Open Label Study to Evaluate Safety and Efficacy of 2 Doses of Quizartinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01565668
• Collaborator: Ambit Biosciences Corporation (Industry)
• Enrollment: 76
• Locations: 24
• Arms: 2
• Duration (Months): 35
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will evaluate two doses of Quizartinib in patients with relapsed or refractory acute myeloid leukemia who are also FMS-like tyrosine kinase - internal tandem duplication ( FLT3-ITD) positive. Patient will be randomly assigned in a 1:1 ratio to one of two treatment arms. Both treatment arms will receive Quizartinib but at different doses. The study treatment is taken orally in 28 day cycles until either disease progression occurs or an unacceptable toxicity occurs. In addition to the study assessments to evaluate the disease, blood will be drawn to measure drug levels and biomarkers. Patients will be followed for survival at three month intervals after the end of treatment.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute	Drug: AC220	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Open-Label Study of the Safety and Efficacy of Two Doses of Quizartinib (AC220; ASP2689) in Subjects With FLT3-ITD Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AC220 Dose Level 1	Drug: AC220; oral; Other Names: Quizartinib ASP2689
Experimental: AC220 Dose Level 2	Drug: AC220; oral; Other Names: Quizartinib ASP2689

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Achieved Composite Complete Response (CRc) (Intent-to-Treat Population) [At end of Cycle 2 (after two complete 28-day cycles post treatment)]

   CRc is defined as Complete remission (CR) + Complete remission with incomplete platelet recovery (CRp) + Complete remission with incomplete hematological recovery (CRi). Participants with CR must have normal hematopoietic cells and achieved a morphologic leukemia-free state (<5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have had an absolute neutrophil count (ANC) ≥1 × 10^9/L and platelet count ≥100 × 10^9/L and were red blood cell (RBC) and platelet transfusion independent. Blasts in the peripheral blood was to be ≤1% (if blood sample was available). Participants with CRp must have achieved CR except for incomplete platelet recovery (< 100 ×10^9/L). Participants with CRi must have fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia <1 × 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required.

Secondary Outcome Measures

1. Number of Participants Who Achieved Complete Remission (CR) (Intent-to-Treat Population) [At end of treatment visit (approximately 3 years post treatment)]

   Participant must have bone marrow regenerating normal hematopoietic cells and achieve a morphologic leukemia-free state (< 5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have an absolute neutrophil count (ANC) ≥ 1x10^9/L and platelet count ≥ 100 x 10^9/L and they will be red blood cell (RBC) and platelet transfusion independent (defined as 4 weeks without RBC transfusions and 1 week without platelet transfusion).

2. Overall Survival (OS) After Approximately 3 Years (Intent-to-Treat Population) [Evaluated at end of study, up to 6 months (approximately 3 years post treatment)]

   OS was defined as the time from the date of randomization until the date of death from any cause.

3. Event Free Survival (EFS) After Approximately 3 Years (Intent-to-Treat Population) [Evaluated at end of study, up to 6 months (approximately 3 years post treatment)]

   EFS was defined as the time from the date of randomization until the date of documented relapse or death.

4. Leukemia Free Survival (LFS) After Approximately 3 Years (Intent-to-Treat Population) [Evaluated at end of study, up to 6 months (approximately 3 years post treatment)]

   LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc.

5. Duration of Remission After Approximately 3 Years (Intent-to-Treat Population) [Evaluated at end of study, up to 6 months (approximately 3 years post treatment)]

   Duration of remission was defined as the time from first documented remission until documented relapse. CRc was defined as composite complete remission and CRi was defined as complete remission with incomplete hematological recovery.

6. Time to Composite Complete Remission (CRc) in Participants Who Achieved CRc After Approximately 3 Years (Intent-to-Treat Population) [Evaluated at end of study, up to 6 months (approximately 3 years post treatment)]

   Time to CRc was defined as the time from the date of randomization until the first disease assessment of CRc. Time to CRc was only evaluated in participants who achieved CRc.

7. Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population) [Evaluated at end of study, up to 6 months (approximately 3 years post treatment)]

   Transplantation rate was defined as the percentage of participants who underwent HSCT directly after treatment with quizartinib (no other intervening acute myeloid leukemia therapies other than conditioning regimens for the HSCT).

8. Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) [Evaluated at end of study, up to 6 months (approximately 3 years post treatment)]

   QT interval corrected for heart rate using Fridericia's formula (QTcF) grading was to be done according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and the definition of Grade 2 or higher prolongation is QTcF more than 480 msec.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject has morphologically documented primary acute myeloid leukemia (AML) or AML secondary to myelodysplastic syndrome (MDS) as defined by the World Health Organization (WHO) criteria, as determined by pathology review at the treating institution and has relapsed or is refractory after 1 second line (salvage) regimen or after hematopoietic stem cell transplantation (HSCT)

• Subject is positive for FLT3-ITD activating mutation in bone marrow or peripheral blood (>10% allelic ratio)

• Eastern Cooperative Oncology Group performance status of 0 to 2

• In the absence of rapidly progressing disease clearly documented by the investigator, the interval from prior treatment to time of AC220 administration will be at least 2 weeks (14 days) for prior cytotoxic agents or at least 5 half-lives for prior noncytotoxic agents, including immunosuppressive therapy post HSCT

• Persistent chronic clinically significant nonhematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade ≤ 1

• Patients - both males and females - with reproductive potential are eligible

Exclusion Criteria:

• Subject received previous treatment with AC220

• Subject has a diagnosis of acute promyelocytic leukemia

• Subject has a diagnosis of chronic myelogenous leukemia (CML) in blast crisis

• Subject has AML or antecedent MDS secondary to prior chemotherapy

• Subject has had HSCT and has either of the following:

• Donor lymphocyte infusion (DLI) is not permitted during the study or < 30 days prior to study entry

• Subject has clinically active central nervous system (CNS) leukemia. A subject is considered eligible if CNS leukemia is controlled and subject is receiving intrathecal (IT) therapy at study entry. Subjects should continue to receive IT therapy (or cranial radiation) as clinically indicated

• Subject has received concurrent chemotherapy, immunotherapy, or radiotherapy within 14 days prior to the first dose of AC220, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug

• Subject requires treatment with concomitant drugs that prolong QT/QTc interval or with strong inhibitors or inducers of cytochrome P450- isozyme3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care post-transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject

• Subject requires treatment with anticoagulant therapy

• Subject has a known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen

• Subject had major surgery within 4 weeks prior to first dose of AC220

• Subject has uncontrolled or significant cardiovascular disease, including

• Subject has a pre-existing disorder predisposing the subject to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML)

• Subject has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection

• Subject has any of the following laboratory values:

• Subject is a female with a positive pregnancy test, pregnant, or breastfeeding

• Subject has any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA School of Medicine	Los Angeles	California	United States	90095
2	Northwestern University	Chicago	Illinois	United States	60611
3	University of Chicago	Chicago	Illinois	United States	60637
4	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
5	John Hopkins University	Baltimore	Maryland	United States	21231
6	Tufts University School of Medicine-Tufts Medical Center	Boston	Massachusetts	United States	02111
7	University of Minnesota	Minneapolis	Minnesota	United States	55455
8	Mayo Clinic	Rochester	Minnesota	United States	55905
9	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
10	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
11	Weill Cornell Medical College	New York	New York	United States	10065
12	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
13	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
14	Medical University of South Carolina, Hollings Cancer Center	Charleston	South Carolina	United States	29403
15	Vanderbilt University, Vanderbilt Ingram Cancer Center	Nashville	Tennessee	United States	37232
16	UT Southwestern Medical Center, Simmons Cancer Center	Dallas	Texas	United States	75390
17	MD Anderson	Houston	Texas	United States	77030
18	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
19	CHU d'Angers	Angers		France	49033
20	CHU de Grenoble	Grenoble		France	38043
21	Hôpital Saint Antoine	Paris		France	75571
22	Hôpital Haut Lévêque	Pessac		France	33600
23	Universitaria Policlinico S. Orsola Malpighi, Institute of Hemtology "L. & A. Seragnoli"	Bologna		Italy	40138
24	Nottingham University Hospitals	Nottingham	England	United Kingdom

Sponsors and Collaborators

• Daiichi Sankyo, Inc.
• Ambit Biosciences Corporation

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT01565668
• Other Study ID Numbers: 2689-CL-2004; 2011-005408-13
• First Posted: Mar 29, 2012
• Last Update Posted: Dec 27, 2019
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Daiichi Sankyo, Inc.: FLT3-ITD positive Acute Myeloid Leukemia (AML); AC220; Relapse; Refractory
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute

Study Results

Participant Flow

Recruitment Details	A total of 76 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study (intent-to-treat population). Participants were enrolled at 22 clinic sites in North America and Europe (14 sites in the United States, 6 in France, 1 in Italy, and 1 in the United Kingdom).
Pre-assignment Detail	Participants were randomized (1:1) to receive 30 or 60 mg/day quizartinib. These doses were selected based on evidence of efficacy and safety observed in studies AC220-001 and AC220-002, and preclinical data.Two participants who were randomized to quizartinib (60 mg/day) did not receive study drug and are not included in the safety data.

