Efficacy Study for AC220 to Treat Acute Myeloid Leukemia (AML) (ACE)

• ClinicalTrials.gov Identifier: NCT00989261
• Recruitment Status: Completed
• First Posted: October 5, 2009
• Results First Posted: November 29, 2019
• Last Update Posted: December 11, 2019
• Sponsor: Daiichi Sankyo
• Information provided by (Responsible Party): Daiichi Sankyo

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia
• Intervention: Drug: Compound AC220
• Enrollment: 333

Participant Flow

Recruitment Details	A total of 333 participants from 9 countries (United States, Germany, France, Italy, United Kingdom, Spain, Netherlands, Canada, and Poland) who met all inclusion and none of the exclusion criteria were included in the study.
Pre-assignment Details	All participants in both cohorts initially received a starting dose of 200 mg/day quizartinib (maximum tolerated dose). To ensure complete inhibition of FLT3, all male subjects in both cohorts later received a starting dose of 135 mg/day quizartinib, and all females received a starting dose of 90 mg/day.

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib. Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-) After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib. Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-) After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Period Title: Overall Study
Started	157	176
Completed	142	154
Not Completed	15	22
Reason Not Completed
Still in follow up	12	21
Withdrawal by Subject	0	1
Lost to Follow-up	3	0

Baseline Characteristics

Arm/Group Title		Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age	Total
Arm/Group Description		Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib. Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-) After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib. Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-) After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Total of all reporting groups
Overall Number of Baseline Participants		157	176	333
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	157 participants	176 participants	333 participants
		69.0; (32 to 86)	51.0; (19 to 77)	63.0; (19 to 86)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	157 participants	176 participants	333 participants
Less than 60 years		2 1.3%	132 75.0%	134 40.2%
At least 60 years		155 98.7%	44 25.0%	199 59.8%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	157 participants	176 participants	333 participants
	Female	80 51.0%	83 47.2%	163 48.9%
	Male	77 49.0%	93 52.8%	170 51.1%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	157 participants	176 participants	333 participants
	Hispanic or Latino	4 2.5%	6 3.4%	10 3.0%
	Not Hispanic or Latino	126 80.3%	150 85.2%	276 82.9%
	Unknown or Not Reported	27 17.2%	20 11.4%	47 14.1%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	157 participants	176 participants	333 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	2 1.3%	5 2.8%	7 2.1%
	Native Hawaiian or Other Pacific Islander	1 0.6%	0 0.0%	1 0.3%
	Black or African American	5 3.2%	5 2.8%	10 3.0%
	White	135 86.0%	156 88.6%	291 87.4%
	More than one race	2 1.3%	6 3.4%	8 2.4%
	Unknown or Not Reported	12 7.6%	4 2.3%	16 4.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	157 participants	176 participants	333 participants
Canada		2	2	4
Netherlands		5	5	10
United States		59	86	145
Poland		2	0	2
Italy		16	12	28
United Kingdom		7	7	14
France		24	29	53
Germany		37	27	64
Spain		5	8	13
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	157 participants	176 participants	333 participants
		74.66 (14.75)	74.76 (19.41)	74.72 (17.33)

Outcome Measures

1. Primary Outcome

Title	Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants)
Description	Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD[+] Participants) Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia <1 x 10^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission.
Time Frame	Within the first 3 cycles of treatment (84 days)

Outcome Measure Data

Analysis Population Description

Derived disease assessments were conducted in the Safety Population (FLT3-ITD [+] participants).

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	112	136
Measure Type: Number; Unit of Measure: participants
Composite complete remission (CRc)	63	62
Complete remission (CR)	3	5
Complete remission with incomplete platelet (CRp)	4	2
Complete remission with incomplete hematologic CRi	56	55
Partial remission (PR)	23	39
No response (NR)	20	24
Unknown	6	11

2. Primary Outcome

Title	Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants)
Description	Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD[-] Participants) Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia <1 x 10^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission.
Time Frame	Within the first 3 cycles of treatment (84 days)

Outcome Measure Data

Analysis Population Description

Derived disease assessments were conducted in the Safety Population (FLT3-ITD [-] participants).

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	44	40
Measure Type: Number; Unit of Measure: participants
Composite complete remission (CRc)	16	12
Complete remission (CR)	2	1
Complete remission with incomplete platelet (CRp)	1	1
Complete remission with incomplete hematologic CRi	13	10
Partial remission (PR)	4	6
No response (NR)	17	16
Unknown	7	6

3. Primary Outcome

Title	Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status
Description	CRc is defined as composite complete remission (CR+CRp+CRi) - CR = complete remission; CRp = complete remission with incomplete platelet recovery; CRi = complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia = all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia <1 x 10^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib = all criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion.
Time Frame	within 28 months

Outcome Measure Data

Analysis Population Description

Composite complete remission was assessed in the Safety Population.

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	157	176
Measure Type: Number; Unit of Measure: participants
FLT3-ITD(+)	63	62
FLT3-ITD(-)	16	12

4. Secondary Outcome

Title	Duration of Composite Complete Remission in FLT3-ITD (+) Participants Who Achieved CRc Based on All On-Treatment Data
Description	Kaplan-Meier analysis of duration of composite complete remission derived based on local morphology including all on-treatment data (Safety Population). The definition of relapse at CRc includes an evaluation of blasts in the peripheral blood of >1%.Though not specified in the protocol, the addition of these criteria was deemed necessary for consistency with the Cheson criteria.
Time Frame	From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment

Outcome Measure Data

Analysis Population Description

Duration of composite complete remission was assessed in the Safety Population based on FLT3-ITD (+) participants available for this analysis (Cohort 1: n=63; Cohort 2: n=62).

