Phase 1 Study of Quizartinib

A Phase 1, Open-Label, Dose Escalation Study of Quizartinib, An Oral FLT3 Inhibitor, in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia

This is a dose escalation study to evaluate the safety, tolerability, and pharmacokinetics of quizartinib for Japanese acute myeloid leukemia (AML) subjects.

Study Overview

• Status: Completed
• Conditions: Relapsed AML; Refractory AML
• Intervention / Treatment: Drug: AC220

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Relapsed or refractory AML
• AML for which no standard treatment is available
• ECOG Performance Status (PS) of 0 to 2

Exclusion Criteria:

• Acute Promyelocytic Leukemia
• chronic myelogenous leukemia in blast phase (BCR-ABL fusion gene positive)
• History of other malignancies within 3 years prior to enrollment, except curatively treated in-situ carcinoma, AML, or MDS.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AC220; This study will follow a mCRM (modified continual reassessment method) + EWOC (Escalation with Overdose Control) design.	Drug: AC220

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of subjects experiencing adverse events		first dose to follow-up, approximately 1 year
Cmax of quizartinib and its active metabolite	Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.	Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15
Tmax of quizartinib and its active metabolite	Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.	Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15
AUCtau of quizartinib and its active metabolite	Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.	Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15
Cmax,ss of quizartinib and its active metabolite	Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.	Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15
Ctrough of quizartinib and its active metabolite	Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.	Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15
Tmax,ss of quizartinib and its active metabolite	Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.	Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15
AUCtau,ss of quizartinib and its active metabolite	Evaluate the pharmacokinetics of quizartinib and its active metabolite, AC886 by Cmax, Tmax, AUCtau, Cmax,ss, Ctrough, Tmax,ss, AUCtau,ss.	Cycle 1: Days 1, 2, 4, 8, 11, 15, 16, 18, 22, 28; Cycle 2 and on: Days 1, 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FMS-like tyrosine kinase-3 / internal tandem duplication FLT3/ITD allelic ratio	Exploratory assessment of quizartinib-related biomarkers such as FLT3-ITD allelic ratio, PIA assessment.	Cycle 1: Days 1, 2, 8, 15
PIA assessment	Exploratory assessment of quizartinib-related biomarkers such as FLT3-ITD allelic ratio, PIA assessment.	Cycle 1: Days 1, 2, 8, 15
bone marrow findings	Exploratory analyses of tumor response to quizartinib based on bone marrow findings, absolute neutrophil count, and platelet count.	Cycle 1: Days 15, 28; Cycle 2 and on: Day 28
absolute neutrophil count	Exploratory analyses of tumor response to quizartinib based on bone marrow findings, absolute neutrophil count, and platelet count.	Cycle 1: Days 15, 28; Cycle 2 and on: Day 28
platelet count	Exploratory analyses of tumor response to quizartinib based on bone marrow findings, absolute neutrophil count, and platelet count.	Cycle 1: Days 15, 28; Cycle 2 and on: Day 28

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.

Publications and helpful links

General Publications

• Usuki K, Handa H, Choi I, Yamauchi T, Iida H, Hata T, Ohwada S, Okudaira N, Nakamura K, Sakajiri S. Safety and pharmacokinetics of quizartinib in Japanese patients with relapsed or refractory acute myeloid leukemia in a phase 1 study. Int J Hematol. 2019 Dec;110(6):654-664. doi: 10.1007/s12185-019-02709-8. Epub 2019 Jul 29.

Study record dates

Study Major Dates

• Study Start: February 1, 2016
• Primary Completion (Actual): November 13, 2018
• Study Completion (Actual): November 13, 2018

Study Registration Dates

• First Submitted: February 2, 2016
• First Submitted That Met QC Criteria: February 3, 2016
• First Posted (Estimate): February 5, 2016

Study Record Updates

• Last Update Posted (Actual): February 12, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: oncology; AML; phase 1
• Other Study ID Numbers: AC220-A-J101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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/
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes