; median relative dose intensity, 100.0%). No dose-limiting toxicities were observed. The most common treatment-emergent adverse events were electrocardiogram QT prolonged (43.8%, grade 1 or 2) followed by nausea and pyrexia (37.5% each). No quizartinib-related deaths were reported. A dose-dependent increase of quizartinib and its active metabolite AC886 levels was observed at the steady state. The composite complete remission rate was 37.5%. Quizartinib was well tolerated in Japanese R/R AML patients at doses up to 60 mg/day; quizartinib 60 mg/day was considered as the recommended dose for the Japanese patient population in a subsequent study.Trial registration ClinicalTrials.gov identifier NCT02675478.

中文翻译：

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在一项1期研究中，quizartinib在日本复发或难治性急性髓细胞性白血病患者中的安全性和药代动力学。

对于患有FMS样酪氨酸激酶3内部串联重复（FLT3-ITD）突变的复发性或难治性（R / R）急性髓细胞性白血病（AML）的患者，应扩大治疗选择范围。目前进行的第1期，多中心，开放标签，剂量递增和剂量扩展研究旨在评估日本R / R AML患者中FLT3抑制剂quizartinib的多剂量单药治疗的安全性，药代动力学和疗效。患者在禁食条件下，每天28天，每天一次口服quizartinib。16例患者（中位年龄为68.0岁；男性为56.3％； FLT3-ITD阳性为43.8％）接受quizartinib（9、3和4例患者，分别为20、30和60 mg /天；中位治疗时间为95.0天；中位数相对剂量强度，100.0％）。没有观察到剂量限制性毒性。最常见的治疗急救不良事件是心电图QT延长（43.8％，1或2级），其次是恶心和发热（分别为37.5％）。没有报道与奎扎替尼相关的死亡。在稳定状态下观察到奎扎替尼及其活性代谢产物AC886水平的剂量依赖性增加。综合完全缓解率为37.5％。日本R / R AML患者对Quizartinib的耐受性高达60 mg /天。在随后的研究中，将60 mg /天的quizartinib作为日本患者人群的推荐剂量。试验注册ClinicalTrials.gov标识符NCT02675478。在稳定状态下观察到奎扎替尼及其活性代谢产物AC886水平的剂量依赖性增加。综合完全缓解率为37.5％。日本R / R AML患者对Quizartinib的耐受性高达60 mg /天。在随后的研究中，将60 mg /天的quizartinib作为日本患者人群的推荐剂量。试验注册ClinicalTrials.gov标识符NCT02675478。在稳定状态下观察到奎扎替尼及其活性代谢产物AC886水平的剂量依赖性增加。综合完全缓解率为37.5％。日本R / R AML患者对Quizartinib的耐受性高达60 mg /天。在随后的研究中，将60 mg /天的quizartinib作为日本患者人群的推荐剂量。试验注册ClinicalTrials.gov标识符NCT02675478。