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

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ClinicalTrials.gov Identifier: NCT02984995
Recruitment Status : Completed
First Posted : December 7, 2016
Results First Posted : February 17, 2020
Last Update Posted : February 17, 2020
Sponsor:
Collaborator:
Daiichi Sankyo, Inc.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia, Myeloid, Acute
Intervention Drug: Quizartinib
Enrollment 37
Recruitment Details A total of 37 participants who met all inclusion and no exclusion criteria were enrolled in the study.
Pre-assignment Details Quizartinib initial dose was 30 mg/day and escalated to 60 mg/day. For subjects receiving strong cytochrome P450 (CYP) 3A4 inhibitors, the initial dose was 20 mg/day. An increase from the initial dose of 30 mg/day to 60 mg/day or 20 mg/day to 30 mg/day was determined on Day 16 of Cycle 1 and Day 1 of Cycle 2 based on dose increase criteria.
Arm/Group Title Initial Dose 30 mg/Day Quizartinib Initial Dose 20 mg/Day Quizartinib
Hide Arm/Group Description Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15. Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15.
Period Title: Overall Study
Started 34 3
Completed 9 0
Not Completed 25 3
Reason Not Completed
Required stem cell transplant             13             2
Progressive disease             11             1
Adverse Event             1             0
Arm/Group Title Initial Dose 30 mg/Day Quizartinib Initial Dose 20 mg/Day Quizartinib Total
Hide Arm/Group Description Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15. Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15. Total of all reporting groups
Overall Number of Baseline Participants 34 3 37
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 3 participants 37 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
15
  44.1%
2
  66.7%
17
  45.9%
>=65 years
19
  55.9%
1
  33.3%
20
  54.1%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 34 participants 3 participants 37 participants
60.2  (14.51) 58.0  (9.92) 60.0  (14.68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 3 participants 37 participants
Female
22
  64.7%
0
   0.0%
22
  59.5%
Male
12
  35.3%
3
 100.0%
15
  40.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 3 participants 37 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
34
 100.0%
3
 100.0%
37
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 34 participants 3 participants 37 participants
34 3 37
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 34 participants 3 participants 37 participants
20.72  (2.53) 22.25  (3.37) 20.84  (2.58)
FLT3-ITD Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 3 participants 37 participants
Positive
29
  85.3%
3
 100.0%
32
  86.5%
Negative
5
  14.7%
0
   0.0%
5
  13.5%
Response to Prior Therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 3 participants 37 participants
Relapse
21
  61.8%
3
 100.0%
24
  64.9%
Refractory
13
  38.2%
0
   0.0%
13
  35.1%
1.Primary Outcome
Title Composite Complete Remission (CRc) Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description The composite complete remission (CRc) rate is defined as the proportion of participants whose best response is complete remission [CR], CR with incomplete platelet recovery [CRp], or CR with incomplete hematological recovery [CRi]) after treatment with quizartinib.
Time Frame Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 up until the end of treatment, except for responses from any subsequent AML therapy including transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with FLT3-ITD positive relapsed or refractory AML who achieved CR, CRp, or CRi, discontinued the study treatment, or completed response assessment at Cycle 4 Day 1.
Arm/Group Title Initial Dose 30 mg/Day Quizartinib Initial Dose 20 mg/Day Quizartinib Total
Hide Arm/Group Description:
Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15.
Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15.
All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Overall Number of Participants Analyzed 23 3 26
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of participants
56.5
(37.5 to 74.2)
33.3
(1.7 to 86.5)
53.8
(36.2 to 70.8)
2.Secondary Outcome
Title Best Response After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description Best response is defined as the best measured response over all response assessments (complete response [CR], CR with incomplete platelet recovery [CRp], CR with incomplete hematological recovery [CRi], partial remission [PR], no response [NR], or Unknown) at all time points after the first dose of the study drug to the end of treatment (does not include response from any subsequent AML therapy including transplantation).
Time Frame Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with FLT3-ITD positive relapsed or refractory AML who achieved CR, CRp, CRi, or PR, discontinued the study treatment, or completed response assessment at Cycle 4 Day 1.