Arm/Group Title	Quizartinib 30 mg	Quizartinib 60 mg
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.	Participants randomized to receive 60 mg quizartinib once daily.
Period Title: Overall Study
STARTED	38	38
Completed Treatment Per Protocol	0	0
Started 30-day Follow-up	37	37
Completed 30-day Follow-up	11	5
Started Long-term Follow-up	36	33
Completed Long-term Follow-up	0	0
COMPLETED	0	0
NOT COMPLETED	38	38

Baseline Characteristics

Arm/Group Title	Quizartinib 30 mg	Quizartinib 60 mg	Total
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.	Participants were randomized to receive 60 mg quizartinib once daily.	Total of all reporting groups
Overall Participants	38	38	76
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56.5	53.0	54.5
Sex: Female, Male (Count of Participants)
Female	16 42.1%	16 42.1%	32 42.1%
Male	22 57.9%	22 57.9%	44 57.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.6%	2 5.3%	3 3.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 2.6%	2 5.3%	3 3.9%
White	29 76.3%	30 78.9%	59 77.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	7 18.4%	4 10.5%	11 14.5%
Region of Enrollment (participants) [Number]
United States	29 76.3%	29 76.3%	58 76.3%
Italy	0 0%	3 7.9%	3 3.9%
United Kingdom	2 5.3%	1 2.6%	3 3.9%
France	7 18.4%	5 13.2%	12 15.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Achieved Composite Complete Response (CRc) (Intent-to-Treat Population)
Description	CRc is defined as Complete remission (CR) + Complete remission with incomplete platelet recovery (CRp) + Complete remission with incomplete hematological recovery (CRi). Participants with CR must have normal hematopoietic cells and achieved a morphologic leukemia-free state (<5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have had an absolute neutrophil count (ANC) ≥1 × 10^9/L and platelet count ≥100 × 10^9/L and were red blood cell (RBC) and platelet transfusion independent. Blasts in the peripheral blood was to be ≤1% (if blood sample was available). Participants with CRp must have achieved CR except for incomplete platelet recovery (< 100 ×10^9/L). Participants with CRi must have fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia <1 × 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required.
Time Frame	At end of Cycle 2 (after two complete 28-day cycles post treatment)

Outcome Measure Data

Analysis Population Description

Composite complete remission was assessed in the intent-to-treat (ITT) analysis set.

Arm/Group Title	Quizartinib 30 mg	Quizartinib 60 mg
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.	Participants randomized to receive 60 mg quizartinib once daily.
Measure Participants	38	38
Count of Participants [Participants]	18 47.4%	18 47.4%

2. Secondary Outcome

Title	Number of Participants Who Achieved Complete Remission (CR) (Intent-to-Treat Population)
Description	Participant must have bone marrow regenerating normal hematopoietic cells and achieve a morphologic leukemia-free state (< 5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have an absolute neutrophil count (ANC) ≥ 1x10^9/L and platelet count ≥ 100 x 10^9/L and they will be red blood cell (RBC) and platelet transfusion independent (defined as 4 weeks without RBC transfusions and 1 week without platelet transfusion).
Time Frame	At end of treatment visit (approximately 3 years post treatment)

Outcome Measure Data

Analysis Population Description

Complete remission was assessed in the intent-to-treat (ITT) analysis set.

Arm/Group Title	Quizartinib 30 mg	Quizartinib 60 mg
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.	Participants randomized to receive 60 mg quizartinib once daily.
Measure Participants	38	38
Count of Participants [Participants]	2 5.3%	1 2.6%

3. Secondary Outcome

Title	Overall Survival (OS) After Approximately 3 Years (Intent-to-Treat Population)
Description	OS was defined as the time from the date of randomization until the date of death from any cause.
Time Frame	Evaluated at end of study, up to 6 months (approximately 3 years post treatment)

Outcome Measure Data

Analysis Population Description

OS was assessed in the intent-to-treat (ITT) analysis set.

