Trial Outcomes & Findings for (QuANTUM-R): An Open-label Study of Quizartinib Monotherapy vs. Salvage Chemotherapy in Acute Myeloid Leukemia (AML) Subjects Who Are FLT3-ITD Positive (NCT NCT02039726)

NCT ID: NCT02039726

Last Updated: 2021-02-24

Results Overview

Overall Survival is defined as the time (in weeks) from the date of randomization to the date of death due to any cause. Median and quartiles are calculated using the Kaplan-Meier method.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

367 participants

Primary outcome timeframe

At approximately 3 years 9 months

Results posted on

2021-02-24

Participant Flow

A total of 367 participants who met the inclusion and none of the exclusion criteria were randomized (intent-to-treat population); 335 received study drug (safety analysis set).

Prior to randomization, the investigator was required to pre-select 1 of the 3 salvage chemotherapy regimens for each participant. Randomization was stratified by response to prior therapy (relapsed in ≤6 months \[with or without HSCT\] or refractory) and pre-selected salvage chemotherapy (high or low intensity chemotherapy) for all participants.

Participant milestones

Participant milestones
Measure	Quizartinib Participants who were randomized to receive 20 or 30 mg Quizartinib tablets administered orally once daily.	Salvage Chemotherapy Participants who were randomized to receive salvage chemotherapy, such as low dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA), were administered during 28-day cycles.
Overall Study STARTED	245	122
Overall Study Ongoing (as of Data Cutoff)	45	16
Overall Study Did Not Receive Treatment	4	28
Overall Study COMPLETED	200	106
Overall Study NOT COMPLETED	45	16

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

(QuANTUM-R): An Open-label Study of Quizartinib Monotherapy vs. Salvage Chemotherapy in Acute Myeloid Leukemia (AML) Subjects Who Are FLT3-ITD Positive

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Quizartinib n=245 Participants Participants who were randomized to receive 20 or 30 mg Quizartinib tablets administered orally once daily.	Salvage Chemotherapy n=122 Participants Participants who were randomized to receive salvage chemotherapy, such as low dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA), were administered during 28-day cycles.	Total n=367 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	180 Participants n=93 Participants	89 Participants n=4 Participants	269 Participants n=27 Participants
Age, Categorical >=65 years	65 Participants n=93 Participants	33 Participants n=4 Participants	98 Participants n=27 Participants
Age, Continuous	55.0 years n=93 Participants	57.5 years n=4 Participants	56.0 years n=27 Participants
Sex: Female, Male Female	132 Participants n=93 Participants	58 Participants n=4 Participants	190 Participants n=27 Participants
Sex: Female, Male Male	113 Participants n=93 Participants	64 Participants n=4 Participants	177 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Asian	24 Participants n=93 Participants	16 Participants n=4 Participants	40 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	9 Participants n=93 Participants	3 Participants n=4 Participants	12 Participants n=27 Participants
Race (NIH/OMB) White	184 Participants n=93 Participants	93 Participants n=4 Participants	277 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	27 Participants n=93 Participants	10 Participants n=4 Participants	37 Participants n=27 Participants
Region of Enrollment Singapore	0 participants n=93 Participants	2 participants n=4 Participants	2 participants n=27 Participants
Region of Enrollment Hong Kong	5 participants n=93 Participants	3 participants n=4 Participants	8 participants n=27 Participants
Region of Enrollment Hungary	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Region of Enrollment United States	82 participants n=93 Participants	36 participants n=4 Participants	118 participants n=27 Participants
Region of Enrollment Czechia	2 participants n=93 Participants	0 participants n=4 Participants	2 participants n=27 Participants
Region of Enrollment United Kingdom	21 participants n=93 Participants	14 participants n=4 Participants	35 participants n=27 Participants
Region of Enrollment Spain	15 participants n=93 Participants	6 participants n=4 Participants	21 participants n=27 Participants
Region of Enrollment Canada	18 participants n=93 Participants	5 participants n=4 Participants	23 participants n=27 Participants
Region of Enrollment Netherlands	2 participants n=93 Participants	1 participants n=4 Participants	3 participants n=27 Participants
Region of Enrollment South Korea	11 participants n=93 Participants	7 participants n=4 Participants	18 participants n=27 Participants
Region of Enrollment Belgium	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Region of Enrollment Taiwan	2 participants n=93 Participants	1 participants n=4 Participants	3 participants n=27 Participants
Region of Enrollment Poland	2 participants n=93 Participants	0 participants n=4 Participants	2 participants n=27 Participants
Region of Enrollment Italy	34 participants n=93 Participants	19 participants n=4 Participants	53 participants n=27 Participants
Region of Enrollment Australia	3 participants n=93 Participants	3 participants n=4 Participants	6 participants n=27 Participants
Region of Enrollment France	20 participants n=93 Participants	7 participants n=4 Participants	27 participants n=27 Participants
Region of Enrollment Serbia	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Region of Enrollment Germany	25 participants n=93 Participants	18 participants n=4 Participants	43 participants n=27 Participants