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	63	62
Median (95% Confidence Interval); Unit of Measure: weeks
	12.1; (6.3 to 15.7)	10.6; (8.1 to 16.1)

5. Secondary Outcome

Title	Duration of Composite Complete Remission in FLT3-ITD (-) Participants Who Achieved CRc Based on All On-Treatment Data
Description	Kaplan-Meier analysis of duration of composite complete remission derived based on local morphology including all on-treatment data (Safety Population). The definition of relapse at CRc includes an evaluation of blasts in the peripheral blood of >1%.Though not specified in the protocol, the addition of these criteria was deemed necessary for consistency with the Cheson criteria.
Time Frame	From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment

Outcome Measure Data

Analysis Population Description

Duration of composite complete remission was assessed in the Safety Population based on FLT3-ITD (-) participants available for this analysis (Cohort 1: n=16; Cohort 2: n=12).

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	16	12
Median (95% Confidence Interval); Unit of Measure: weeks
	16.4; (8.1 to 30.4)	7.0; (4.1 to 8.1)

6. Secondary Outcome

Title	Duration of Any Response in FLT3-ITD (+) Participants
Description	Kaplan-Meier analysis of duration of any response (CR, CRp, CRi, or PR), derived based on local morphology for participants who achieved a response during the first 3 cycles of treatment (Safety Population).
Time Frame	From the time of any response until disease progression or death, up to approximately 3 years post treatment

Outcome Measure Data

Analysis Population Description

Response (based on local morphology) was assessed in the Safety Population (FLT3-ITD [+] participants).

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	83	99
Median (95% Confidence Interval); Unit of Measure: weeks
	15.7; (14.1 to 21.3)	14.1; (11.1 to 22.3)

7. Secondary Outcome

Title	Duration of Any Response in FLT3-ITD (-) Participants
Description	Kaplan-Meier analysis of duration of any response (CR, CRp, CRi, or PR), derived based on local morphology for participants who achieved a response during the first 3 cycles of treatment (Safety Population).
Time Frame	From the time of any response until disease progression or death, up to approximately 3 years post treatment

Outcome Measure Data

Analysis Population Description

Response (based on local morphology) was assessed in the Safety Population (FLT3-ITD [-] participants).

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	20	18
Median (95% Confidence Interval); Unit of Measure: weeks
	22.4; (10.1 to 34.1)	8.1; (7.4 to 8.1)

8. Secondary Outcome

Title	Median Duration of Leukemia-free Survival in FLT3-ITD (+) Participants
Description	Kaplan-Meier analysis of leukemia-free survival in participants who achieved a CRc in the first three cycles of treatment derived based on local morphology (Safety Population).
Time Frame	From the time CRc was achieved until disease progression or death, up to approximately 3 years post treatment

Outcome Measure Data

Analysis Population Description

Leukemia-free survival (based on local morphology) was assessed in the Safety Population (FLT3-ITD [+] participants).

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	61	61
Median (95% Confidence Interval); Unit of Measure: weeks
	12.1; (6.1 to 14.3)	12.9; (9.4 to 19.1)

9. Secondary Outcome

Title	Median Duration of Leukemia-free Survival in FLT3-ITD (-) Participants
Description	Kaplan-Meier analysis of leukemia-free survival in participants who achieved a CRc in the first three cycles of treatment derived based on local morphology (Safety Population).
Time Frame	From the time CRc was achieved until disease progression or death, up to approximately 3 years post treatment

Outcome Measure Data

Analysis Population Description

Leukemia-free survival (based on local morphology) was assessed in the Safety Population (FLT3-ITD [-] participants).

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	14	11
Median (95% Confidence Interval); Unit of Measure: weeks
	16.4; (8.1 to 26.1)	7.0; (5.0 to 8.1)

10. Secondary Outcome

Title	Median Duration of Overall Survival in FLT3-ITD (+) Participants
Description	Kaplan-Meier analysis of overall survival (Safety Population)
Time Frame	Time from first dose to death from any cause, up to 3 years post treatment

Outcome Measure Data

Analysis Population Description

Overall survival was assessed in the Safety Population (FLT3-ITD [+] participants).

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	112	136
Median (95% Confidence Interval); Unit of Measure: weeks
	25.4; (21.3 to 29.7)	24.0; (21.1 to 27.1)

11. Secondary Outcome

Title	Median Duration of Overall Survival in FLT3-ITD (-) Participants
Description	Kaplan-Meier analysis of overall survival (Safety Population)
Time Frame	Time from first dose to death from any cause, up to approximately 3 years post treatment

Outcome Measure Data

Analysis Population Description

Overall survival was assessed in the Safety Population (FLT3-ITD [-] participants).

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	44	40
Median (95% Confidence Interval); Unit of Measure: weeks
	19.1; (12.0 to 29.4)	25.1; (18.1 to 37.0)

12. Secondary Outcome

Title	Early Treatment-related Death
Description	Early treatment-related deaths included all treatment-related deaths prior to the end of Cycle 3 with a 3-day window (Cycle 3 end date + 3 days), unless the death was following a CRc response assessed by the Investigator.
Time Frame	Within first 3 cycles of treatment (84 days)

Outcome Measure Data

Analysis Population Description

Early treatment-related deaths were assessed in the Safety Population.

Arm/Group Title	Cohort 1; ≥60 Years of Age	Cohort 2; ≥18 Years of Age
Arm/Group Description:	Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.; Exploratory (N=24): FLT3-ITD(+): n=22; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=133): FLT3-ITD(+): n=90; FLT3-ITD(-): n=42; unknown: n=1; Total (N=157): FLT3-ITD (+): n=112; FLT3-ITD(-): n=44; unknown: n=1 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.	Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.; Exploratory (N=38): FLT3-ITD(+): n=36; FLT3-ITD(-): n=2; unknown: n=0; Confirmatory (N=138): FLT3-ITD(+): n=100; FLT3-ITD(-): n=38; unknown: n=0 Total (N=176): FLT3-ITD(+): n=136; FLT3-ITD(-): n=40; unknown: n=0 After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
Overall Number of Participants Analyzed	157	176
Measure Type: Number; Unit of Measure: participants
	4	4

Adverse Events

Time Frame	Adverse event (AE) data was collected after the first dose of study drug through 30 days after the last dose of study drug, approximately 5 years.
Adverse Event Reporting Description	Of note, AML disease progression (which includes the verbatim terms of progressive disease, disease progression, and relapsed AML) is reported as an AE in the data output and in the in-text tables; however, it is not considered an AE because of the population under study and is not further discussed.
Arm/Group Title	Cohort 1; ≥60 Years of Age		Cohort 2; ≥18 Years of Age
Arm/Group Description	FLT3-ITD positive and negative populations will be divided into 2 cohorts as follows: Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission <12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib. Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-) After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.		Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib. Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-) After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day.
All-Cause Mortality
	Cohort 1; ≥60 Years of Age		Cohort 2; ≥18 Years of Age
	Affected / at Risk (%)		Affected / at Risk (%)
Total	71/157 (45.22%)		60/176 (34.09%)
Serious Adverse Events
	Cohort 1; ≥60 Years of Age		Cohort 2; ≥18 Years of Age
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/157 (85.35%)		135/176 (76.70%)
Blood and lymphatic system disorders
Anemia † 1	7/157 (4.46%)		6/176 (3.41%)
Bone marrow failure † 1	1/157 (0.64%)		1/176 (0.57%)
Disseminated intravascular coagulation † 1	0/157 (0.00%)		2/176 (1.14%)
Febrile bone marrow aplasia † 1	4/157 (2.55%)		3/176 (1.70%)
Febrile neutropenia † 1	60/157 (38.22%)		66/176 (37.50%)
Leukocytosis † 1	2/157 (1.27%)		0/176 (0.00%)
Leukopenia † 1	0/157 (0.00%)		2/176 (1.14%)
Lymphadenitis † 1	0/157 (0.00%)		1/176 (0.57%)
Neutropenia † 1	1/157 (0.64%)		2/176 (1.14%)
Pancytopenia † 1	1/157 (0.64%)		3/176 (1.70%)
Thrombocytopenia † 1	4/157 (2.55%)		6/176 (3.41%)
Cardiac disorders
Atrial fibrillation † 1	8/157 (5.10%)		3/176 (1.70%)
Cardiac arrest † 1	1/157 (0.64%)		2/176 (1.14%)
Cardiac failure † 1	3/157 (1.91%)		0/176 (0.00%)
Cardiac failure congestive † 1	1/157 (0.64%)		0/176 (0.00%)
Cardiomyopathy † 1	1/157 (0.64%)		1/176 (0.57%)
Myocardial infarction † 1	2/157 (1.27%)		0/176 (0.00%)
Myocardial ischemia † 1	1/157 (0.64%)		0/176 (0.00%)
Sinus tachycardia † 1	0/157 (0.00%)		1/176 (0.57%)
Tachycardia † 1	0/157 (0.00%)		1/176 (0.57%)
Torsade de pointes † 1	1/157 (0.64%)		0/176 (0.00%)
Ventricular tachycardia † 1	0/157 (0.00%)		1/176 (0.57%)
Gastrointestinal disorders
Abdominal pain † 1	2/157 (1.27%)		2/176 (1.14%)