Arm/Group Title	Quizartinib 30 mg	Quizartinib 60 mg
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.	Participants randomized to receive 60 mg quizartinib once daily.
Measure Participants	38	38
Median (95% Confidence Interval) [weeks]	20.9	27.3

4. Secondary Outcome

Title	Event Free Survival (EFS) After Approximately 3 Years (Intent-to-Treat Population)
Description	EFS was defined as the time from the date of randomization until the date of documented relapse or death.
Time Frame	Evaluated at end of study, up to 6 months (approximately 3 years post treatment)

Outcome Measure Data

Analysis Population Description

EFS was assessed in the intent-to-treat (ITT) analysis set.

Arm/Group Title	Quizartinib 30 mg	Quizartinib 60 mg
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.	Participants randomized to receive 60 mg quizartinib once daily.
Measure Participants	38	38
Median (95% Confidence Interval) [weeks]	12.0	13.7

5. Secondary Outcome

Title	Leukemia Free Survival (LFS) After Approximately 3 Years (Intent-to-Treat Population)
Description	LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc.
Time Frame	Evaluated at end of study, up to 6 months (approximately 3 years post treatment)

Outcome Measure Data

Analysis Population Description

LFS was assessed in the intent-to-treat (ITT) analysis set.

Arm/Group Title	Quizartinib 30 mg	Quizartinib 60 mg
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.	Participants randomized to receive 60 mg quizartinib once daily.
Measure Participants	18	18
Median (95% Confidence Interval) [weeks]	4.1	9.1

6. Secondary Outcome

Title	Duration of Remission After Approximately 3 Years (Intent-to-Treat Population)
Description	Duration of remission was defined as the time from first documented remission until documented relapse. CRc was defined as composite complete remission and CRi was defined as complete remission with incomplete hematological recovery.
Time Frame	Evaluated at end of study, up to 6 months (approximately 3 years post treatment)

Outcome Measure Data

Analysis Population Description

Duration of remission was assessed in the intent-to-treat (ITT) analysis set.

Arm/Group Title	Quizartinib 30 mg	Quizartinib 60 mg
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.	Participants randomized to receive 60 mg quizartinib once daily.
Measure Participants	38	38
CRc	4.2	9.1
CRi	4.1	20.0

7. Secondary Outcome

Title	Time to Composite Complete Remission (CRc) in Participants Who Achieved CRc After Approximately 3 Years (Intent-to-Treat Population)
Description	Time to CRc was defined as the time from the date of randomization until the first disease assessment of CRc. Time to CRc was only evaluated in participants who achieved CRc.
Time Frame	Evaluated at end of study, up to 6 months (approximately 3 years post treatment)

Outcome Measure Data

Analysis Population Description

Time to CRc was assessed in the intent-to-treat (ITT) analysis set.

Arm/Group Title	Quizartinib 30 mg	Quizartinib 60 mg
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.	Participants randomized to receive 60 mg quizartinib once daily.
Measure Participants	18	18
Median (95% Confidence Interval) [weeks]	4.4	4.6

8. Secondary Outcome

Title	Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population)
Description	Transplantation rate was defined as the percentage of participants who underwent HSCT directly after treatment with quizartinib (no other intervening acute myeloid leukemia therapies other than conditioning regimens for the HSCT).
Time Frame	Evaluated at end of study, up to 6 months (approximately 3 years post treatment)

Outcome Measure Data

Analysis Population Description

Transplantation rate was assessed in the intent-to-treat (ITT) analysis set.

Arm/Group Title	Quizartinib 30 mg	Quizartinib 60 mg
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.	Participants randomized to receive 60 mg quizartinib once daily.
Measure Participants	38	38
Yes	31.6 83.2%	42.1 110.8%
No	68.4 180%	55.3 145.5%
Unknown	0 0%	2.6 6.8%

9. Secondary Outcome

Title	Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set)
Description	QT interval corrected for heart rate using Fridericia's formula (QTcF) grading was to be done according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and the definition of Grade 2 or higher prolongation is QTcF more than 480 msec.
Time Frame	Evaluated at end of study, up to 6 months (approximately 3 years post treatment)

Outcome Measure Data

Analysis Population Description

QTcF prolongation was assessed in the Safety Analysis Set.

