Trial Outcomes & Findings for Efficacy Study for AC220 to Treat Acute Myeloid Leukemia (AML) (NCT NCT00989261)

Last Updated: 2019-12-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

333 participants

Primary outcome timeframe

Within the first 3 cycles of treatment (84 days)

Results posted on

2019-12-11

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Cohort 1; ≥60 Years of Age 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.	Cohort 2; ≥18 Years of Age 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.
Overall Study STARTED	157	176
Overall Study COMPLETED	142	154
Overall Study NOT COMPLETED	15	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1; ≥60 Years of Age 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.	Cohort 2; ≥18 Years of Age 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.
Overall Study Still in follow up	12	21
Overall Study Withdrawal by Subject	0	1
Overall Study Lost to Follow-up	3	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1; ≥60 Years of Age n=157 Participants 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.	Cohort 2; ≥18 Years of Age n=176 Participants 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 n=333 Participants Total of all reporting groups
Age, Continuous	69.0 years n=5 Participants	51.0 years n=7 Participants	63.0 years n=5 Participants
Age, Customized Less than 60 years	2 Participants n=5 Participants	132 Participants n=7 Participants	134 Participants n=5 Participants
Age, Customized At least 60 years	155 Participants n=5 Participants	44 Participants n=7 Participants	199 Participants n=5 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	83 Participants n=7 Participants	163 Participants n=5 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	93 Participants n=7 Participants	170 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	126 Participants n=5 Participants	150 Participants n=7 Participants	276 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	27 Participants n=5 Participants	20 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	135 Participants n=5 Participants	156 Participants n=7 Participants	291 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	12 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Canada	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Netherlands	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment United States	59 participants n=5 Participants	86 participants n=7 Participants	145 participants n=5 Participants
Region of Enrollment Poland	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Italy	16 participants n=5 Participants	12 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment United Kingdom	7 participants n=5 Participants	7 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment France	24 participants n=5 Participants	29 participants n=7 Participants	53 participants n=5 Participants
Region of Enrollment Germany	37 participants n=5 Participants	27 participants n=7 Participants	64 participants n=5 Participants
Region of Enrollment Spain	5 participants n=5 Participants	8 participants n=7 Participants	13 participants n=5 Participants
Weight	74.66 kg STANDARD_DEVIATION 14.75 • n=5 Participants	74.76 kg STANDARD_DEVIATION 19.41 • n=7 Participants	74.72 kg STANDARD_DEVIATION 17.33 • n=5 Participants

PRIMARY outcome

Timeframe: Within the first 3 cycles of treatment (84 days)

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

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=112 Participants 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.	Cohort 2; ≥18 Years of Age n=136 Participants 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.
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) Complete remission with incomplete platelet (CRp)	4 participants	2 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) Complete remission with incomplete hematologic CRi	56 participants	55 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) Partial remission (PR)	23 participants	39 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) No response (NR)	20 participants	24 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) Composite complete remission (CRc)	63 participants	62 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) Unknown	6 participants	11 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) Complete remission (CR)	3 participants	5 participants

PRIMARY outcome

Timeframe: Within the first 3 cycles of treatment (84 days)

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

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.

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=44 Participants 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.	Cohort 2; ≥18 Years of Age n=40 Participants 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.
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) Complete remission with incomplete platelet (CRp)	1 participants	1 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) Complete remission with incomplete hematologic CRi	13 participants	10 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) Partial remission (PR)	4 participants	6 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) No response (NR)	17 participants	16 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) Complete remission (CR)	2 participants	1 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) Unknown	7 participants	6 participants
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) Composite complete remission (CRc)	16 participants	12 participants

PRIMARY outcome

Timeframe: within 28 months

Population: Composite complete remission was assessed in the Safety Population.

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.

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=157 Participants 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.	Cohort 2; ≥18 Years of Age n=176 Participants 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.
Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status FLT3-ITD(+)	63 participants	62 participants
Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status FLT3-ITD(-)	16 participants	12 participants

SECONDARY outcome

Timeframe: From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=63 Participants 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.	Cohort 2; ≥18 Years of Age n=62 Participants 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.
Duration of Composite Complete Remission in FLT3-ITD (+) Participants Who Achieved CRc Based on All On-Treatment Data	12.1 weeks Interval 6.3 to 15.7	10.6 weeks Interval 8.1 to 16.1

SECONDARY outcome

Timeframe: From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment

Population: 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).

