A Phase I Study of AC220 in Patients With Relapsed/Refractory Acute Myeloid Leukemia Regardless of FLT3 Status

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00462761
• Collaborator: (none)
• Enrollment: 76
• Locations: 5
• Arm: 1
• Duration (Months): 35
• Patients Per Site: 15.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Patients received oral AC220 daily for 14 days to study the side effects, tolerability and best dose for treating relapsed or refractory acute myeloid leukemia, regardless of FLT3 status.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Leukemia; Myelodysplastic Syndrome; AML; MDS	Drug: AC220	Phase 1

Detailed Description

This is a multi-center clinical study conducted in the USA and two international sites. This open-label, dose escalation study was designed to characterize the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered AC220 as a single agent given daily for 14 days. Cohorts of 3 patients received AC220 until dose limiting toxicity was noted (DLT). At that point cohorts expanded to 6 patients until MTD was determined. Patients not experiencing DLT or significant disease progression at Day 15 may have continued receiving AC220 at the discretion of the Investigator and Sponsor. FLT3 positive and negative patients were allowed to participate.

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Open-Label, Sequential Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AC220 When Administered Daily to Patients With Relapsed or Refractory Acute Myeloid Leukemia
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AC220 Determine safety, tolerability and pharmacokinetic (PK) parameters of AC220	Drug: AC220; Powder in bottle formulation supplied as 50mg or 350 mg in glass, crimped serum vials. Requires reconstitution by a pharmacist, and must be stored securely and protected from light.; Other Names: Quizartinib

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Treatment Related Adverse Events Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia [Baseline up to 30 days post last dose]

2. Number of Participants With Treatment-emergent Treatment-related Grade 3 or 4 Adverse Events By At Least 10% of All Participants By Dose Group Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia [Baseline up to 30 days post last dose]

Secondary Outcome Measures

1. Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Progressive Disease Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia [Baseline up to 28 days after the last dose, up to approximately 3 years]

   Progressive disease response criteria included doubling of blast count % in bone marrow (biopsy or aspirate) from baseline; considering measurements starting on Study Day 15, doubling of blast count % in blood from baseline; death determined to be related to disease or disease progression; and investigator reported disease progression.

2. Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Best Overall Response Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia [Baseline up to 28 days after the last dose, up to approximately 3 years]

   Complete Response (CR) response criteria included either a post-baseline bone marrow (BM) biopsy or aspiration % blasts <5%, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L on the same date as the qualifying BM assessment. CRp response included all CR criteria met, except participant did not experience a platelet recovery (ANC recovery required). CRi response included a qualifying BM result, but not an ANC recovery. Participants may or may not have had a platelet recovery and were not required to be transfusion independent. Partial remission (PR) response included a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline to a post-baseline result between 5% to 25% in the bone marrow aspirate or biopsy. Nonresponders (NR) had a pre- and 1 or more post-baseline BM assessment carried out, but results did not meet any response criteria. Participants who were not evaluable (NE) did not have at least 14 days of treatment and were not assessed.

3. Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Best Overall Response Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia [Baseline up to 28 days after the last dose, up to approximately 3 years]

   Complete Response (CR) response criteria included either a post-baseline bone marrow biopsy or aspiration % blasts <5%, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L on the same date as the qualifying bone marrow assessment. CRp response included all CR criteria met except participant did not experience a platelet recovery. Participants must have experienced an ANC Recovery. CRi response included a qualifying bone marrow result, but did not experience an ANC recovery. Participants may or may not have experienced a platelet recovery and were not required to be transfusion independent. Partial remission (PR) response included a decrease of ≥50% in % blasts in the bone marrow aspirate or biopsy from baseline to a post-baseline result between 5% to 25% in the bone marrow aspirate or biopsy. Nonresponders (NR) had a pre- and 1 or more post-baseline bone marrow assessment carried out, but results did not meet any of the CR or PR or progressive disease criteria.