Arm/Group Title	Quizartinib 30 mg	Quizartinib 60 mg
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.	Participants randomized to receive 60 mg quizartinib once daily.
Measure Participants	38	36
Max on study; <450 msec	47.4 124.7%	36.1 95%
Max on study; ≥450 msec and ≤480 msec	42.1 110.8%	47.2 124.2%
Max on study; >480 msec and ≤500 msec	5.3 13.9%	13.9 36.6%
Max on study; >500 msec	5.3 13.9%	2.8 7.4%
Max change from baseline; ≤30 msec	47.4 124.7%	38.9 102.4%
Max change from baseline; >30 msec and ≤60 msec	47.4 124.7%	41.7 109.7%
Max change from baseline; >60 msec	5.3 13.9%	19.4 51.1%

Adverse Events

Time Frame	Adverse event data were collected from the first dose of treatment up to 30 days from the last dose of treatment in the safety analysis set. Two participants in the quizartinib 60 mg cohort did not receive the study drug and were not included in the safety analysis set.
Arm/Group Title	Quizartinib 30 mg		Quizartinib 60 mg
Arm/Group Description	Participants randomized to receive 30 mg quizartinib once daily.		Participants randomized to receive 60 mg quizartinib once daily.
All Cause Mortality
	Quizartinib 30 mg		Quizartinib 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/38 (23.7%)		13/36 (36.1%)
Serious Adverse Events
	Quizartinib 30 mg		Quizartinib 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/38 (65.8%)		23/36 (63.9%)
Blood and lymphatic system disorders
Febrile neutropenia	7/38 (18.4%)		6/36 (16.7%)
Thrombocytopenia	2/38 (5.3%)		0/36 (0%)
Anemia	1/38 (2.6%)		0/36 (0%)
Disseminated intravascular coagulation	0/38 (0%)		1/36 (2.8%)
Febrile bone marrow aplasia	0/38 (0%)		1/36 (2.8%)
Leukocytosis	1/38 (2.6%)		0/36 (0%)
Pancytopenia	1/38 (2.6%)		0/36 (0%)
Cardiac disorders
Pericardial effusion	2/38 (5.3%)		1/36 (2.8%)
Atrial fibrillation	0/38 (0%)		1/36 (2.8%)
Bradycardia	1/38 (2.6%)		0/36 (0%)
Pericarditis	1/38 (2.6%)		0/36 (0%)
Tachycardia	1/38 (2.6%)		0/36 (0%)
Ventricular tachycardia	1/38 (2.6%)		0/36 (0%)
Gastrointestinal disorders
Nausea	0/38 (0%)		2/36 (5.6%)
Vomiting	0/38 (0%)		2/36 (5.6%)
Diarrhea	1/38 (2.6%)		1/36 (2.8%)
Gastrointestinal hemorrhage	2/38 (5.3%)		0/36 (0%)
Abdominal pain	1/38 (2.6%)		0/36 (0%)
Cecitis	1/38 (2.6%)		0/36 (0%)
Gastric ulcer	0/38 (0%)		1/36 (2.8%)
Hematemesis	1/38 (2.6%)		0/36 (0%)
Intestinal infarction	0/38 (0%)		1/36 (2.8%)
Lower gastrointestinal hemorrhage	1/38 (2.6%)		0/36 (0%)
Melaena	1/38 (2.6%)		0/36 (0%)
Oesophageal ulcer	1/38 (2.6%)		0/36 (0%)
Rectal hemorrhage	1/38 (2.6%)		0/36 (0%)
General disorders
Pyrexia	3/38 (7.9%)		5/36 (13.9%)
Multi-organ failure	0/38 (0%)		2/36 (5.6%)
Hyperthermia	1/38 (2.6%)		1/36 (2.8%)
Disease progression	0/38 (0%)		1/36 (2.8%)
Non-cardiac chest pain	0/38 (0%)		1/36 (2.8%)
Hepatobiliary disorders
Bile duct obstruction	0/38 (0%)		1/36 (2.8%)
Infections and infestations
Pneumonia	3/38 (7.9%)		6/36 (16.7%)
Cellulitis	1/38 (2.6%)		2/36 (5.6%)
