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

• Sponsor: Daiichi Sankyo Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02984995
• Collaborator: Daiichi Sankyo, Inc. (Industry)
• Enrollment: 37
• Locations: 27
• Arms: 2
• Actual Duration (Months): 21.2
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute	Drug: Quizartinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Open-label, Single-arm Study of Quizartinib (AC220) Monotherapy in Japanese Patients With FLT3-ITD Positive Refractory or Relapsed Acute Myeloid Leukemia
• Actual Study Start Date: Dec 8, 2016
• Actual Primary Completion Date: Mar 28, 2018
• Actual Study Completion Date: Sep 14, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Composite Complete Remission (CRc) 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 up until the end of treatment, except for responses from any subsequent AML therapy including transplantation]

   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.

Secondary Outcome Measures

1. Best Response 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]

   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).

2. 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]

3. Duration of Composite Complete Remission (CRc) 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 up until the end of treatment, except for responses from any subsequent AML therapy including transplantation]

   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.

4. Overall Survival (OS) 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 therapy including transplantation up to 1 year]

   OS is defined as the time from registration (enrollment) until death from any cause.

5. Event-free Survival (EFS) 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 therapy including transplantation up to 32 weeks]

   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.

6. Leukemia-free Survival (LFS) 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 therapy including transplantation up to 28 weeks]

   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.

7. Hematopoietic Stem Cell Transplantation Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML [Up to new AML treatment or 1 year post treatment]

   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.

8. 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]

9. 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]

10. 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]

11. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Aichi		Japan
2		Akita		Japan
3		Chiba		Japan
4		Fukui		Japan
5		Fukuoka		Japan
6		Fukushima		Japan
7		Gifu		Japan
8		Gunma		Japan
9		Hiroshima		Japan
10		Hokkaido		Japan
11		Ibaraki		Japan
12		Kagoshima		Japan
13		Kanagawa		Japan
14		Kyoto		Japan
15		Miyagi		Japan
16		Nagasaki		Japan
17		Nara		Japan
18		Okayama		Japan
19		Osaka		Japan
20		Saga		Japan
21		Saitama		Japan
22		Shizuoka		Japan
23		Tochigi		Japan
24		Tokyo		Japan
25		Toyama		Japan
26		Yamagata		Japan
27		Yamanashi		Japan

Sponsors and Collaborators

• Daiichi Sankyo Co., Ltd.
• Daiichi Sankyo, Inc.

Investigators

• Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 19, 2017

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02984995
• Other Study ID Numbers: AC220-A-J201; JAPIC CTI-163441
• First Posted: Dec 7, 2016
• Last Update Posted: Feb 17, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by Daiichi Sankyo Co., Ltd.: FLT3-ITD; Positive refractory or relapsed acute myeloid leukemia; Hematology malignancy; Developmental Phase II
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute

Study Results

Participant Flow

Recruitment Details	A total of 37 participants who met all inclusion and no exclusion criteria were enrolled in the study.
Pre-assignment Detail	Quizartinib initial dose was 30 mg/day and escalated to 60 mg/day. For subjects receiving strong cytochrome P450 (CYP) 3A4 inhibitors, the initial dose was 20 mg/day. An increase from the initial dose of 30 mg/day to 60 mg/day or 20 mg/day to 30 mg/day was determined on Day 16 of Cycle 1 and Day 1 of Cycle 2 based on dose increase criteria.