Arm/Group Title Initial Dose 30 mg/Day Quizartinib Initial Dose 20 mg/Day Quizartinib Total
Hide Arm/Group Description:
Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15.
Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15.
All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Overall Number of Participants Analyzed 24 3 27
Measure Type: Count of Participants
Unit of Measure: Participants
Complete response (CR)
0
   0.0%
0
   0.0%
0
   0.0%
Complete response with incomplete platelet (CRp)
1
   4.2%
0
   0.0%
1
   3.7%
Complete response with incomplete hematologic(CRi)
12
  50.0%
1
  33.3%
13
  48.1%
Partial remission (PR)
6
  25.0%
1
  33.3%
7
  25.9%
No response (NR)
5
  20.8%
1
  33.3%
6
  22.2%
3.Secondary Outcome
Title Response Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description [Not Specified]
Time Frame Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with FLT3-ITD positive relapsed or refractory AML who achieved CR, CRp, CRi, or PR, discontinued the study treatment, or completed response assessment at Cycle 4 Day 1.
Arm/Group Title Initial Dose 30 mg/Day Quizartinib Initial Dose 20 mg/Day Quizartinib Total
Hide Arm/Group Description:
Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15.
Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15.
All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Overall Number of Participants Analyzed 24 3 27
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
79.2
(57.8 to 92.9)
66.7
(9.4 to 99.2)
77.8
(57.7 to 91.4)
4.Secondary Outcome
Title Duration of Composite Complete Remission (CRc) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description Duration from the date of first composite complete remission (CRc) (complete remission [CR], CR with incomplete platelet recovery [CRp], or CR with incomplete hematological recovery [CRi]) observed to the date of documented relapse was assessed.
Time Frame Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 up until the end of treatment, except for responses from any subsequent AML therapy including transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with FLT3-ITD positive relapsed or refractory AML who had a documented best response of CRc.
Arm/Group Title Initial Dose 30 mg/Day Quizartinib Initial Dose 20 mg/Day Quizartinib Total
Hide Arm/Group Description:
Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15.
Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15.
All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Overall Number of Participants Analyzed 13 1 14
Median (95% Confidence Interval)
Unit of Measure: weeks
16.1
(4.7 to 24.6)
NA [1] 
(NA to NA)
16.1
(4.7 to 24.6)
[1]
A median value was not reached due to <50% of participants experiencing the event. In a Kaplan-Meier analysis, the curve would never fall below the 50% mark, and would continue to the largest observed censored time value.
5.Secondary Outcome
Title Overall Survival (OS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description OS is defined as the time from registration (enrollment) until death from any cause.
Time Frame Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with FLT3-ITD positive relapsed or refractory AML.
Arm/Group Title Initial Dose 30 mg/Day Quizartinib Initial Dose 20 mg/Day Quizartinib Total
Hide Arm/Group Description:
Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15.
Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15.
All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Overall Number of Participants Analyzed 29 3 32
Median (95% Confidence Interval)
Unit of Measure: weeks
34.1 [1] 
(27.1 to NA)
NA [2] 
(22.6 to NA)
34.1 [1] 
(27.1 to NA)
[1]
Upper limit was expressed as NA since the upper limit was not reached. The upper limit was not estimated because of the small number of events after the median OS time.
[2]
There were not enough events to estimate a standard error for the median survival time"
6.Secondary Outcome
Title Event-free Survival (EFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description Event-free survival is defined as the time from date of registration until documented refractory disease, relapse after response of composite complete remission (CRc = complete remission [CR], CR with incomplete platelet recovery [CRp], or CR with incomplete hematological recovery [CRi]), or death from any cause, whichever occurs first.
Time Frame Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 32 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with FLT3-ITD positive relapsed or refractory AML.
Arm/Group Title Initial Dose 30 mg/Day Quizartinib Initial Dose 20 mg/Day Quizartinib Total
Hide Arm/Group Description:
Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15.
Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15.