Septic shock	1/38 (2.6%)		2/36 (5.6%)
Device-related infection	2/38 (5.3%)		0/36 (0%)
Periorbital cellulitis	2/38 (5.3%)		0/36 (0%)
Urinary tract infection bacterial	2/38 (5.3%)		0/36 (0%)
Clostridium difficile colitis	1/38 (2.6%)		1/36 (2.8%)
Sepsis	1/38 (2.6%)		1/36 (2.8%)
Abscess intestinal	1/38 (2.6%)		0/36 (0%)
Arthritis infective	0/38 (0%)		1/36 (2.8%)
Bacteremia	1/38 (2.6%)		0/36 (0%)
Bronchitis fungal	0/38 (0%)		1/36 (2.8%)
Candidiasis	0/38 (0%)		1/36 (2.8%)
Catheter-site infection	0/38 (0%)		1/36 (2.8%)
Clostridium difficile sepsis	0/38 (0%)		1/36 (2.8%)
Diverticulitis	1/38 (2.6%)		0/36 (0%)
Enteritis infectious	0/38 (0%)		1/36 (2.8%)
Escherichia sepsis	0/38 (0%)		1/36 (2.8%)
Klebsiella bacteremia	1/38 (2.6%)		0/36 (0%)
Lung infection	1/38 (2.6%)		0/36 (0%)
Neutropenic sepsis	1/38 (2.6%)		0/36 (0%)
Pneumonia fungal	0/38 (0%)		1/36 (2.8%)
Pneumonia respiratory syncytial viral	0/38 (0%)		1/36 (2.8%)
Sinusitis	0/38 (0%)		1/36 (2.8%)
Skin infection	0/38 (0%)		1/36 (2.8%)
Streptococcal infection	0/38 (0%)		1/36 (2.8%)
Urinary tract infection	1/38 (2.6%)		0/36 (0%)
Viral infection	1/38 (2.6%)		0/36 (0%)
Injury, poisoning and procedural complications
Accidental overdose	1/38 (2.6%)		0/36 (0%)
Investigations
Alanine aminotransferase increased	0/38 (0%)		2/36 (5.6%)
Electrocardiogram QT prolonged	0/38 (0%)		2/36 (5.6%)
Aspartate aminotransferase increased	0/38 (0%)		1/36 (2.8%)
Blood bilirubin increased	0/38 (0%)		1/36 (2.8%)
Medical observation	0/38 (0%)		1/36 (2.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/38 (2.6%)		0/36 (0%)
Muscular weakness	0/38 (0%)		1/36 (2.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukemia	5/38 (13.2%)		7/36 (19.4%)
Lung neoplasm	1/38 (2.6%)		0/36 (0%)
Neoplasm malignant	0/38 (0%)		1/36 (2.8%)
Nervous system disorders
Convulsion	0/38 (0%)		1/36 (2.8%)
Ischaemic stroke	0/38 (0%)		1/36 (2.8%)
Syncope	0/38 (0%)		1/36 (2.8%)
Psychiatric disorders
Mental status changes	1/38 (2.6%)		1/36 (2.8%)
Renal and urinary disorders
Renal failure acute	0/38 (0%)		2/36 (5.6%)
Urinary rentention	0/38 (0%)		2/36 (5.6%)
Hematuria	1/38 (2.6%)		0/36 (0%)
Reproductive system and breast disorders
Metrorrhagia	0/38 (0%)		1/36 (2.8%)
Respiratory, thoracic and mediastinal disorders
Hemoptysis	1/38 (2.6%)		1/36 (2.8%)
Pleural effusion	1/38 (2.6%)		1/36 (2.8%)
Acute pulmonary oedema	1/38 (2.6%)		0/36 (0%)
Cough	1/38 (2.6%)		0/36 (0%)
Dyspnoea	0/38 (0%)		1/36 (2.8%)
Lung disorder	0/38 (0%)		1/36 (2.8%)
Pneumonitis	0/38 (0%)		1/36 (2.8%)
Respiratory failure	0/38 (0%)		1/36 (2.8%)
Skin and subcutaneous tissue disorders
Erythema	1/38 (2.6%)		0/36 (0%)
Vascular disorders
Hypotension	1/38 (2.6%)		0/36 (0%)
Shock hemorrhagic	0/38 (0%)		1/36 (2.8%)
Venoocclusive disease	0/38 (0%)		1/36 (2.8%)
Other (Not Including Serious) Adverse Events
	Quizartinib 30 mg		Quizartinib 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/38 (97.4%)		36/36 (100%)