Arm/Group Title	Initial Dose 30 mg/Day Quizartinib	Initial Dose 20 mg/Day Quizartinib
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	34	3
COMPLETED	9	0
NOT COMPLETED	25	3

Baseline Characteristics

Arm/Group Title	Initial Dose 30 mg/Day Quizartinib	Initial Dose 20 mg/Day Quizartinib	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	34	3	37
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 44.1%	2 66.7%	17 45.9%
>=65 years	19 55.9%	1 33.3%	20 54.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.2 (14.51)	58.0 (9.92)	60.0 (14.68)
Sex: Female, Male (Count of Participants)
Female	22 64.7%	0 0%	22 59.5%
Male	12 35.3%	3 100%	15 40.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	34 100%	3 100%	37 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Japan	34 100%	3 100%	37 100%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	20.72 (2.53)	22.25 (3.37)	20.84 (2.58)
FLT3-ITD Status (Count of Participants)
Positive	29 85.3%	3 100%	32 86.5%
Negative	5 14.7%	0 0%	5 13.5%
Response to Prior Therapy (Count of Participants)
Relapse	21 61.8%	3 100%	24 64.9%
Refractory	13 38.2%	0 0%	13 35.1%

Outcome Measures

1. Primary Outcome

Title	Composite Complete Remission (CRc) Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

All participants with FLT3-ITD positive relapsed or refractory AML who achieved CR, CRp, or CRi, discontinued the study treatment, or completed response assessment at Cycle 4 Day 1.

Arm/Group Title	Initial Dose 30 mg/Day Quizartinib	Initial Dose 20 mg/Day Quizartinib	Total
Arm/Group Description	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.	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.	All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Measure Participants	23	3	26
Number (90% Confidence Interval) [percentage of participants]	56.5 166.2%	33.3 1110%	53.8 145.4%

2. Secondary Outcome

Title	Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Description	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).
Time Frame	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

Outcome Measure Data

Analysis Population Description

All participants with FLT3-ITD positive relapsed or refractory AML who achieved CR, CRp, CRi, or PR, discontinued the study treatment, or completed response assessment at Cycle 4 Day 1.

Arm/Group Title	Initial Dose 30 mg/Day Quizartinib	Initial Dose 20 mg/Day Quizartinib	Total
Arm/Group Description	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.	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.	All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Measure Participants	24	3	27
Complete response (CR)	0 0%	0 0%	0 0%
Complete response with incomplete platelet (CRp)	1 2.9%	0 0%	1 2.7%
Complete response with incomplete hematologic(CRi)	12 35.3%	1 33.3%	13 35.1%
Partial remission (PR)	6 17.6%	1 33.3%	7 18.9%
No response (NR)	5 14.7%	1 33.3%	6 16.2%

3. Secondary Outcome

Title	Response Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Time Frame	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

Outcome Measure Data

Analysis Population Description

All participants with FLT3-ITD positive relapsed or refractory AML who achieved CR, CRp, CRi, or PR, discontinued the study treatment, or completed response assessment at Cycle 4 Day 1.

Arm/Group Title	Initial Dose 30 mg/Day Quizartinib	Initial Dose 20 mg/Day Quizartinib	Total
Arm/Group Description	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.	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.	All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Measure Participants	24	3	27
Number (95% Confidence Interval) [percentage of participants]	79.2 232.9%	66.7 2223.3%	77.8 210.3%

4. Secondary Outcome

Title	Duration of Composite Complete Remission (CRc) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

All participants with FLT3-ITD positive relapsed or refractory AML who had a documented best response of CRc.

Arm/Group Title	Initial Dose 30 mg/Day Quizartinib	Initial Dose 20 mg/Day Quizartinib	Total
Arm/Group Description	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.	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.	All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Measure Participants	13	1	14
Median (95% Confidence Interval) [weeks]	16.1	NA	16.1

5. Secondary Outcome

Title	Overall Survival (OS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Description	OS is defined as the time from registration (enrollment) until death from any cause.
Time Frame	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

Outcome Measure Data

Analysis Population Description

All participants with FLT3-ITD positive relapsed or refractory AML.

Arm/Group Title	Initial Dose 30 mg/Day Quizartinib	Initial Dose 20 mg/Day Quizartinib	Total
Arm/Group Description	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.	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.	All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Measure Participants	29	3	32
Median (95% Confidence Interval) [weeks]	34.1	NA	34.1

6. Secondary Outcome

Title	Event-free Survival (EFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

All participants with FLT3-ITD positive relapsed or refractory AML.