Barrett's esophagus † 1	0/157 (0.00%)		1/176 (0.57%)
Colitis † 1	1/157 (0.64%)		0/176 (0.00%)
Constipation † 1	1/157 (0.64%)		0/176 (0.00%)
Dental caries † 1	1/157 (0.64%)		1/176 (0.57%)
Diarrhea † 1	3/157 (1.91%)		3/176 (1.70%)
Dyspepsia † 1	1/157 (0.64%)		0/176 (0.00%)
Dysphagia † 1	1/157 (0.64%)		0/176 (0.00%)
Fecal incontinence † 1	1/157 (0.64%)		0/176 (0.00%)
Gastric hemorrhage † 1	1/157 (0.64%)		0/176 (0.00%)
Gastritis † 1	1/157 (0.64%)		0/176 (0.00%)
Gastrointestinal hemorrhage † 1	4/157 (2.55%)		7/176 (3.98%)
Gastroesophageal reflux disease † 1	0/157 (0.00%)		2/176 (1.14%)
Gingival bleeding † 1	1/157 (0.64%)		1/176 (0.57%)
Hemorrhoids † 1	0/157 (0.00%)		1/176 (0.57%)
Ileitis † 1	0/157 (0.00%)		1/176 (0.57%)
Large intestine perforation † 1	1/157 (0.64%)		0/176 (0.00%)
Lower gastrointestinal hemorrhage † 1	1/157 (0.64%)		0/176 (0.00%)
Melena † 1	1/157 (0.64%)		0/176 (0.00%)
Mouth hemorrhage † 1	1/157 (0.64%)		0/176 (0.00%)
Nausea † 1	1/157 (0.64%)		5/176 (2.84%)
Neutropenic colitis † 1	0/157 (0.00%)		1/176 (0.57%)
Esophagitis † 1	1/157 (0.64%)		1/176 (0.57%)
Pancreatitis acute † 1	1/157 (0.64%)		0/176 (0.00%)
Proctalgia † 1	0/157 (0.00%)		2/176 (1.14%)
Rectal hemorrhage † 1	0/157 (0.00%)		2/176 (1.14%)
Stomatitis † 1	1/157 (0.64%)		2/176 (1.14%)
Upper gastrointestinal hemorrhage † 1	4/157 (2.55%)		1/176 (0.57%)
Vomiting † 1	2/157 (1.27%)		4/176 (2.27%)
General disorders
Asthenia † 1	2/157 (1.27%)		1/176 (0.57%)
Death † 1	1/157 (0.64%)		0/176 (0.00%)
Fatigue † 1	1/157 (0.64%)		2/176 (1.14%)
General physical health deterioration † 1	2/157 (1.27%)		4/176 (2.27%)
Localized edema † 1	1/157 (0.64%)		0/176 (0.00%)
Multi-organ failure † 1	0/157 (0.00%)		2/176 (1.14%)
Edema peripheral † 1	1/157 (0.64%)		1/176 (0.57%)
Pain † 1	1/157 (0.64%)		0/176 (0.00%)
Pyrexia † 1	10/157 (6.37%)		8/176 (4.55%)
Secretion discharge † 1	1/157 (0.64%)		0/176 (0.00%)
Systemic inflammatory response syndrome † 1	1/157 (0.64%)		0/176 (0.00%)
Hepatobiliary disorders
Acute hepatic failure † 1	1/157 (0.64%)		0/176 (0.00%)
Hepatic failure † 1	1/157 (0.64%)		0/176 (0.00%)
Hepatocellular injury † 1	1/157 (0.64%)		0/176 (0.00%)
Hyperbilirubinemia † 1	1/157 (0.64%)		2/176 (1.14%)
Immune system disorders
Graft versus host disease in skin † 1	0/157 (0.00%)		1/176 (0.57%)
Infections and infestations
Abscess neck † 1	0/157 (0.00%)		1/176 (0.57%)
Acinetobacter bacteremia † 1	0/157 (0.00%)		1/176 (0.57%)
Acute sinusitis † 1	0/157 (0.00%)		1/176 (0.57%)
Anal abscess † 1	0/157 (0.00%)		1/176 (0.57%)
Anorectal infection † 1	0/157 (0.00%)		1/176 (0.57%)
Arthritis bacterial † 1	1/157 (0.64%)		1/176 (0.57%)
Bacteremia † 1	6/157 (3.82%)		4/176 (2.27%)
Bacterial sepsis † 1	2/157 (1.27%)		2/176 (1.14%)
Breast cellulitis † 1	0/157 (0.00%)		1/176 (0.57%)
Bronchiolitis † 1	1/157 (0.64%)		0/176 (0.00%)
Bronchitis † 1	1/157 (0.64%)		1/176 (0.57%)
Bronchopulmonary aspergillosis † 1	2/157 (1.27%)		1/176 (0.57%)
Candidiasis † 1	0/157 (0.00%)		1/176 (0.57%)
Cellulitis † 1	5/157 (3.18%)		3/176 (1.70%)
Cellulitis orbital † 1	0/157 (0.00%)		2/176 (1.14%)
Clostridial infection † 1	0/157 (0.00%)		3/176 (1.70%)
Clostridium difficile colitis † 1	2/157 (1.27%)		1/176 (0.57%)
Cytomegalovirus infection † 1	0/157 (0.00%)		1/176 (0.57%)
Device related infection † 1	1/157 (0.64%)		4/176 (2.27%)
Enterobacter bacteremia † 1	0/157 (0.00%)		1/176 (0.57%)
Enterobacter infection † 1	0/157 (0.00%)		1/176 (0.57%)
Enterococcal infection † 1	0/157 (0.00%)		2/176 (1.14%)
Enterocolitis infectious † 1	1/157 (0.64%)		0/176 (0.00%)
Escherichia bacteremia † 1	0/157 (0.00%)		1/176 (0.57%)