4. Number of Participants With Hematologic Improvement Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia [Baseline up to 28 days after the last dose, up to approximately 3 years]

   Hematologic improvement is summarized in terms of Erythroid Response (HI-E), Platelet Response (HI-P), Neutrophil Response (HI-N), and Hematologic Improvement (HI). For post-treatment results, HI-E major responders had >2 g/dL increase in hemoglobin for at least 1 result after first treatment and transfusion independent; minor responders 1 to 2 g/dL increase in hemoglobin for at least 1 result post first treatment and a 50% decrease in red blood cell transfusion requirements. For HI-P, major responders had ≥30 × 10^9/L increase in platelet count and transfusion independent; minor responders had 50% or more increase in platelet count with a net increase between 10 to 30 × 10^9/L and 50% decrease in platelet transfusion requirements. For HI-N, major responders had an increase in absolute neutrophil count (ANC) of 100% or an absolute increase of more than 0.5 × 10^9/L (whichever is greater); minor responders had an increase in ANC of 100% but an absolute increase of <0.5 × 10^9/L.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Males and females age ≥ 18 years;

2. Histopathologically documented primary or secondary AML, as defined by WHO criteria (Jaffe et al, 2001), confirmed by pathology review at treating institution, meeting at least one of the following:

3. Refractory to at least 1 cycle of induction chemotherapy, or

4. Relapsed after at least 1 cycle of induction chemotherapy, or

5. Patient is not, according to the clinical judgment of the Principal Investigator, a candidate for induction chemotherapy due to age, comorbidity, or other factors;

6. Patients for whom no standard therapies are anticipated to result in a durable remission, or who have failed potentially curative therapy, or who refuse standard therapy or patients for whom there is no known therapy of documented treatment benefit;

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;

8. In the absence of rapidly progressing disease, the interval from prior treatment to time of AC220 administration should be at least 2 weeks for cytotoxic agents (other than hydroxyurea, per Section 8.8), or at least 5 half-lives for noncytotoxic agents;

9. Persistent chronic clinically significant toxicities from prior chemotherapy or surgery must be less than Grade 2;

10. Serum creatinine ≤ 2.0 mg/dL;

11. Total serum bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's syndrome or leukemic organ involvement;

12. Serum AST or ALT ≤ 3.0 × ULN unless considered due to leukemic organ involvement;

13. Females of childbearing potential must have a negative pregnancy test (urine β-hCG);

14. Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study;

15. Written informed consent must be provided.

Exclusion Criteria:

1. Histologic diagnosis of acute promyelocytic leukemia;

2. Clinically active central nervous system leukemia;

3. Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3);

4. Bone marrow transplant within 2 months prior to study;

5. Active, uncontrolled infection;

6. Major surgery within 4 weeks prior to study;

7. Radiation therapy within 4 weeks prior to, or concurrent with, study;

8. Human immunodeficiency virus positivity;

9. Active hepatitis B or C or other active liver disease;

10. Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential;

11. Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize patient safety or interfere with the objectives of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
3	MD Anderson Cancer Center	Houston	Texas	United States	77030
4	Chemotherapy and Immunotherapy Clinic	T'Bilisi		Georgia
5	Hematology and Chemotherapy Clinic	T'bilisi		Georgia

Sponsors and Collaborators

• Daiichi Sankyo, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT00462761
• Other Study ID Numbers: CP0001
• First Posted: Apr 19, 2007
• Last Update Posted: May 11, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Daiichi Sankyo, Inc.: RTK; kinase; inhibitor; tyrosine; acute; FLT3; AC220; pharmacokinetic; pharmacokinetics; PK; pharmacodynamic; pharmacodynamics; mutations; PD; receptor; class III; relapsed; refractory; t(8;21); q22;q22; AML1/ETO; t(16;16; p13;q22; CBFbeta/MYH11; inv(16); p13q22; 11q23; dysplasia; myeloid; myelomonocytic; monoblastic; monocytic; erythroid; erythroleukemia; megakaryoblastic; basophilic; panmyelosis; myelofibrosis
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Study Results

Participant Flow

Recruitment Details	A total of 76 participants who met all inclusion and no exclusion criteria were enrolled and treated in the study at 4 clinical sites in the United States and 2 sites in the Republic of Georgia.

Arm/Group Title	Quizartinib
Arm/Group Description	Participants initially received quizartinib (AC220) on an intermittent dosing (ID) schedule (14 days on treatment followed by 14 days off treatment) up to a maximum of 200 mg/day. Following a protocol amendment, participants then received a starting dose of 300 mg/day quizartinib on an ID regimen or received a starting dose of 200 mg/day quizartinib for 28 days (1 cycle) on a continuous dosing schedule.
Period Title: Overall Study
STARTED	76
COMPLETED	0
NOT COMPLETED	76