Arm/Group Title	Initial Dose 30 mg/Day Quizartinib	Initial Dose 20 mg/Day Quizartinib	Total
Arm/Group Description	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.	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.	All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Measure Participants	29	3	32
Median (95% Confidence Interval) [weeks]	12.7	0.1	12.7

7. Secondary Outcome

Title	Leukemia-free Survival (LFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

All participants with FLT3-ITD positive relapsed or refractory AML and documented best response of CRc.

Arm/Group Title	Initial Dose 30 mg/Day Quizartinib	Initial Dose 20 mg/Day Quizartinib	Total
Arm/Group Description	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.	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.	All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Measure Participants	29	3	32
Median (95% Confidence Interval) [weeks]	16.1	NA	16.1

8. Secondary Outcome

Title	Hematopoietic Stem Cell Transplantation Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Description	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.
Time Frame	Up to new AML treatment or 1 year post treatment

Outcome Measure Data

Analysis Population Description

All participants with FLT3-ITD positive relapsed or refractory AML who underwent HSCT after treatment.

Arm/Group Title	Initial Dose 30 mg/Day Quizartinib	Initial Dose 20 mg/Day Quizartinib	Total
Arm/Group Description	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.	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.	All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Measure Participants	29	3	32
Number (95% Confidence Interval) [Percentage of participants]	37.9 111.5%	33.3 1110%	37.5 101.4%

9. Secondary Outcome

Title	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
Time Frame	Cycle 1, Days 1 and 15; Cycle 2, Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.

Arm/Group Title	Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)	Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)	Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor)	Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)
Arm/Group Description	Patients who received a CYP3A4 strong inhibitor received quizartinib 20 mg/day and escalated to 30 mg/day at Day 15.	Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 30 mg/day.	Patients who received a CYP3A4 strong inhibitor received quizartinib 30 mg/day.	Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 60 mg/day.
Measure Participants	3	34	2	21
Cycle 1, Day 1; Quizartinib (n=3,34,0,0)	877 (489)	1170 (716)
Cycle 1, Day 1; Active Metabolite (n=3,34,0,0)	75.1 (80.6)	560 (391)
Cycle 1, Day 15; Quizartinib (n=3,32,0,0)	2610 (693)	3970 (2610)
Cycle 1, Day 15; Active Metabolite (n=3,32,0,0)	430 (276)	3120 (1300)
Cycle 2, Day 1; Quizartinib (n=0,0,2,21)	2960 (749)	9240 (6090)
Cycle 2, Day 1; Active Metabolite (n=0,0,2,21)	983 (389)	6530 (2630)

10. Secondary Outcome

Title	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
Time Frame	Cycle 1, Days 1 and 15; Cycle 2, Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.

Arm/Group Title	Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)	Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)	Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor)	Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)
Arm/Group Description	Patients who received a CYP3A4 strong inhibitor received quizartinib 20 mg/day and escalated to 30 mg/day at Day 15.	Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 30 mg/day.	Patients who received a CYP3A4 strong inhibitor received quizartinib 30 mg/day.	Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 60 mg/day.
Measure Participants	3	34	2	21
Cycle 1, Day 1; Quizartinib (n=3,34,0,0)	48.1 (25.9)	76.9 (46.8)
Cycle 1, Day 1; Active Metabolite (n=3,34,0,0)	3.92 (4.49)	29.1 (20.9)
Cycle 1, Day 15; Quizartinib (n=3,32,0,0)	127 (35.9)	211 (132)
Cycle 1, Day 15; Active Metabolite (n=3,32,0,0)	18.9 (12.1)	146 (60.4)
Cycle 2, Day 1; Quizartinib (n=0,0,2,21)	149 (38.2)	480 (296)
Cycle 2, Day 1; Active Metabolite (n=0,0,2,21)	43.7 (17.7)	298 (118)

11. Secondary Outcome

Title	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
Time Frame	Cycle 1, Day 15

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.