All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Overall Number of Participants Analyzed 29 3 32
Median (95% Confidence Interval)
Unit of Measure: weeks
12.7
(0.1 to 24.7)
0.1 [1] 
(0.1 to NA)
12.7
(0.1 to 24.7)
[1]
The missing upper bound is related to right-censored data. The last time point censored and estimate is essentially infinity, therefore it is N/A.
7.Secondary Outcome
Title Leukemia-free Survival (LFS) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description Leukemia-free survival (LFS) is the time from the first documented response of CRc until documented relapse or death from any cause. The analysis for LFS will be conditional on the participant having a documented best response of CRc.
Time Frame Baseline, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1 until the end of treatment, except for responses from any subsequent AML therapy including transplantation up to 28 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with FLT3-ITD positive relapsed or refractory AML and documented best response of CRc.
Arm/Group Title Initial Dose 30 mg/Day Quizartinib Initial Dose 20 mg/Day Quizartinib Total
Hide Arm/Group Description:
Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15.
Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15.
All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Overall Number of Participants Analyzed 29 3 32
Median (95% Confidence Interval)
Unit of Measure: weeks
16.1
(4.7 to 24.6)
NA [1] 
(NA to NA)
16.1
(4.7 to 24.6)
[1]
Lack of a median value is due to less than 50% of the participants experiencing the event. In a Kaplan-Meier analysis, the curve would never fall below the 50% mark, and would continue to the largest observed censored time value.
8.Secondary Outcome
Title Hematopoietic Stem Cell Transplantation Rate After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description Proportion of participants who start hematopoietic stem cell transplantation (HSCT) immediately after the end of treatment with the study drug without receiving other treatment for AML, except for conditioning regiment for HSCT, was assessed.
Time Frame Up to new AML treatment or 1 year post treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with FLT3-ITD positive relapsed or refractory AML who underwent HSCT after treatment.
Arm/Group Title Initial Dose 30 mg/Day Quizartinib Initial Dose 20 mg/Day Quizartinib Total
Hide Arm/Group Description:
Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15.
Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15.
All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
Overall Number of Participants Analyzed 29 3 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
37.9
(20.7 to 57.7)
33.3
(0.8 to 90.6)
37.5
(21.1 to 56.3)
9.Secondary Outcome
Title Change in the Area Under the Plasma Concentration Time Curve (AUC) of Quizartinib and Its Active Metabolite After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description [Not Specified]
Time Frame Cycle 1, Days 1 and 15; Cycle 2, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.
Arm/Group Title Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor) Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor) Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor) Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)
Hide Arm/Group Description:
Patients who received a CYP3A4 strong inhibitor received quizartinib 20 mg/day and escalated to 30 mg/day at Day 15.
Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 30 mg/day.
Patients who received a CYP3A4 strong inhibitor received quizartinib 30 mg/day.
Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 60 mg/day.
Overall Number of Participants Analyzed 3 34 2 21
Mean (Standard Deviation)
Unit of Measure: ng*h/mL
Cycle 1, Day 1; Quizartinib (n=3,34,0,0) Number Analyzed 3 participants 34 participants 0 participants 0 participants
877  (489) 1170  (716)
Cycle 1, Day 1; Active Metabolite (n=3,34,0,0) Number Analyzed 3 participants 34 participants 0 participants 0 participants
75.1  (80.6) 560  (391)
Cycle 1, Day 15; Quizartinib (n=3,32,0,0) Number Analyzed 3 participants 32 participants 0 participants 0 participants
2610  (693) 3970  (2610)
Cycle 1, Day 15; Active Metabolite (n=3,32,0,0) Number Analyzed 3 participants 32 participants 0 participants 0 participants
430  (276) 3120  (1300)
Cycle 2, Day 1; Quizartinib (n=0,0,2,21) Number Analyzed 0 participants 0 participants 2 participants 21 participants
2960  (749) 9240  (6090)
Cycle 2, Day 1; Active Metabolite (n=0,0,2,21) Number Analyzed 0 participants 0 participants 2 participants 21 participants
983  (389) 6530  (2630)
10.Secondary Outcome
Title Change in the Maximum Plasma Concentration (Cmax) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description [Not Specified]
Time Frame Cycle 1, Days 1 and 15; Cycle 2, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.