Escherichia infection † 1	0/157 (0.00%)		1/176 (0.57%)
Escherichia sepsis † 1	0/157 (0.00%)		1/176 (0.57%)
Escherichia urinary tract infection † 1	1/157 (0.64%)		0/176 (0.00%)
Febrile infection † 1	1/157 (0.64%)		0/176 (0.00%)
Gastroenteritis † 1	1/157 (0.64%)		1/176 (0.57%)
Gastroenteritis viral † 1	0/157 (0.00%)		1/176 (0.57%)
Gastrointestinal infection † 1	1/157 (0.64%)		0/176 (0.00%)
Gingival infection † 1	0/157 (0.00%)		1/176 (0.57%)
Hepatic infection † 1	0/157 (0.00%)		1/176 (0.57%)
Herpes zoster † 1	1/157 (0.64%)		0/176 (0.00%)
Infection † 1	2/157 (1.27%)		1/176 (0.57%)
Influenza † 1	1/157 (0.64%)		0/176 (0.00%)
Klebsiella bacteremia † 1	0/157 (0.00%)		1/176 (0.57%)
Klebsiella infection † 1	0/157 (0.00%)		1/176 (0.57%)
Laryngitis † 1	0/157 (0.00%)		1/176 (0.57%)
Lobar pneumonia † 1	2/157 (1.27%)		1/176 (0.57%)
Lower respiratory tract infection † 1	0/157 (0.00%)		1/176 (0.57%)
Lower respiratory tract infection fungal † 1	0/157 (0.00%)		1/176 (0.57%)
Lung infection † 1	1/157 (0.64%)		6/176 (3.41%)
Lung infection pseudomonal † 1	1/157 (0.64%)		0/176 (0.00%)
Meningitis bacterial † 1	0/157 (0.00%)		1/176 (0.57%)
Mucosal infection † 1	1/157 (0.64%)		0/176 (0.00%)
Necrotizing fascitis † 1	1/157 (0.64%)		0/176 (0.00%)
Neutropenic sepsis † 1	1/157 (0.64%)		0/176 (0.00%)
Oral candidiasis † 1	1/157 (0.64%)		0/176 (0.00%)
Oral herpes † 1	1/157 (0.64%)		0/176 (0.00%)
Oral infection † 1	1/157 (0.64%)		0/176 (0.00%)
Osteomyelitis † 1	1/157 (0.64%)		0/176 (0.00%)
Parainfluenzae virus infection † 1	0/157 (0.00%)		1/176 (0.57%)
Pericoronitis † 1	0/157 (0.00%)		1/176 (0.57%)
Periodontitis † 1	1/157 (0.64%)		0/176 (0.00%)
Pharyngitis † 1	0/157 (0.00%)		2/176 (1.14%)
Pneumonia † 1	24/157 (15.29%)		16/176 (9.09%)
Pneumonia fungal † 1	1/157 (0.64%)		7/176 (3.98%)
Pneumonia pneumococcal † 1	0/157 (0.00%)		1/176 (0.57%)
Pneumonia streptococcal † 1	1/157 (0.64%)		0/176 (0.00%)
Pseudomonal bacteremia † 1	1/157 (0.64%)		0/176 (0.00%)
Pseudomonal sepsis † 1	1/157 (0.64%)		0/176 (0.00%)
Pseudomonas infection † 1	0/157 (0.00%)		1/176 (0.57%)
Rectal abscess † 1	0/157 (0.00%)		1/176 (0.57%)
Respiratory tract infection fungal † 1	0/157 (0.00%)		1/176 (0.57%)
Rhinovirus infection † 1	1/157 (0.64%)		1/176 (0.57%)
Sepsis † 1	12/157 (7.64%)		13/176 (7.39%)
Sepsis syndrome † 1	1/157 (0.64%)		0/176 (0.00%)
Septic shock † 1	3/157 (1.91%)		3/176 (1.70%)
Serratia bacteremia † 1	1/157 (0.64%)		0/176 (0.00%)
Sinusitis † 1	0/157 (0.00%)		2/176 (1.14%)
Sinusitis fungal † 1	0/157 (0.00%)		1/176 (0.57%)
Skin infection † 1	1/157 (0.64%)		1/176 (0.57%)
Soft tissue infection † 1	1/157 (0.64%)		0/176 (0.00%)
Staphylococcal bacteremia † 1	0/157 (0.00%)		2/176 (1.14%)
Staphylococcal sepsis † 1	2/157 (1.27%)		3/176 (1.70%)
Subcutaneous abscess † 1	0/157 (0.00%)		1/176 (0.57%)
Upper respiratory tract infection † 1	0/157 (0.00%)		1/176 (0.57%)
Urinary tract infection † 1	6/157 (3.82%)		6/176 (3.41%)
Urinary tract infection bacterial † 1	2/157 (1.27%)		0/176 (0.00%)
Urosepsis † 1	1/157 (0.64%)		0/176 (0.00%)
Viral upper respiratory tract infection † 1	0/157 (0.00%)		1/176 (0.57%)
Vulval abscess † 1	1/157 (0.64%)		0/176 (0.00%)
Vulval cellulitis † 1	1/157 (0.64%)		0/176 (0.00%)
Vulvitis † 1	1/157 (0.64%)		0/176 (0.00%)
Wound infection † 1	1/157 (0.64%)		0/176 (0.00%)
Injury, poisoning and procedural complications
Accidental overdose † 1	1/157 (0.64%)		1/176 (0.57%)
Accidental poisoning † 1	1/157 (0.64%)		0/176 (0.00%)
Endotracheal intubation complication † 1	1/157 (0.64%)		0/176 (0.00%)
Head injury † 1	1/157 (0.64%)		0/176 (0.00%)