Arm/Group Title	Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)	Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)	Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor)	Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)
Arm/Group Description	Patients who received a CYP3A4 strong inhibitor received quizartinib 20 mg/day and escalated to 30 mg/day at Day 15.	Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 30 mg/day.	Patients who received a CYP3A4 strong inhibitor received quizartinib 30 mg/day.	Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 60 mg/day.
Measure Participants	3	32	0	0
Cycle 1, Day 15; Quizartinib	98.2 (19.7)	128 (92.5)
Cycle 1, Day 15; Active Metabolite	17.8 (11.3)	112 (47.9)

12. Secondary Outcome

Title	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
Time Frame	Cycle 1, Days 1 and 15; Cycle 2, Day 1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.

Arm/Group Title	Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor)	Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor)	Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor)	Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)
Arm/Group Description	Patients who received a CYP3A4 strong inhibitor received quizartinib 20 mg/day and escalated to 30 mg/day at Day 15.	Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 30 mg/day.	Patients who received a CYP3A4 strong inhibitor received quizartinib 30 mg/day.	Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 60 mg/day.
Measure Participants	3	34	2	21
Cycle 1, Day 1; Quizartinib (n=3,34,0,0)	4.08	4.03
Cycle 1, Day 1; Active Metabolite (n=2,33,0,0)	24.33	24.32
Cycle 1, Day 15; Quizartinib (n=3,32,0,0)	4.08	3.06
Cycle 1, Day 15; Active Metabolite (n=3,32,0,0)	4.08	5.82
Cycle 2, Day 1; Quizartinib (n=0,0,2,21)	6.17	3.87
Cycle 2, Day 1; Active Metabolite (n=0,0,2,21)	14.17	5.65