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=16 Participants 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.	Cohort 2; ≥18 Years of Age n=12 Participants 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.
Duration of Composite Complete Remission in FLT3-ITD (-) Participants Who Achieved CRc Based on All On-Treatment Data	16.4 weeks Interval 8.1 to 30.4	7.0 weeks Interval 4.1 to 8.1

SECONDARY outcome

Timeframe: From the time of any response until disease progression or death, up to approximately 3 years post treatment

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

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).

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=83 Participants 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.	Cohort 2; ≥18 Years of Age n=99 Participants 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.
Duration of Any Response in FLT3-ITD (+) Participants	15.7 weeks Interval 14.1 to 21.3	14.1 weeks Interval 11.1 to 22.3

SECONDARY outcome

Timeframe: From the time of any response until disease progression or death, up to approximately 3 years post treatment

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

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=20 Participants 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.	Cohort 2; ≥18 Years of Age n=18 Participants 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.
Duration of Any Response in FLT3-ITD (-) Participants	22.4 weeks Interval 10.1 to 34.1	8.1 weeks Interval 7.4 to 8.1

SECONDARY outcome

Timeframe: From the time CRc was achieved until disease progression or death, up to approximately 3 years post treatment

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

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).

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=61 Participants 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.	Cohort 2; ≥18 Years of Age n=61 Participants 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.
Median Duration of Leukemia-free Survival in FLT3-ITD (+) Participants	12.1 weeks Interval 6.1 to 14.3	12.9 weeks Interval 9.4 to 19.1

SECONDARY outcome

Timeframe: From the time CRc was achieved until disease progression or death, up to approximately 3 years post treatment

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

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).

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=14 Participants 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.	Cohort 2; ≥18 Years of Age n=11 Participants 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.
Median Duration of Leukemia-free Survival in FLT3-ITD (-) Participants	16.4 weeks Interval 8.1 to 26.1	7.0 weeks Interval 5.0 to 8.1

SECONDARY outcome

Timeframe: Time from first dose to death from any cause, up to 3 years post treatment

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

Kaplan-Meier analysis of overall survival (Safety Population)

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=112 Participants 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.	Cohort 2; ≥18 Years of Age n=136 Participants 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.
Median Duration of Overall Survival in FLT3-ITD (+) Participants	25.4 weeks Interval 21.3 to 29.7	24.0 weeks Interval 21.1 to 27.1

SECONDARY outcome

Timeframe: Time from first dose to death from any cause, up to approximately 3 years post treatment

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

Kaplan-Meier analysis of overall survival (Safety Population)

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=44 Participants 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.	Cohort 2; ≥18 Years of Age n=40 Participants 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.
Median Duration of Overall Survival in FLT3-ITD (-) Participants	19.1 weeks Interval 12.0 to 29.4	25.1 weeks Interval 18.1 to 37.0

SECONDARY outcome

Timeframe: Within first 3 cycles of treatment (84 days)

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

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.

Outcome measures

Outcome measures
Measure	Cohort 1; ≥60 Years of Age n=157 Participants 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.	Cohort 2; ≥18 Years of Age n=176 Participants 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.
Early Treatment-related Death	4 participants	4 participants