Arm/Group Title Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor) Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor) Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor) Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)
Hide Arm/Group Description:
Patients who received a CYP3A4 strong inhibitor received quizartinib 20 mg/day and escalated to 30 mg/day at Day 15.
Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 30 mg/day.
Patients who received a CYP3A4 strong inhibitor received quizartinib 30 mg/day.
Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 60 mg/day.
Overall Number of Participants Analyzed 3 34 2 21
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 1, Day 1; Quizartinib (n=3,34,0,0) Number Analyzed 3 participants 34 participants 0 participants 0 participants
48.1  (25.9) 76.9  (46.8)
Cycle 1, Day 1; Active Metabolite (n=3,34,0,0) Number Analyzed 3 participants 34 participants 0 participants 0 participants
3.92  (4.49) 29.1  (20.9)
Cycle 1, Day 15; Quizartinib (n=3,32,0,0) Number Analyzed 3 participants 32 participants 0 participants 0 participants
127  (35.9) 211  (132)
Cycle 1, Day 15; Active Metabolite (n=3,32,0,0) Number Analyzed 3 participants 32 participants 0 participants 0 participants
18.9  (12.1) 146  (60.4)
Cycle 2, Day 1; Quizartinib (n=0,0,2,21) Number Analyzed 0 participants 0 participants 2 participants 21 participants
149  (38.2) 480  (296)
Cycle 2, Day 1; Active Metabolite (n=0,0,2,21) Number Analyzed 0 participants 0 participants 2 participants 21 participants
43.7  (17.7) 298  (118)
11.Secondary Outcome
Title Change in the Trough Plasma Concentration (Ctrough) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description [Not Specified]
Time Frame Cycle 1, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.
Arm/Group Title Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor) Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor) Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor) Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)
Hide Arm/Group Description:
Patients who received a CYP3A4 strong inhibitor received quizartinib 20 mg/day and escalated to 30 mg/day at Day 15.
Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 30 mg/day.
Patients who received a CYP3A4 strong inhibitor received quizartinib 30 mg/day.
Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 60 mg/day.
Overall Number of Participants Analyzed 3 32 0 0
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 1, Day 15; Quizartinib 98.2  (19.7) 128  (92.5)
Cycle 1, Day 15; Active Metabolite 17.8  (11.3) 112  (47.9)
12.Secondary Outcome
Title Change in the Time to Reach Maximum Plasma Concentration (Tmax) of Quizartinib and Its Metabolite (AC886) After Treatment With Quizartinib in Japanese Participants With FLT3-ITD Positive Relapsed or Refractory AML
Hide Description [Not Specified]
Time Frame Cycle 1, Days 1 and 15; Cycle 2, Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) parameters were assessed in the PK Analysis Set.
Arm/Group Title Quizartinib 20 mg/Day (With Use of Strong CYP3A4 Inhibitor) Quizartinib 30 mg/Day (With No Use of Strong CYP3A4 Inhibitor) Quizartinib 30 mg/Day (With Use of Strong CYP3A4 Inhibitor) Quizartinib 60 mg/Day (With No Use of Strong CYP3A4 Inhibitor)
Hide Arm/Group Description:
Patients who received a CYP3A4 strong inhibitor received quizartinib 20 mg/day and escalated to 30 mg/day at Day 15.
Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 30 mg/day.
Patients who received a CYP3A4 strong inhibitor received quizartinib 30 mg/day.
Patients who did not receive a CYP3A4 strong inhibitor received quizartinib 60 mg/day.