Adverse Events

Time Frame	Adverse events were collected from the signing of the informed consent form through 45 days after last dose of study drug up to approximately 2 years.
Adverse Event Reporting Description	Adverse events that emerge (or worsen) from the first dose of study drug to the follow-up visit, 45 days after the last dose of study drug, or start date of new AML post treatment.
Arm/Group Title	Initial Dose 30 mg/Day Quizartinib		Initial 20 mg/Day Quizartinib		Total
Arm/Group Description	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.		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.		All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
All Cause Mortality
	Initial Dose 30 mg/Day Quizartinib		Initial 20 mg/Day Quizartinib		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/34 (38.2%)		1/3 (33.3%)		14/37 (37.8%)
Serious Adverse Events
	Initial Dose 30 mg/Day Quizartinib		Initial 20 mg/Day Quizartinib		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/34 (41.2%)		3/3 (100%)		17/37 (45.9%)
Blood and lymphatic system disorders
Febrile neutropenia	4/34 (11.8%)		2/3 (66.7%)		6/37 (16.2%)
Anemia	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Disseminated intravascular coagulation	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Neutropenia	0/34 (0%)		1/3 (33.3%)		1/37 (2.7%)
Gastrointestinal disorders
Vomiting	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
General disorders
Disease progression	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Non-cardiac chest pain	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Edema peripheral	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Infections and infestations
Bacteremia	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Sepsis	1/34 (2.9%)		1/3 (33.3%)		2/37 (5.4%)
Cellulitis	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Encephalitis	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Pneumonia	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Investigations
Platelet count decreased	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Respiratory, thoracic and mediastinal disorders
Hemoptysis	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Organizing pneumonia	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Pleural effusion	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Pneumonitis	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Pneumothorax	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Skin and subcutaneous tissue disorders
Pyoderma gangrenosum	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Vascular disorders
Hematoma	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Shock hemorrhagic	1/34 (2.9%)		0/3 (0%)		1/37 (2.7%)
Other (Not Including Serious) Adverse Events
	Initial Dose 30 mg/Day Quizartinib		Initial 20 mg/Day Quizartinib		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/34 (100%)		3/3 (100%)		37/37 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	10/34 (29.4%)		0/3 (0%)		10/37 (27%)
Anemia	8/34 (23.5%)		1/3 (33.3%)		9/37 (24.3%)
Thrombocytopenia	3/34 (8.8%)		1/3 (33.3%)		4/37 (10.8%)
Neutropenia	1/34 (2.9%)		1/3 (33.3%)		2/37 (5.4%)
Gastrointestinal disorders
Nausea	9/34 (26.5%)		2/3 (66.7%)		11/37 (29.7%)
Vomiting	6/34 (17.6%)		0/3 (0%)		6/37 (16.2%)
Diarrhea	4/34 (11.8%)		0/3 (0%)		4/37 (10.8%)
Constipation	2/34 (5.9%)		1/3 (33.3%)		3/37 (8.1%)
Stomatitis	3/34 (8.8%)		0/3 (0%)		3/37 (8.1%)
Proctalgia	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
General disorders
Pyrexia	4/34 (11.8%)		1/3 (33.3%)		5/37 (13.5%)
Edema	2/34 (5.9%)		1/3 (33.3%)		3/37 (8.1%)
Malaise	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Edema peripheral	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Hepatobiliary disorders
Liver disorder	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Infections and infestations
Acarodermatitis	3/34 (8.8%)		0/3 (0%)		3/37 (8.1%)
Pneumonia	3/34 (8.8%)		0/3 (0%)		3/37 (8.1%)
Bacteremia	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Cellulitis	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Device-related infections	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Injury, poisoning and procedural complications
Fall	2/34 (5.9%)		1/3 (33.3%)		3/37 (8.1%)
Transfusion reaction	0/34 (0%)		2/3 (66.7%)		2/37 (5.4%)
Investigations
Electrocardiogram QT prolonged	12/34 (35.3%)		1/3 (33.3%)		13/37 (35.1%)
Platelet count decreased	13/34 (38.2%)		0/3 (0%)		13/37 (35.1%)
Neutrophil count decreased	8/34 (23.5%)		0/3 (0%)		8/37 (21.6%)
White blood cell count decreased	8/34 (23.5%)		0/3 (0%)		8/37 (21.6%)
Alanine aminotransferase increased	4/34 (11.8%)		0/3 (0%)		4/37 (10.8%)
Gamma-glutamyltransferase increased	3/34 (8.8%)		0/3 (0%)		3/37 (8.1%)
Liver function test increased	3/34 (8.8%)		0/3 (0%)		3/37 (8.1%)
Aspartate aminotransferase increased	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Blood uric acid increased	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Metabolism and nutrition disorders
Decreased appetite	4/34 (11.8%)		1/3 (33.3%)		5/37 (13.5%)
Hypokalemia	4/34 (11.8%)		0/3 (0%)		4/37 (10.8%)
Musculoskeletal and connective tissue disorders
Back pain	3/34 (8.8%)		1/3 (33.3%)		4/37 (10.8%)
Neck pain	3/34 (8.8%)		0/3 (0%)		3/37 (8.1%)
Nervous system disorders
Headache	4/34 (11.8%)		0/3 (0%)		4/37 (10.8%)
Dysgeusia	3/34 (8.8%)		0/3 (0%)		3/37 (8.1%)
Peripheral sensory neuropathy	3/34 (8.8%)		0/3 (0%)		3/37 (8.1%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Skin and subcutaneous tissue disorders
Rash	3/34 (8.8%)		1/3 (33.3%)		4/37 (10.8%)
Urticaria	3/34 (8.8%)		0/3 (0%)		3/37 (8.1%)
Pruritus	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Rash maculo-papular	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)
Vascular disorders
Hypotension	1/34 (2.9%)		1/3 (33.3%)		2/37 (5.4%)
Phlebitis	2/34 (5.9%)		0/3 (0%)		2/37 (5.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.