Subdural hematoma † 1	3/157 (1.91%)		0/176 (0.00%)
Subdural hemorrhage † 1	1/157 (0.64%)		0/176 (0.00%)
Investigations
Alanine aminotransferase increased † 1	1/157 (0.64%)		3/176 (1.70%)
Aspartate aminotransferase increased † 1	0/157 (0.00%)		1/176 (0.57%)
Blood bilirubin increased † 1	1/157 (0.64%)		4/176 (2.27%)
Blood potassium decreased † 1	1/157 (0.64%)		0/176 (0.00%)
C-reactive protein increased † 1	1/157 (0.64%)		0/176 (0.00%)
Ejection fraction decreased † 1	0/157 (0.00%)		1/176 (0.57%)
Electrocardiogram QT prolonged † 1	17/157 (10.83%)		16/176 (9.09%)
Hepatic enzyme increased † 1	1/157 (0.64%)		0/176 (0.00%)
Troponin T increased † 1	1/157 (0.64%)		0/176 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	1/157 (0.64%)		2/176 (1.14%)
Dehydration † 1	5/157 (3.18%)		2/176 (1.14%)
Hypernatremia † 1	0/157 (0.00%)		1/176 (0.57%)
Hypocalcemia † 1	0/157 (0.00%)		2/176 (1.14%)
Hypoglycemia † 1	0/157 (0.00%)		1/176 (0.57%)
Hypokalemia † 1	0/157 (0.00%)		2/176 (1.14%)
Hyponatremia † 1	1/157 (0.64%)		1/176 (0.57%)
Tumor lysis syndrome † 1	0/157 (0.00%)		1/176 (0.57%)
Type 1 diabetes mellitus † 1	1/157 (0.64%)		0/176 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/157 (0.00%)		1/176 (0.57%)
Arthritis † 1	0/157 (0.00%)		2/176 (1.14%)
Back pain † 1	1/157 (0.64%)		0/176 (0.00%)
Bursitis † 1	0/157 (0.00%)		1/176 (0.57%)
Joint effusion † 1	1/157 (0.64%)		0/176 (0.00%)
Muscle hemorrhage † 1	0/157 (0.00%)		1/176 (0.57%)
Musculoskeletal pain † 1	0/157 (0.00%)		1/176 (0.57%)
Myalgia † 1	0/157 (0.00%)		1/176 (0.57%)
Neck pain † 1	2/157 (1.27%)		0/176 (0.00%)
Pain in extremity † 1	1/157 (0.64%)		0/176 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukemia † 1	37/157 (23.57%)		36/176 (20.45%)
Leukemic infiltration brain † 1	0/157 (0.00%)		1/176 (0.57%)
Lymphohistiocytosis † 1	1/157 (0.64%)		0/176 (0.00%)
Myelofibrosis † 1	1/157 (0.64%)		0/176 (0.00%)
Non-Hodgkin's lymphoma † 1	1/157 (0.64%)		0/176 (0.00%)
Tumor pain † 1	0/157 (0.00%)		1/176 (0.57%)
Nervous system disorders
Aphasia † 1	1/157 (0.64%)		0/176 (0.00%)
Central nervous system lesion † 1	1/157 (0.64%)		0/176 (0.00%)
Cerebral hemorrhage † 1	2/157 (1.27%)		1/176 (0.57%)
Cerebrovascular accident † 1	0/157 (0.00%)		3/176 (1.70%)
Cognitive disorder † 1	1/157 (0.64%)		0/176 (0.00%)
Coma † 1	1/157 (0.64%)		0/176 (0.00%)
Convulsion † 1	1/157 (0.64%)		1/176 (0.57%)
Dizziness † 1	1/157 (0.64%)		0/176 (0.00%)
Encephalitis † 1	1/157 (0.64%)		0/176 (0.00%)
Hemorrhage intracranial † 1	4/157 (2.55%)		1/176 (0.57%)
Hemorrhagic stroke † 1	1/157 (0.64%)		0/176 (0.00%)
Headache † 1	2/157 (1.27%)		1/176 (0.57%)
Intraventricular hemorrhage † 1	0/157 (0.00%)		1/176 (0.57%)
Memory impairment † 1	1/157 (0.64%)		0/176 (0.00%)
Postictal state † 1	1/157 (0.64%)		0/176 (0.00%)
Somnolence † 1	0/157 (0.00%)		2/176 (1.14%)
Subarachnoid hemorrhage † 1	0/157 (0.00%)		1/176 (0.57%)
Syncope † 1	1/157 (0.64%)		1/176 (0.57%)
Transient ischemic attack † 1	2/157 (1.27%)		0/176 (0.00%)
Psychiatric disorders
Anxiety † 1	1/157 (0.64%)		0/176 (0.00%)
Confusional state † 1	1/157 (0.64%)		0/176 (0.00%)
Delirium † 1	0/157 (0.00%)		1/176 (0.57%)
Mental status changes † 1	3/157 (1.91%)		1/176 (0.57%)
Renal and urinary disorders
Hematuria † 1	1/157 (0.64%)		0/176 (0.00%)
Nephrolithiasis † 1	1/157 (0.64%)		0/176 (0.00%)
Renal failure † 1	3/157 (1.91%)		0/176 (0.00%)
Renal failure acute † 1	2/157 (1.27%)		1/176 (0.57%)
Renal tubular disorder † 1	0/157 (0.00%)		1/176 (0.57%)
Urinary incontinence † 1	1/157 (0.64%)		0/176 (0.00%)
Urinary retention † 1	0/157 (0.00%)		1/176 (0.57%)
Reproductive system and breast disorders
