International Journal of Hematology

DOI: 10.1007/s12185-019-02709-8 Pages: 654-664

Safety and pharmacokinetics of quizartinib in Japanese patients with relapsed or refractory acute myeloid leukemia in a phase 1 study

1. NTT Medical Center Tokyo

2. Gunma University Hospital

3. National Hospital Organization Kyushu Cancer Center

4. University of Fukui Hospital

5. National Hospital Organization Nagoya Medical Center

6. Nagasaki University Hospital

7. Daiichi Sankyo Co., Ltd

8. Juntendo University Urayasu Hospital

Correspondence to:
Kensuke Usuki
Tel: +81-3-3448-6111



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 identifier NCT02675478.

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