Blood and lymphatic system disorders
Anemia	18/38 (47.4%)		9/36 (25%)
Febrile neutropenia	12/38 (31.6%)		13/36 (36.1%)
Thrombocytopenia	10/38 (26.3%)		7/36 (19.4%)
Neutropenia	1/38 (2.6%)		5/36 (13.9%)
Leukocytosis	3/38 (7.9%)		1/36 (2.8%)
Cardiac disorders
Tachycardia	4/38 (10.5%)		6/36 (16.7%)
Pericardial effusion	3/38 (7.9%)		2/36 (5.6%)
Sinus tachycardia	1/38 (2.6%)		2/36 (5.6%)
Eye disorders
Vision blurred	3/38 (7.9%)		1/36 (2.8%)
Gastrointestinal disorders
Nausea	10/38 (26.3%)		17/36 (47.2%)
Vomiting	11/38 (28.9%)		13/36 (36.1%)
Diarrhea	10/38 (26.3%)		13/36 (36.1%)
Abdominal pain	6/38 (15.8%)		11/36 (30.6%)
Constipation	6/38 (15.8%)		3/36 (8.3%)
Dyspepsia	6/38 (15.8%)		2/36 (5.6%)
Hemorrhoids	2/38 (5.3%)		3/36 (8.3%)
Gastrointestinal hemorrhage	2/38 (5.3%)		1/36 (2.8%)
Hematemesis	1/38 (2.6%)		2/36 (5.6%)
Melaena	2/38 (5.3%)		1/36 (2.8%)
Proctalgia	1/38 (2.6%)		2/36 (5.6%)
Toothache	1/38 (2.6%)		2/36 (5.6%)
Abdominal discomfort	0/38 (0%)		2/36 (5.6%)
Abdominal pain upper	0/38 (0%)		2/36 (5.6%)
Eructation	2/38 (5.3%)		0/36 (0%)
Gastrooesophageal reflux disease	2/38 (5.3%)		0/36 (0%)
Mouth hemorrhage	0/38 (0%)		2/36 (5.6%)
General disorders
Pyrexia	11/38 (28.9%)		14/36 (38.9%)
Fatigue	13/38 (34.2%)		8/36 (22.2%)
Oedema peripheral	8/38 (21.1%)		6/36 (16.7%)
Mucosal inflammation	6/38 (15.8%)		5/36 (13.9%)
Chills	5/38 (13.2%)		3/36 (8.3%)
Pain	2/38 (5.3%)		4/36 (11.1%)
Asthenia	3/38 (7.9%)		2/36 (5.6%)
Non-cardiac chest pain	0/38 (0%)		5/36 (13.9%)
Oedema	1/38 (2.6%)		3/36 (8.3%)
Catheter site erythema	1/38 (2.6%)		2/36 (5.6%)
Catheter site pain	2/38 (5.3%)		1/36 (2.8%)
Chest discomfort	3/38 (7.9%)		0/36 (0%)
Malaise	0/38 (0%)		2/36 (5.6%)
Multi-organ failure	0/38 (0%)		2/36 (5.6%)
Infections and infestations
Pneumonia	3/38 (7.9%)		8/36 (22.2%)
Cellulitis	1/38 (2.6%)		3/36 (8.3%)
Clostridial infection	1/38 (2.6%)		3/36 (8.3%)
Clostridium difficile colitis	1/38 (2.6%)		2/36 (5.6%)
Herpes simplex	1/38 (2.6%)		2/36 (5.6%)
Rhinitis	1/38 (2.6%)		2/36 (5.6%)
Septic shock	1/38 (2.6%)		2/36 (5.6%)
Bacteremia	2/38 (5.3%)		0/36 (0%)
Bronchitis	0/38 (0%)		2/36 (5.6%)
Device related infection	2/38 (5.3%)		0/36 (0%)
Escherichia sepsis	0/38 (0%)		2/36 (5.6%)
Parainfluenzae virus infection	0/38 (0%)		2/36 (5.6%)
Periorbital cellulitis	2/38 (5.3%)		0/36 (0%)
Pneumonia fungal	0/38 (0%)		2/36 (5.6%)
Upper respiratory tract infection	0/38 (0%)		2/36 (5.6%)
Urinary tract infection	2/38 (5.3%)		0/36 (0%)
Urinary tract infection bacterial	2/38 (5.3%)		0/36 (0%)
Vaginal infection	2/38 (5.3%)		0/36 (0%)
Injury, poisoning and procedural complications
Contusion	3/38 (7.9%)		1/36 (2.8%)
Fall	1/38 (2.6%)		2/36 (5.6%)
Transfusion reaction	2/38 (5.3%)		1/36 (2.8%)
Procedural pain	0/38 (0%)		2/36 (5.6%)
Investigations
Alanine aminotransferase increased	3/38 (7.9%)		5/36 (13.9%)
Electrocardiogram QT prolonged	2/38 (5.3%)		6/36 (16.7%)
Blood bilirubin increased	3/38 (7.9%)		4/36 (11.1%)