Vaginal hemorrhage † 1	0/157 (0.00%)		1/176 (0.57%)
Respiratory, thoracic and mediastinal disorders
Acute promyelocytic leukemia † 1	1/157 (0.64%)		0/176 (0.00%)
Acute respiratory failure † 1	0/157 (0.00%)		1/176 (0.57%)
Epistaxis † 1	1/157 (0.64%)		3/176 (1.70%)
Hemoptysis † 1	1/157 (0.64%)		0/176 (0.00%)
Hiccups † 1	0/157 (0.00%)		1/176 (0.57%)
Pleural effusion † 1	2/157 (1.27%)		0/176 (0.00%)
Pneumonia aspiration † 1	1/157 (0.64%)		0/176 (0.00%)
Pneumonitis † 1	1/157 (0.64%)		0/176 (0.00%)
Pulmonary alveolar hemorrhage † 1	0/157 (0.00%)		1/176 (0.57%)
Pulmonary embolism † 1	0/157 (0.00%)		1/176 (0.57%)
Pulmonary edema † 1	1/157 (0.64%)		0/176 (0.00%)
Respiratory arrest † 1	1/157 (0.64%)		0/176 (0.00%)
Respiratory distress † 1	1/157 (0.64%)		0/176 (0.00%)
Respiratory failure † 1	2/157 (1.27%)		2/176 (1.14%)
Skin and subcutaneous tissue disorders
Acute febrile neutrophilic dermatosis † 1	1/157 (0.64%)		3/176 (1.70%)
Petechiae † 1	0/157 (0.00%)		1/176 (0.57%)
Rash † 1	1/157 (0.64%)		1/176 (0.57%)
Toxic skin eruption † 1	0/157 (0.00%)		1/176 (0.57%)
Vascular disorders
Hematoma † 1	1/157 (0.64%)		3/176 (1.70%)
Hemorrhage † 1	0/157 (0.00%)		1/176 (0.57%)
Hypotension † 1	3/157 (1.91%)		0/176 (0.00%)
1 Term from vocabulary, MedDRA 15.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cohort 1; ≥60 Years of Age		Cohort 2; ≥18 Years of Age
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	151/157 (96.18%)		175/176 (99.43%)
Blood and lymphatic system disorders
Anemia † 1	44/157 (28.03%)	44	48/176 (27.27%)	48
Febrile neutropenia † 1	12/157 (7.64%)	12	14/176 (7.95%)	14
Leukopenia † 1	10/157 (6.37%)	10	18/176 (10.23%)	18
Neutropenia † 1	15/157 (9.55%)	15	20/176 (11.36%)	20
Pancytopenia † 1	9/157 (5.73%)	9	2/176 (1.14%)	2
Thrombocytopenia † 1	22/157 (14.01%)	22	25/176 (14.20%)	25
Cardiac disorders
Tachycardia † 1	10/157 (6.37%)	10	10/176 (5.68%)	10
Gastrointestinal disorders
Abdominal pain † 1	19/157 (12.10%)	19	23/176 (13.07%)	23
Abdominal pain upper † 1	24/157 (15.29%)	24	3/176 (1.70%)	3
Constipation † 1	35/157 (22.29%)	35	36/176 (20.45%)	36
Diarrhea † 1	65/157 (41.40%)	65	67/176 (38.07%)	67
Dry mouth † 1	8/157 (5.10%)	8	2/176 (1.14%)	2
Dyspepsia † 1	29/157 (18.47%)	29	25/176 (14.20%)	25
Gastroesophageal reflux disease † 1	16/157 (10.19%)	16	9/176 (5.11%)	9
Gingival bleeding † 1	6/157 (3.82%)	6	9/176 (5.11%)	9
Hemorrhoids † 1	10/157 (6.37%)	10	9/176 (5.11%)	9
Mouth hemorrhage † 1	12/157 (7.64%)	12	10/176 (5.68%)	10
Nausea † 1	85/157 (54.14%)	85	89/176 (50.57%)	89
Stomatitis † 1	9/157 (5.73%)	9	7/176 (3.98%)	7
Vomiting † 1	57/157 (36.31%)	57	70/176 (39.77%)	70
General disorders
Asthenia † 1	33/157 (21.02%)	33	32/176 (18.18%)	32
Chest pain † 1	10/157 (6.37%)	10	13/176 (7.39%)	13
Chills † 1	13/157 (8.28%)	13	14/176 (7.95%)	14
Fatigue † 1	62/157 (39.49%)	62	49/176 (27.84%)	49
Mucosal inflammation † 1	8/157 (5.10%)	8	15/176 (8.52%)	15
Edema peripheral † 1	46/157 (29.30%)	46	45/176 (25.57%)	45
Pyrexia † 1	47/157 (29.94%)	47	49/176 (27.84%)	49
Infections and infestations
Oral candidiasis † 1	9/157 (5.73%)	9	10/176 (5.68%)	10
Oral herpes † 1	12/157 (7.64%)	12	9/176 (5.11%)	9
Pneumonia † 1	2/157 (1.27%)	2	15/176 (8.52%)	15
Sinusitis † 1	3/157 (1.91%)	3	9/176 (5.11%)	9
Urinary tract infection † 1	9/157 (5.73%)	9	8/176 (4.55%)	8
Injury, poisoning and procedural complications
Contusion † 1	14/157 (8.92%)	14	6/176 (3.41%)	6
Investigations
Alanine aminotransferse increased † 1	9/157 (5.73%)	9	15/176 (8.52%)	15
Aspartate aminotransferase increased † 1	8/157 (5.10%)	8	7/176 (3.98%)	7