PRIMARY outcome

Timeframe: At approximately 3 years 9 months

Overall Survival is defined as the time (in weeks) from the date of randomization to the date of death due to any cause. Median and quartiles are calculated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Quizartinib n=245 Participants Participants who were randomized to receive 20 or 30 mg quizartinib tablets administered orally once daily.	Salvage Chemotherapy n=122 Participants Participants who were randomized to receive salvage chemotherapy, such as low dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA), were administered during 28-day cycles.
Overall Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy	27.0 weeks Interval 15.4 to 62.6	20.4 weeks Interval 8.3 to 39.6

SECONDARY outcome

Timeframe: At approximately 3 years 9 months

Population: Event-free survival was assessed in the intent-to-treat (ITT) analysis set.

Event-free survival is defined as the time (in weeks) from randomization until documented refractory disease, relapse after complete composite remission (CRc), or death from any cause, whichever is observed first.

Outcome measures

Outcome measures
Measure	Quizartinib n=245 Participants Participants who were randomized to receive 20 or 30 mg quizartinib tablets administered orally once daily.	Salvage Chemotherapy n=122 Participants Participants who were randomized to receive salvage chemotherapy, such as low dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA), were administered during 28-day cycles.
Event-free Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy	6.0 weeks Interval 0.1 to 19.7	3.7 weeks Interval 0.1 to 17.0