Aspartate aminotransferase increased	2/38 (5.3%)		4/36 (11.1%)
Platelet count decreased	3/38 (7.9%)		1/36 (2.8%)
White blood cell count decreased	2/38 (5.3%)		1/36 (2.8%)
Blood alkaline phophatase increased	0/38 (0%)		2/36 (5.6%)
Metabolism and nutrition disorders
Hypokalemia	9/38 (23.7%)		6/36 (16.7%)
Decreased appetite	5/38 (13.2%)		6/36 (16.7%)
Hypomagnesemia	5/38 (13.2%)		4/36 (11.1%)
Hyperglycemia	4/38 (10.5%)		3/36 (8.3%)
Hyperphosphatemia	0/38 (0%)		6/36 (16.7%)
Hypoalbuminemia	4/38 (10.5%)		2/36 (5.6%)
Hypocalcemia	4/38 (10.5%)		2/36 (5.6%)
Hyponatremia	4/38 (10.5%)		2/36 (5.6%)
Hypophosphatemia	1/38 (2.6%)		5/36 (13.9%)
Hyperkalemia	2/38 (5.3%)		0/36 (0%)
Musculoskeletal and connective tissue disorders
Back pain	5/38 (13.2%)		3/36 (8.3%)
Musculoskeletal pain	2/38 (5.3%)		6/36 (16.7%)
Arthralgia	4/38 (10.5%)		2/36 (5.6%)
Pain in extremity	3/38 (7.9%)		3/36 (8.3%)
Myalgia	4/38 (10.5%)		1/36 (2.8%)
Neck pain	1/38 (2.6%)		4/36 (11.1%)
Muscular weakness	2/38 (5.3%)		2/36 (5.6%)
Musculoskeletal chest pain	2/38 (5.3%)		1/36 (2.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukemia	5/38 (13.2%)		7/36 (19.4%)
Nervous system disorders
Headache	4/38 (10.5%)		9/36 (25%)
Dysgeusia	6/38 (15.8%)		2/36 (5.6%)
Dizziness	3/38 (7.9%)		4/36 (11.1%)
Paresthesia	1/38 (2.6%)		3/36 (8.3%)
Tremor	2/38 (5.3%)		1/36 (2.8%)
Ageusia	0/38 (0%)		2/36 (5.6%)
Psychiatric disorders
Insomnia	2/38 (5.3%)		5/36 (13.9%)
Anxiety	1/38 (2.6%)		5/36 (13.9%)
Confusional state	1/38 (2.6%)		2/36 (5.6%)
Hallucination, visual	0/38 (0%)		2/36 (5.6%)
Renal and urinary disorders
Hematuria	1/38 (2.6%)		2/36 (5.6%)
Renal failure acute	0/38 (0%)		3/36 (8.3%)
Urinary retention	1/38 (2.6%)		2/36 (5.6%)
Urinary hesitation	0/38 (0%)		2/36 (5.6%)
Urinary incontinence	2/38 (5.3%)		0/36 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	9/38 (23.7%)		9/36 (25%)
Dyspnoea	8/38 (21.1%)		6/36 (16.7%)
Oropharyngeal pain	5/38 (13.2%)		6/36 (16.7%)
Epistaxis	6/38 (15.8%)		4/36 (11.1%)
Pleural effusion	3/38 (7.9%)		4/36 (11.1%)
Nasal congestion	2/38 (5.3%)		2/36 (5.6%)
Hemoptysis	2/38 (5.3%)		1/36 (2.8%)
Productive cough	2/38 (5.3%)		1/36 (2.8%)
Rhinorrhea	3/38 (7.9%)		0/36 (0%)
Dyspnoea exertional	2/38 (5.3%)		0/36 (0%)
Lung disorder	0/38 (0%)		2/36 (5.6%)
Sinus congestion	2/38 (5.3%)		0/36 (0%)
Skin and subcutaneous tissue disorders
Erythema	1/38 (2.6%)		4/36 (11.1%)
Skin lesion	3/38 (7.9%)		2/36 (5.6%)
Dry skin	3/38 (7.9%)		1/36 (2.8%)
Petechiae	1/38 (2.6%)		3/36 (8.3%)
Rash	1/38 (2.6%)		3/36 (8.3%)
Pruritus	3/38 (7.9%)		0/36 (0%)
Rash erythematous	2/38 (5.3%)		1/36 (2.8%)
Rash maculo-papular	2/38 (5.3%)		1/36 (2.8%)
Night sweats	2/38 (5.3%)		0/36 (0%)
Vascular disorders
Hypotension	6/38 (15.8%)		4/36 (11.1%)
Hypertension	1/38 (2.6%)		3/36 (8.3%)
Thrombophlebitis superficial	2/38 (5.3%)		0/36 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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