Electrocardiogram QT prolonged † 1	31/157 (19.75%)	31	48/176 (27.27%)	48
Neutrophil count decreased † 1	8/157 (5.10%)	8	6/176 (3.41%)	6
Platelet count decreased † 1	17/157 (10.83%)	17	12/176 (6.82%)	12
Weight decreased † 1	10/157 (6.37%)	10	11/176 (6.25%)	11
Metabolism and nutrition disorders
Decreased appetite † 1	46/157 (29.30%)	46	43/176 (24.43%)	43
Hyperglycemia † 1	13/157 (8.28%)	13	11/176 (6.25%)	11
Hypocalcemia † 1	15/157 (9.55%)	15	18/176 (10.23%)	18
Hypokalemia † 1	27/157 (17.20%)	27	33/176 (18.75%)	33
Hypomagnesemia † 1	17/157 (10.83%)	17	19/176 (10.80%)	19
Hyponatremia † 1	7/157 (4.46%)	7	9/176 (5.11%)	9
Musculoskeletal and connective tissue disorders
Arthralgia † 1	14/157 (8.92%)	14	8/176 (4.55%)	8
Back pain † 1	19/157 (12.10%)	19	17/176 (9.66%)	17
Bone pain † 1	11/157 (7.01%)	11	4/176 (2.27%)	4
Muscle spasms † 1	16/157 (10.19%)	16	10/176 (5.68%)	10
Musculoskeletal pain † 1	12/157 (7.64%)	12	12/176 (6.82%)	12
Myalgia † 1	7/157 (4.46%)	7	14/176 (7.95%)	14
Neck pain † 1	10/157 (6.37%)	10	4/176 (2.27%)	4
Pain in extremity † 1	17/157 (10.83%)	17	22/176 (12.50%)	22
Nervous system disorders
Dizziness † 1	27/157 (17.20%)	27	18/176 (10.23%)	18
Dysgeusia † 1	44/157 (28.03%)	44	34/176 (19.32%)	34
Headache † 1	19/157 (12.10%)	19	24/176 (13.64%)	24
Paresthesia † 1	13/157 (8.28%)	13	5/176 (2.84%)	5
Tremor † 1	10/157 (6.37%)	10	2/176 (1.14%)	2
Psychiatric disorders
Confusional state † 1	8/157 (5.10%)	8	2/176 (1.14%)	2
Depression † 1	12/157 (7.64%)	12	10/176 (5.68%)	10
Insomnia † 1	11/157 (7.01%)	11	15/176 (8.52%)	15
Renal and urinary disorders
Hematuria † 1	10/157 (6.37%)	10	9/176 (5.11%)	9
Respiratory, thoracic and mediastinal disorders
Cough † 1	26/157 (16.56%)	26	37/176 (21.02%)	37
Dyspnea † 1	28/157 (17.83%)	28	26/176 (14.77%)	26
Dyspnea exertional † 1	8/157 (5.10%)	8	2/176 (1.14%)	2
Epistaxis † 1	29/157 (18.47%)	29	27/176 (15.34%)	27
Oropharyngeal pain † 1	8/157 (5.10%)	8	10/176 (5.68%)	10
Pleural effusion † 1	8/157 (5.10%)	8	12/176 (6.82%)	12
Skin and subcutaneous tissue disorders
Dry skin † 1	8/157 (5.10%)	8	9/176 (5.11%)	9
Erythema † 1	11/157 (7.01%)	11	14/176 (7.95%)	14
Hair color changes † 1	3/157 (1.91%)	3	9/176 (5.11%)	9
Petechiae † 1	32/157 (20.38%)	32	29/176 (16.48%)	29
Pruritus † 1	8/157 (5.10%)	8	9/176 (5.11%)	9
Rash † 1	22/157 (14.01%)	22	24/176 (13.64%)	24
Skin lesion † 1	7/157 (4.46%)	7	12/176 (6.82%)	12
Vascular disorders
Hematoma † 1	17/157 (10.83%)	17	12/176 (6.82%)	12
Hypotension † 1	17/157 (10.83%)	17	13/176 (7.39%)	13
1 Term from vocabulary, MedDRA 15.0; † Indicates events were collected by systematic assessment

Limitations and 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.

Results Point of Contact

• Name/Title: Daiichi Sankyo
• Organization: Contact for Clinical Trial Information
• Phone: 1-908-992-6400
• EMail: CTRinfo@dsi.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cortes J, Perl AE, Dohner H, Kantarjian H, Martinelli G, Kovacsovics T, Rousselot P, Steffen B, Dombret H, Estey E, Strickland S, Altman JK, Baldus CD, Burnett A, Kramer A, Russell N, Shah NP, Smith CC, Wang ES, Ifrah N, Gammon G, Trone D, Lazzaretto D, Levis M. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):889-903. doi: 10.1016/S1470-2045(18)30240-7. Epub 2018 May 31.

• Responsible Party: Daiichi Sankyo
• ClinicalTrials.gov Identifier: NCT00989261
• Other Study ID Numbers: AC220-002; 2009-013093-41 ( EudraCT Number )
• First Submitted: October 1, 2009
• First Posted: October 5, 2009
• Results First Submitted: September 25, 2019
• Results First Posted: November 29, 2019
• Last Update Posted: December 11, 2019