Adverse Events

Quizartinib

Serious events: 168 serious events

Other events: 238 other events

Deaths: 80 deaths

Salvage Chemotherapy

Serious events: 37 serious events

Other events: 91 other events

Deaths: 16 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

Other adverse events
Measure	Quizartinib n=241 participants at risk Participants who were randomized to receive 20 or 30 mg quizartinib tablets administered orally once daily.	Salvage Chemotherapy n=94 participants at risk Participants who were randomized to receive salvage chemotherapy, such as low dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA), were administered during 28-day cycles.
Vascular disorders Hypertension	3.7% 9/241 • Number of events 9 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	8.5% 8/94 • Number of events 8 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Vascular disorders Hypotension	13.3% 32/241 • Number of events 39 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	10.6% 10/94 • Number of events 10 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Immune system disorders Graft versus host disease	5.8% 14/241 • Number of events 14 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	0.00% 0/94 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Immune system disorders Graft versus host disease in skin	6.6% 16/241 • Number of events 18 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	0.00% 0/94 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
General disorders Asthenia	14.1% 34/241 • Number of events 38 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	10.6% 10/94 • Number of events 11 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
General disorders Chills	6.2% 15/241 • Number of events 15 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	7.4% 7/94 • Number of events 8 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
General disorders Fatigue	27.8% 67/241 • Number of events 81 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	19.1% 18/94 • Number of events 22 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
General disorders Edema peripheral	21.2% 51/241 • Number of events 58 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	23.4% 22/94 • Number of events 26 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
General disorders Pain	7.9% 19/241 • Number of events 21 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	8.5% 8/94 • Number of events 8 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
General disorders Pyrexia	36.5% 88/241 • Number of events 130 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	44.7% 42/94 • Number of events 69 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Psychiatric disorders Anxiety	7.9% 19/241 • Number of events 21 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	4.3% 4/94 • Number of events 4 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Psychiatric disorders Confusional state	2.9% 7/241 • Number of events 7 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	5.3% 5/94 • Number of events 5 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Psychiatric disorders Insomnia	9.1% 22/241 • Number of events 24 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	13.8% 13/94 • Number of events 13 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Injury, poisoning and procedural complications Contusion	6.2% 15/241 • Number of events 17 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	2.1% 2/94 • Number of events 2 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Investigations Alanine aminotransferase increased	13.3% 32/241 • Number of events 46 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	4.3% 4/94 • Number of events 5 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Investigations Aspartate aminotransferase increased	10.8% 26/241 • Number of events 41 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	1.1% 1/94 • Number of events 1 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Investigations Blood alkaline phosphatase increased	7.5% 18/241 • Number of events 24 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	4.3% 4/94 • Number of events 5 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Investigations Blood bilirubin increased	10.0% 24/241 • Number of events 30 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	3.2% 3/94 • Number of events 6 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Investigations Blood creatinine increased	6.6% 16/241 • Number of events 22 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	2.1% 2/94 • Number of events 2 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Investigations Electrocardiogram QT prolonged	26.1% 63/241 • Number of events 90 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	2.1% 2/94 • Number of events 2 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Investigations Neutrophil count decreased	12.9% 31/241 • Number of events 46 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	14.9% 14/94 • Number of events 21 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Investigations Platelet count decreased	13.7% 33/241 • Number of events 39 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	12.8% 12/94 • Number of events 20 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Investigations Weight decreased	11.2% 27/241 • Number of events 31 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	5.3% 5/94 • Number of events 5 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Investigations White blood cell count decreased	14.5% 35/241 • Number of events 45 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	14.9% 14/94 • Number of events 17 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Cardiac disorders Sinus tachycardia	3.3% 8/241 • Number of events 8 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	5.3% 5/94 • Number of events 5 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Respiratory, thoracic and mediastinal disorders Cough	23.2% 56/241 • Number of events 64 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	13.8% 13/94 • Number of events 14 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Respiratory, thoracic and mediastinal disorders Dyspnea	19.9% 48/241 • Number of events 61 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	8.5% 8/94 • Number of events 11 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Respiratory, thoracic and mediastinal disorders Epistaxis	11.6% 28/241 • Number of events 34 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	8.5% 8/94 • Number of events 9 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.7% 9/241 • Number of events 9 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	5.3% 5/94 • Number of events 5 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.4% 25/241 • Number of events 26 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	6.4% 6/94 • Number of events 7 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.8% 14/241 • Number of events 14 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	2.1% 2/94 • Number of events 2 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Blood and lymphatic system disorders Anemia	35.7% 86/241 • Number of events 131 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	30.9% 29/94 • Number of events 35 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Blood and lymphatic system disorders Febrile neutropenia	17.0% 41/241 • Number of events 47 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	20.2% 19/94 • Number of events 28 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Blood and lymphatic system disorders Leukocytosis	5.8% 14/241 • Number of events 14 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	3.2% 3/94 • Number of events 3 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Blood and lymphatic system disorders Leukopenia	5.4% 13/241 • Number of events 17 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	2.1% 2/94 • Number of events 2 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Blood and lymphatic system disorders Neutropenia	19.9% 48/241 • Number of events 77 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	11.7% 11/94 • Number of events 11 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Blood and lymphatic system disorders Thrombocytopenia	25.7% 62/241 • Number of events 84 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	21.3% 20/94 • Number of events 21 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Nervous system disorders Dizziness	14.9% 36/241 • Number of events 41 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	10.6% 10/94 • Number of events 10 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Nervous system disorders Dysgeusia	9.1% 22/241 • Number of events 22 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	1.1% 1/94 • Number of events 1 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.
Nervous system disorders Headache	21.2% 51/241 • Number of events 64 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.	17.0% 16/94 • Number of events 19 • Treatment-emergent adverse events (TEAEs) were collected from the first dose of study drug to 30 days after the last dose (or longer if assessed as treatment related). All safety events are reported for participants in the Safety Analysis Set who received at least 1 dose of study drug or salvage chemotherapy. Differences in treatment regimens make the Treatment-emergent adverse events (TEAE) collection period span multiple 28-day cycles in the Quizartinib arm and only 1-2 weeks in the salvage chemotherapy arm.