Overall Number of Participants Analyzed 3 34 2 21
Median (Full Range)
Unit of Measure: h
Cycle 1, Day 1; Quizartinib (n=3,34,0,0) Number Analyzed 3 participants 34 participants 0 participants 0 participants
4.08
(2.17 to 6.17)
4.03
(1.85 to 24.20)
Cycle 1, Day 1; Active Metabolite (n=2,33,0,0) Number Analyzed 2 participants 33 participants 0 participants 0 participants
24.33
(24.25 to 24.42)
24.32
(3.93 to 24.67)
Cycle 1, Day 15; Quizartinib (n=3,32,0,0) Number Analyzed 3 participants 32 participants 0 participants 0 participants
4.08
(4.08 to 6.25)
3.06
(1.42 to 6.08)
Cycle 1, Day 15; Active Metabolite (n=3,32,0,0) Number Analyzed 3 participants 32 participants 0 participants 0 participants
4.08
(0 to 6.25)
5.82
(0.83 to 24.50)
Cycle 2, Day 1; Quizartinib (n=0,0,2,21) Number Analyzed 0 participants 0 participants 2 participants 21 participants
6.17
(6.08 to 6.24)
3.87
(0 to 6.23)
Cycle 2, Day 1; Active Metabolite (n=0,0,2,21) Number Analyzed 0 participants 0 participants 2 participants 21 participants
14.17
(4.25 to 24.08)
5.65
(0 to 24.02)
Time Frame Adverse events were collected from the signing of the informed consent form through 45 days after last dose of study drug up to approximately 2 years.
Adverse Event Reporting Description Adverse events that emerge (or worsen) from the first dose of study drug to the follow-up visit, 45 days after the last dose of study drug, or start date of new AML post treatment.
 
Arm/Group Title Initial Dose 30 mg/Day Quizartinib Initial 20 mg/Day Quizartinib Total
Hide Arm/Group Description Participants who received an initial dose of 30 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 60 mg/day at Day 15. Participants who received a CYP3A4 strong inhibitor received an initial dose of 20 mg/day of quizartinib and, if no QT prolongation, the dose escalated to 30 mg/day at Day 15. All participants who received either 30 mg/day or 20 mg/day quizartinib as an initial dose.
All-Cause Mortality
Initial Dose 30 mg/Day Quizartinib Initial 20 mg/Day Quizartinib Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/34 (38.24%)   1/3 (33.33%)   14/37 (37.84%) 
Hide Serious Adverse Events
Initial Dose 30 mg/Day Quizartinib Initial 20 mg/Day Quizartinib Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/34 (41.18%)   3/3 (100.00%)   17/37 (45.95%) 
Blood and lymphatic system disorders       
Febrile neutropenia  1  4/34 (11.76%)  2/3 (66.67%)  6/37 (16.22%) 
Anemia  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Disseminated intravascular coagulation  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Neutropenia  1  0/34 (0.00%)  1/3 (33.33%)  1/37 (2.70%) 
Gastrointestinal disorders       
Vomiting  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
General disorders       
Disease progression  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Non-cardiac chest pain  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Edema peripheral  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Infections and infestations       
Bacteremia  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Sepsis  1  1/34 (2.94%)  1/3 (33.33%)  2/37 (5.41%) 
Cellulitis  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Encephalitis  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Pneumonia  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Investigations       
Platelet count decreased  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Respiratory, thoracic and mediastinal disorders       
Hemoptysis  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Organizing pneumonia  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Pleural effusion  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Pneumonitis  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Pneumothorax  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Skin and subcutaneous tissue disorders       
Pyoderma gangrenosum  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Vascular disorders       
Hematoma  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