Baseline Characteristics

Arm/Group Title	Quizartinib
Arm/Group Description	Participants initially received quizartinib (AC220) on an intermittent dosing (ID) schedule (14 days on treatment followed by 14 days off treatment) up to a maximum of 200 mg/day. Following a protocol amendment, participants then received a starting dose of 300 mg/day quizartinib on an ID regimen or received a starting dose of 200 mg/day quizartinib for 28 days (1 cycle) on a continuous dosing schedule.
Overall Participants	76
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.0 (17.1)
Age, Customized (Count of Participants)
<18 years	0 0%
18 to 60 years	39 51.3%
61 to 75 years	31 40.8%
>75 years	6 7.9%
Sex: Female, Male (Count of Participants)
Female	30 39.5%
Male	46 60.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 2.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 7.9%
White	68 89.5%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Treatment Related Adverse Events Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Time Frame	Baseline up to 30 days post last dose

Outcome Measure Data

Analysis Population Description

Safety events were assessed in the Safety Population.

Arm/Group Title	Quizartinib
Arm/Group Description	Participants initially received quizartinib (AC220) on an intermittent dosing (ID) schedule (14 days on treatment followed by 14 days off treatment) up to a maximum of 200 mg/day. Following a protocol amendment, participants then received a starting dose of 300 mg/day quizartinib on an ID regimen or received a starting dose of 200 mg/day quizartinib for 28 days (1 cycle) on a continuous dosing schedule.
Measure Participants	76
At Least 1 Treatment-Related Adverse Event	39 51.3%
General disorders & administration site conditions	11 14.5%
Pyrexia	2 2.6%
Fatigue	4 5.3%
Oedema peripheral	6 7.9%
Asthenia	1 1.3%
Chills	1 1.3%
Malaise	1 1.3%
Gastrointestinal disorders	21 27.6%
Nausea	12 15.8%
Diarrhoea	6 7.9%
Vomiting	8 10.5%
Abdominal pain	3 3.9%
Abdominal pain upper	2 2.6%
Dyspepsia	3 3.9%
Constipation	1 1.3%
Abdominal distension	2 2.6%
Gastrointestinal haemorrhage	1 1.3%
Gastrooesophageal reflux disease	1 1.3%
Abdominal discomfort	1 1.3%
Oral mucosal blistering	1 1.3%
Epigastric discomfort	1 1.3%
Retching	1 1.3%
Respiratory, Thoracic, and Mediastinal Disorders	2 2.6%
Haemoptysis	1 1.3%
Dyspnoea exertional	1 1.3%
Blood and Lymphatic System Disorders	4 5.3%
Anaemia	3 3.9%
Thrombocytopenia	1 1.3%
Pancytopenia	1 1.3%
Skin and Subcutaneous Tissue Disorders	8 10.5%
Periorbital odema	1 1.3%
Swelling face	1 1.3%
Alopecia	2 2.6%
Dry skin	1 1.3%
Increased tendency to bruise	1 1.3%
Hair colour changes	1 1.3%
Hidradenitis	1 1.3%
Photosensitivity reaction	1 1.3%
Infections and Infestations	1 1.3%
Pneumonia	1 1.3%
Lung infection	1 1.3%
Metabolism and Nutrition Disorders	7 9.2%
Hypokalaemia	2 2.6%
Anorexia	5 6.6%
Hyperglycaemia	1 1.3%
Hypoalbuminaemia	1 1.3%
Nervous System Disorders	12 15.8%
Headache	2 2.6%
Dizziness	1 1.3%
Dysgeusia	8 10.5%
Hypoaesthesia	1 1.3%
Neuropathy peripheral	1 1.3%
Dysarthria	1 1.3%
Investigations	11 14.5%
Electrocardiogram QT prolonged	9 11.8%
Blood bilirubin increased	1 1.3%
Hepatic enzyme increased	1 1.3%
Psychiatric Disorders	1 1.3%
Insomnia	1 1.3%
Cardiac Disorders	1 1.3%
Right ventricular dysfunction	1 1.3%
Injury, Poisoning, and Procedural Complications	1 1.3%
Contusion	1 1.3%
Eye Disorders	1 1.3%
Eyelid oedema	1 1.3%
Hepatobiliary Disorders	3 3.9%
Hyperbilirubinaemia	3 3.9%
Jaundice	1 1.3%

2. Primary Outcome

Title	Number of Participants With Treatment-emergent Treatment-related Grade 3 or 4 Adverse Events By At Least 10% of All Participants By Dose Group Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Time Frame	Baseline up to 30 days post last dose

Outcome Measure Data

Analysis Population Description

Safety events were assessed in the Safety Population.