Adverse Events

Cohort 1; ≥60 Years of Age

Serious events: 134 serious events

Other events: 151 other events

Deaths: 71 deaths

Cohort 2; ≥18 Years of Age

Serious events: 135 serious events

Other events: 175 other events

Deaths: 60 deaths

Serious adverse events

Other adverse events

Additional Information

Daiichi Sankyo

Contact for Clinical Trial Information

Phone: 1-908-992-6400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Cohort 1; ≥60 Years of Age n=157 participants at risk 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.	Cohort 2; ≥18 Years of Age n=176 participants at risk 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.
Vascular disorders Hematoma	0.64% 1/157 • 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. 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.	1.7% 3/176 • 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. 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.
Vascular disorders Hemorrhage	0.00% 0/157 • 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. 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.	0.57% 1/176 • 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. 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.
Vascular disorders Hypotension	1.9% 3/157 • 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. 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.	0.00% 0/176 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukemia	23.6% 37/157 • 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. 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.	20.5% 36/176 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukemic infiltration brain	0.00% 0/157 • 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. 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.	0.57% 1/176 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphohistiocytosis	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelofibrosis	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/157 • 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. 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.	0.57% 1/176 • 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. 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.
Immune system disorders Graft versus host disease in skin	0.00% 0/157 • 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. 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.	0.57% 1/176 • 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. 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.
General disorders Asthenia	1.3% 2/157 • 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. 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.	0.57% 1/176 • 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. 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.
General disorders Death	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
General disorders Fatigue	0.64% 1/157 • 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. 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.	1.1% 2/176 • 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. 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.
General disorders General physical health deterioration	1.3% 2/157 • 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. 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.	2.3% 4/176 • 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. 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.
General disorders Localized edema	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
General disorders Multi-organ failure	0.00% 0/157 • 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. 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.	1.1% 2/176 • 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. 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.
General disorders Edema peripheral	0.64% 1/157 • 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. 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.	0.57% 1/176 • 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. 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.
General disorders Pain	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
General disorders Pyrexia	6.4% 10/157 • 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. 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.	4.5% 8/176 • 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. 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.
General disorders Secretion discharge	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
General disorders Systemic inflammatory response syndrome	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Psychiatric disorders Anxiety	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Psychiatric disorders Confusional state	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Psychiatric disorders Delirium	0.00% 0/157 • 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. 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.	0.57% 1/176 • 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. 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.
Psychiatric disorders Mental status changes	1.9% 3/157 • 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. 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.	0.57% 1/176 • 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. 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.
Reproductive system and breast disorders Vaginal hemorrhage	0.00% 0/157 • 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. 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.	0.57% 1/176 • 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. 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.
Injury, poisoning and procedural complications Accidental overdose	0.64% 1/157 • 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. 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.	0.57% 1/176 • 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. 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.
Injury, poisoning and procedural complications Accidental poisoning	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Injury, poisoning and procedural complications Endotracheal intubation complication	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Injury, poisoning and procedural complications Head injury	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Injury, poisoning and procedural complications Subdural hematoma	1.9% 3/157 • 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. 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.	0.00% 0/176 • 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. 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.
Injury, poisoning and procedural complications Subdural hemorrhage	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Investigations Alanine aminotransferase increased	0.64% 1/157 • 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. 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.	1.7% 3/176 • 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. 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.
Investigations Aspartate aminotransferase increased	0.00% 0/157 • 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. 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.	0.57% 1/176 • 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. 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.
Investigations Blood bilirubin increased	0.64% 1/157 • 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. 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.	2.3% 4/176 • 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. 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.
Investigations Blood potassium decreased	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Investigations C-reactive protein increased	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.
Investigations Ejection fraction decreased	0.00% 0/157 • 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. 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.	0.57% 1/176 • 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. 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.
Investigations Electrocardiogram QT prolonged	10.8% 17/157 • 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. 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.	9.1% 16/176 • 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. 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.
Investigations Hepatic enzyme increased	0.64% 1/157 • 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. 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.	0.00% 0/176 • 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. 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.

