臨床研究等提出・公開システム

Phase 2 open-label, single-arm study of Quizartinib (AC220) monotherapy in Japanese patients with FLT3-ITD positive refractory or relapsed acute myeloid leukemia

Phase 2 study of quizartinib

37

The median age of all registered patients was 65.0 years and 59.5% of patients were women. The median body mass index was 20.9 kg/m2 and nearly half of the patients had an ECOG PS of 0 (48.6%). Twenty-four (64.9%) were relapsed patients and 13 (35.1%) were refractory patients.

A total of 37 patients were registered by the cut-off date (26 Feb 2018). A total of 28 patients discontinued the study treatment for the following reasons: 15 patients required transplantation, 12 patients had progressive disease, and 1 patient had an adverse event (AE), and 14 patients discontinued the study due to death. Nine patients were ongoing treatment as of the data cut-off date.

All 37 patients experienced at least one treatment emergent AE (TEAE) during the study. The most frequently reported TEAEs were febrile neutropenia in 16 (43.2%), platelet count decreased in 14 (37.8%), electrocardiogram QT prolonged in 13 (35.1%), nausea in 11 (29.7%), and anemia in 10 (27.0%) patients. TEAEs of grade >= 3 were reported in 34 (91.9%) patients; the most frequently reported were febrile neutropenia in 14 (37.8%), platelet count decreased in 11 (29.7%), anemia in 9 (24.3%), neutrophil count decreased in 8 (21.6%), and white blood cell count decreased in 8 (21.6%) patients. Among them, serious TEAEs were reported in 17 (45.9%) patients, the most frequently reported (>= 2 patients) were febrile neutropenia [6 (16.2%) patients], followed by bacteremia and sepsis [2 (5.4%) patients each]. TEAEs associated with treatment discontinuation were reported in 2 patients (5.4%). One patient experienced drug-related lipase increased. Progressive disease in one patient resulted in death, which was considered as a TEAE associated with treatment discontinuation due to a fatal event (drug-unrelated).

The CRc rate, the primary endpoint, was 53.8%, with a 90% CI of 36.2-70.8 for evaluable patients (n = 26) in the efficacy analysis set. As the lower limit of the 90% CI was greater than 23.5%, the null hypothesis was rejected and the primary objective of this study was met.

The median duration of CRc was 16.1 weeks (95% CI: 4.7-24.6). The response rate was 77.8% (95% CI: 57.7-91.4). The median OS was 34.1 weeks (95% CI: 27.1 to not reached). The median EFS and LFS were 12.7 weeks (95% CI: 0.1-24.7) and 16.1 weeks (95% CI: 4.7-24.6), respectively. Overall, 12 of 32 (37.5%) patients underwent HSCT following quizartinib treatment.

Treatment with quizartinib monotherapy was well tolerated and resulted in clinically meaningful reductions in blast count in Japanese patients with FLT3-ITD positive relapsed or refractory AML.

Aug. 31, 2019

https://link.springer.com/article/10.1007%2Fs12185-019-02727-6

Yes

Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/ Supporting Documents: - Study Protocol - Statistical Analysis Plan - Clinical Study Report Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication. Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent. URL: https://vivli.org/ourmember/daiichi-sankyo/

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

Jan. 24, 2017

Interventional

Multi-center, single-arm, open label

treatment purpose

2

- AML patients in first relapse or refractory after all prior therapy.
- Presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood.
- ECOG Performance Status(PS) of 0 to 2.

- Diagnosis of acute promyelocytic leukemia.
- AML secondary to prior chemotherapy for other neoplasms.
- Persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML therapy.
- Prior treatment with a FLT3 targeted therapy.
- Active infection not well controlled by antibacterial, antifungal and/or antiviral therapy.

Both

Acute myeloid leukemia (AML)

investigational material(s)
Generic name etc : AC220
INN of investigational material : Quizartinib
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : Oral administration once daily

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

efficacy
Composite complete remission rate
- Tumor response will be assessed by the bone marrow findings, and absolute neutrophil count and platelet count in the peripheral blood.

safety
efficacy
pharmacokinetics
- Best response, response rate, overall survival, event free survival, leukemia-free survival
- Safety
- Pharmacokinetics
- Tumor response will be assessed by the bone marrow findings, and absolute neutrophil count and platelet count in the peripheral blood.
- To assess the safety according to CTCAE
- To measure the concentration of quizartinib in the peripheral blood.

Dec. 20, 2016