Shock hemorrhagic  1  1/34 (2.94%)  0/3 (0.00%)  1/37 (2.70%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Initial Dose 30 mg/Day Quizartinib Initial 20 mg/Day Quizartinib Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   34/34 (100.00%)   3/3 (100.00%)   37/37 (100.00%) 
Blood and lymphatic system disorders       
Febrile neutropenia  1  10/34 (29.41%)  0/3 (0.00%)  10/37 (27.03%) 
Anemia  1  8/34 (23.53%)  1/3 (33.33%)  9/37 (24.32%) 
Thrombocytopenia  1  3/34 (8.82%)  1/3 (33.33%)  4/37 (10.81%) 
Neutropenia  1  1/34 (2.94%)  1/3 (33.33%)  2/37 (5.41%) 
Gastrointestinal disorders       
Nausea  1  9/34 (26.47%)  2/3 (66.67%)  11/37 (29.73%) 
Vomiting  1  6/34 (17.65%)  0/3 (0.00%)  6/37 (16.22%) 
Diarrhea  1  4/34 (11.76%)  0/3 (0.00%)  4/37 (10.81%) 
Constipation  1  2/34 (5.88%)  1/3 (33.33%)  3/37 (8.11%) 
Stomatitis  1  3/34 (8.82%)  0/3 (0.00%)  3/37 (8.11%) 
Proctalgia  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
General disorders       
Pyrexia  1  4/34 (11.76%)  1/3 (33.33%)  5/37 (13.51%) 
Edema  1  2/34 (5.88%)  1/3 (33.33%)  3/37 (8.11%) 
Malaise  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Edema peripheral  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Hepatobiliary disorders       
Liver disorder  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Infections and infestations       
Acarodermatitis  1  3/34 (8.82%)  0/3 (0.00%)  3/37 (8.11%) 
Pneumonia  1  3/34 (8.82%)  0/3 (0.00%)  3/37 (8.11%) 
Bacteremia  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Cellulitis  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Device-related infections  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Injury, poisoning and procedural complications       
Fall  1  2/34 (5.88%)  1/3 (33.33%)  3/37 (8.11%) 
Transfusion reaction  1  0/34 (0.00%)  2/3 (66.67%)  2/37 (5.41%) 
Investigations       
Electrocardiogram QT prolonged  1  12/34 (35.29%)  1/3 (33.33%)  13/37 (35.14%) 
Platelet count decreased  1  13/34 (38.24%)  0/3 (0.00%)  13/37 (35.14%) 
Neutrophil count decreased  1  8/34 (23.53%)  0/3 (0.00%)  8/37 (21.62%) 
White blood cell count decreased  1  8/34 (23.53%)  0/3 (0.00%)  8/37 (21.62%) 
Alanine aminotransferase increased  1  4/34 (11.76%)  0/3 (0.00%)  4/37 (10.81%) 
Gamma-glutamyltransferase increased  1  3/34 (8.82%)  0/3 (0.00%)  3/37 (8.11%) 
Liver function test increased  1  3/34 (8.82%)  0/3 (0.00%)  3/37 (8.11%) 
Aspartate aminotransferase increased  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Blood uric acid increased  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Metabolism and nutrition disorders       
Decreased appetite  1  4/34 (11.76%)  1/3 (33.33%)  5/37 (13.51%) 
Hypokalemia  1  4/34 (11.76%)  0/3 (0.00%)  4/37 (10.81%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  3/34 (8.82%)  1/3 (33.33%)  4/37 (10.81%) 
Neck pain  1  3/34 (8.82%)  0/3 (0.00%)  3/37 (8.11%) 
Nervous system disorders       
Headache  1  4/34 (11.76%)  0/3 (0.00%)  4/37 (10.81%) 
Dysgeusia  1  3/34 (8.82%)  0/3 (0.00%)  3/37 (8.11%) 
Peripheral sensory neuropathy  1  3/34 (8.82%)  0/3 (0.00%)  3/37 (8.11%) 
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Skin and subcutaneous tissue disorders       
Rash  1  3/34 (8.82%)  1/3 (33.33%)  4/37 (10.81%) 
Urticaria  1  3/34 (8.82%)  0/3 (0.00%)  3/37 (8.11%) 
Pruritus  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Rash maculo-papular  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
Vascular disorders       
Hypotension  1  1/34 (2.94%)  1/3 (33.33%)  2/37 (5.41%) 
Phlebitis  1  2/34 (5.88%)  0/3 (0.00%)  2/37 (5.41%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Contact for Clinical Trial Information
Organization: Daiichi Sankyo Co., Ltd.
Phone: 908-992-6400
EMail: CTRinfo@dsi.com
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc. ( Daiichi Sankyo Co., Ltd. )
ClinicalTrials.gov Identifier: NCT02984995    
Other Study ID Numbers: AC220-A-J201
JAPIC CTI-163441 ( Other Identifier: JAPIC CTI )
First Submitted: December 5, 2016
First Posted: December 7, 2016
Results First Submitted: September 25, 2019
Results First Posted: February 17, 2020
Last Update Posted: February 17, 2020