Other adverse events
Measure	Cohort 1; ≥60 Years of Age n=157 participants at risk 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.	Cohort 2; ≥18 Years of Age n=176 participants at risk 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.
Vascular disorders Hematoma	10.8% 17/157 • Number of events 17 • 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. 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.	6.8% 12/176 • Number of events 12 • 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. 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.
Vascular disorders Hypotension	10.8% 17/157 • Number of events 17 • 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. 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.	7.4% 13/176 • Number of events 13 • 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. 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.
General disorders Asthenia	21.0% 33/157 • Number of events 33 • 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. 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.	18.2% 32/176 • Number of events 32 • 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. 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.
General disorders Chest pain	6.4% 10/157 • Number of events 10 • 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. 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.	7.4% 13/176 • Number of events 13 • 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. 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.
General disorders Chills	8.3% 13/157 • Number of events 13 • 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. 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.	8.0% 14/176 • Number of events 14 • 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. 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.
General disorders Fatigue	39.5% 62/157 • Number of events 62 • 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. 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.	27.8% 49/176 • Number of events 49 • 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. 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.
General disorders Mucosal inflammation	5.1% 8/157 • Number of events 8 • 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. 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.	8.5% 15/176 • Number of events 15 • 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. 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.
General disorders Edema peripheral	29.3% 46/157 • Number of events 46 • 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. 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.	25.6% 45/176 • Number of events 45 • 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. 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.
General disorders Pyrexia	29.9% 47/157 • Number of events 47 • 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. 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.	27.8% 49/176 • Number of events 49 • 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. 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.
Psychiatric disorders Confusional state	5.1% 8/157 • Number of events 8 • 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. 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.	1.1% 2/176 • Number of events 2 • 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. 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.
Psychiatric disorders Depression	7.6% 12/157 • Number of events 12 • 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. 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.	5.7% 10/176 • Number of events 10 • 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. 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.
Psychiatric disorders Insomnia	7.0% 11/157 • Number of events 11 • 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. 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.	8.5% 15/176 • Number of events 15 • 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. 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.
Injury, poisoning and procedural complications Contusion	8.9% 14/157 • Number of events 14 • 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. 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.	3.4% 6/176 • Number of events 6 • 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. 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.
Investigations Alanine aminotransferse increased	5.7% 9/157 • Number of events 9 • 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. 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.	8.5% 15/176 • Number of events 15 • 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. 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.
Investigations Aspartate aminotransferase increased	5.1% 8/157 • Number of events 8 • 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. 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.	4.0% 7/176 • Number of events 7 • 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. 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.
Investigations Electrocardiogram QT prolonged	19.7% 31/157 • Number of events 31 • 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. 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.	27.3% 48/176 • Number of events 48 • 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. 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.
Investigations Neutrophil count decreased	5.1% 8/157 • Number of events 8 • 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. 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.	3.4% 6/176 • Number of events 6 • 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. 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.
Investigations Platelet count decreased	10.8% 17/157 • Number of events 17 • 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. 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.	6.8% 12/176 • Number of events 12 • 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. 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.
Investigations Weight decreased	6.4% 10/157 • Number of events 10 • 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. 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.	6.2% 11/176 • Number of events 11 • 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. 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.
Cardiac disorders Tachycardia	6.4% 10/157 • Number of events 10 • 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. 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.	5.7% 10/176 • Number of events 10 • 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. 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.
Blood and lymphatic system disorders Anemia	28.0% 44/157 • Number of events 44 • 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. 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.	27.3% 48/176 • Number of events 48 • 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. 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.
Blood and lymphatic system disorders Febrile neutropenia	7.6% 12/157 • Number of events 12 • 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. 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.	8.0% 14/176 • Number of events 14 • 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. 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.
Blood and lymphatic system disorders Leukopenia	6.4% 10/157 • Number of events 10 • 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. 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.	10.2% 18/176 • Number of events 18 • 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. 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.
Blood and lymphatic system disorders Neutropenia	9.6% 15/157 • Number of events 15 • 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. 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.	11.4% 20/176 • Number of events 20 • 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. 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.
Blood and lymphatic system disorders Pancytopenia	5.7% 9/157 • Number of events 9 • 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. 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.	1.1% 2/176 • Number of events 2 • 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. 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.
Blood and lymphatic system disorders Thrombocytopenia	14.0% 22/157 • Number of events 22 • 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. 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.	14.2% 25/176 • Number of events 25 • 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. 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.
Respiratory, thoracic and mediastinal disorders Cough	16.6% 26/157 • Number of events 26 • 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. 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.	21.0% 37/176 • Number of events 37 • 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. 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.
Respiratory, thoracic and mediastinal disorders Dyspnea	17.8% 28/157 • Number of events 28 • 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. 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.	14.8% 26/176 • Number of events 26 • 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. 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.
Respiratory, thoracic and mediastinal disorders Dyspnea exertional	5.1% 8/157 • Number of events 8 • 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. 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.	1.1% 2/176 • Number of events 2 • 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. 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	18.5% 29/157 • Number of events 29 • 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. 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.	15.3% 27/176 • Number of events 27 • 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. 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.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.1% 8/157 • Number of events 8 • 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. 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.	5.7% 10/176 • Number of events 10 • 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. 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.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.1% 8/157 • Number of events 8 • 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. 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.	6.8% 12/176 • Number of events 12 • 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. 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.
Nervous system disorders Dizziness	17.2% 27/157 • Number of events 27 • 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. 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.	10.2% 18/176 • Number of events 18 • 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. 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.
Nervous system disorders Dysgeusia	28.0% 44/157 • Number of events 44 • 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. 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.	19.3% 34/176 • Number of events 34 • 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. 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.
Nervous system disorders Headache	12.1% 19/157 • Number of events 19 • 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. 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.	13.6% 24/176 • Number of events 24 • 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. 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.
Nervous system disorders Paresthesia	8.3% 13/157 • Number of events 13 • 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. 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.	2.8% 5/176 • Number of events 5 • 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. 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.
Nervous system disorders Tremor	6.4% 10/157 • Number of events 10 • 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. 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.	1.1% 2/176 • Number of events 2 • 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. 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.
Gastrointestinal disorders Abdominal pain	12.1% 19/157 • Number of events 19 • 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. 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.	13.1% 23/176 • Number of events 23 • 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. 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.
Gastrointestinal disorders Abdominal pain upper	15.3% 24/157 • Number of events 24 • 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. 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.	1.7% 3/176 • Number of events 3 • 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. 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.
Gastrointestinal disorders Constipation	22.3% 35/157 • Number of events 35 • 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. 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.	20.5% 36/176 • Number of events 36 • 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. 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.