Phase 2 Study of Quizartinib in Participants With Acute Myeloid Leukemia (AML) FLT3 Internal Tandem Duplication (FLT3/ITD) Mutation

Phase 2 Open-label, Single-arm Study of Quizartinib (AC220) Monotherapy in Japanese Patients With FLT3-ITD Positive Refractory or Relapsed Acute Myeloid Leukemia

This is a Phase 2, multi-center, open-label study to evaluate the efficacy, safety and pharmacokinetics of quizartinib monotherapy in Japanese subjects with FLT3-ITD positive refractory or relapsed acute myeloid leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: Quizartinib

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
  • Akita, Japan
  • Chiba, Japan
  • Fukui, Japan
  • Fukuoka, Japan
  • Fukushima, Japan
  • Gifu, Japan
  • Gunma, Japan
  • Hiroshima, Japan
  • Hokkaido, Japan
  • Ibaraki, Japan
  • Kagoshima, Japan
  • Kanagawa, Japan
  • Kyoto, Japan
  • Miyagi, Japan
  • Nagasaki, Japan
  • Nara, Japan
  • Okayama, Japan
  • Osaka, Japan
  • Saga, Japan
  • Saitama, Japan
  • Shizuoka, Japan
  • Tochigi, Japan
  • Tokyo, Japan
  • Toyama, Japan
  • Yamagata, Japan
  • Yamanashi, 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:

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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Initial dose 30 mg/day quizartinib; Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15.	Drug: Quizartinib; Quizartinib was orally administered once daily every morning. Treatment with quizartinib was administered in 28-day cycles and continued until the discontinuation criteria for treatment were met.
EXPERIMENTAL: Initial dose 20 mg/day quizartinib; Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15.	Drug: Quizartinib; Quizartinib was orally administered once daily every morning. Treatment with quizartinib was administered in 28-day cycles and continued until the discontinuation criteria for treatment were met.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Complete Remission (CRc) Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	The composite complete remission (CRc) rate is defined as the proportion of participants whose best response is complete remission [CR], CR with incomplete platelet recovery [CRp], or CR with incomplete hematological recovery [CRi]) after treatment with quizartinib.	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 up until the end of treatment, except for responses from any subsequent AML therapy including transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Best response is defined as the best measured response over all response assessments (complete response [CR], CR with incomplete platelet recovery [CRp], CR with incomplete hematological recovery [CRi], partial remission [PR], no response [NR], or Unknown) at all time points after the first dose of the study drug to the end of treatment (does not include response from any subsequent AML therapy including transplantation).	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML
Response Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML		Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML
Duration of Composite Complete Remission (CRc) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Duration from the date of first composite complete remission (CRc) (complete remission [CR], CR with incomplete platelet recovery [CRp], or CR with incomplete hematological recovery [CRi]) observed to the date of documented relapse was assessed.	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 up until the end of treatment, except for responses from any subsequent AML therapy including transplantation
Overall Survival (OS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	OS is defined as the time from registration (enrollment) until death from any cause.	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 1 year
Event-free Survival (EFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Event-free survival is defined as the time from date of registration until documented refractory disease, relapse after response of composite complete remission (CRc = complete remission [CR], CR with incomplete platelet recovery [CRp], or CR with incomplete hematological recovery [CRi]), or death from any cause, whichever occurs first.	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 32 weeks
Leukemia-free Survival (LFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Leukemia-free survival (LFS) is the time from the first documented response of CRc until documented relapse or death from any cause. The analysis for LFS will be conditional on the participant having a documented best response of CRc.	Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 28 weeks
Hematopoietic Stem Cell Transplantation Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML	Proportion of participants who start hematopoietic stem cell transplantation (HSCT) immediately after the end of treatment with the study drug without receiving other treatment for AML, except for conditioning regiment for HSCT, was assessed.	Up to new AML treatment or 1 year post treatment
Change in the Area Under the Plasma Concentration Time Curve (AUC) of Quizartinib and Its Active Metabolite After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML		Cycle 1, Days 1 and 15; Cycle 2, Day 1
Change in the Maximum Plasma Concentration (Cmax) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML		Cycle 1, Days 1 and 15; Cycle 2, Day 1
Change in the Trough Plasma Concentration (Ctrough) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML		Cycle 1, Day 15
Change in the Time to Reach Maximum Plasma Concentration (Tmax) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML		Cycle 1, Days 1 and 15; Cycle 2, Day 1

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.
• Collaborators: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 8, 2016
• Primary Completion (ACTUAL): March 28, 2018
• Study Completion (ACTUAL): September 14, 2018

Study Registration Dates

• First Submitted: December 5, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (ESTIMATE): December 7, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 4, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: FLT3-ITD; Positive refractory or relapsed acute myeloid leukemia; Hematology malignancy; Developmental Phase II
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: AC220-A-J201; JAPIC CTI-163441 (OTHER: JAPIC CTI)

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