Arm/Group Title	Quizartinib 12-135 mg ID	Quizartinib 200-450 mg ID	Quizartinib 200-300 mg CD	Total
Arm/Group Description	Participants received quizartinib (AC220) with doses ranging from 12-135 mg on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) with doses ranging from 200-450 mg on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) with doses ranging from 200-300 mg on a continuous dosing (CD) schedule.	All participants who received quizartinib, regardless of dosage or dosing schedule.
Measure Participants	35	16	25	76
Nausea : All Grades	6 7.9%	3 NaN	3 NaN	12 NaN
Nausea : Grade 3-4	0 0%	0 NaN	0 NaN	0 NaN
Electrocardiogram QT prolonged : All Grades	1 1.3%	0 NaN	8 NaN	9 NaN
Electrocardiogram QT prolonged : Grade 3-4	0 0%	0 NaN	4 NaN	4 NaN
Dysgeusia : All Grades	4 5.3%	1 NaN	3 NaN	8 NaN
Dysgeusia : Grade 3-4	0 0%	0 NaN	0 NaN	0 NaN
Vomiting : All Grades	3 3.9%	3 NaN	2 NaN	8 NaN
Vomiting : Grade 3-4	1 1.3%	0 NaN	0 NaN	1 NaN
Anorexia : All Grades	3 3.9%	1 NaN	1 NaN	5 NaN
Anorexia : Grade 3-4	1 1.3%	0 NaN	0 NaN	1 NaN
Fatigue : All Grades	2 2.6%	1 NaN	1 NaN	4 NaN
Fatigue : Grade 3-4	1 1.3%	0 NaN	1 NaN	2 NaN
Anaemia : All Grades	2 2.6%	1 NaN	0 NaN	3 NaN
Anaemia : Grade 3-4	2 2.6%	1 NaN	0 NaN	3 NaN
Hypokalaemia : All Grades	2 2.6%	0 NaN	0 NaN	2 NaN
Hypokalaemia : Grade 3-4	1 1.3%	0 NaN	0 NaN	1 NaN
Pyrexia : All Grades	2 2.6%	0 NaN	0 NaN	2 NaN
Pyrexia : Grade 3-4	1 1.3%	0 NaN	0 NaN	1 NaN
Eyelid oedema : All Grades	0 0%	1 NaN	0 NaN	1 NaN
Eyelid oedema : Grade 3-4	0 0%	1 NaN	0 NaN	1 NaN
Hypoalbuminaemia : All Grades	0 0%	1 NaN	0 NaN	1 NaN
Hypoalbuminaemia : Grade 3-4	0 0%	1 NaN	0 NaN	1 NaN
Lung infection : All Grades	0 0%	1 NaN	0 NaN	1 NaN
Lung infection : Grade 3-4	0 0%	1 NaN	0 NaN	1 NaN
Pancytopenia : All Grades	1 1.3%	0 NaN	0 NaN	1 NaN
Pancytopenia : Grade 3-4	1 1.3%	0 NaN	0 NaN	1 NaN
Photosensitivity reaction : All Grades	0 0%	0 NaN	1 NaN	1 NaN
Photosensitivity reaction : Grade 3-4	0 0%	0 NaN	1 NaN	1 NaN
Thrombocytopenia : All Grades	0 0%	0 NaN	1 NaN	1 NaN
Thrombocytopenia : Grade 3-4	0 0%	0 NaN	1 NaN	1 NaN

3. Secondary Outcome

Title	Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Progressive Disease Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Description	Progressive disease response criteria included doubling of blast count % in bone marrow (biopsy or aspirate) from baseline; considering measurements starting on Study Day 15, doubling of blast count % in blood from baseline; death determined to be related to disease or disease progression; and investigator reported disease progression.
Time Frame	Baseline up to 28 days after the last dose, up to approximately 3 years

Outcome Measure Data

Analysis Population Description

Disease response was assessed in the Intent-to-Treat Population.

Arm/Group Title	Quizartinib 12 mg ID	Quizartinib 18 mg ID	Quizartinib 27 mg ID	Quizartinib 40 mg ID	Quizartinib 60 mg ID	Quizartinib 90 mg ID	Quizartinib 135 mg ID	Quizartinib 200 mg ID	Quizartinib 300 mg ID	Quizartinib 450 mg ID	Quizartinib 200 mg CD	Quizartinib 300 mg CD	All Participants
Arm/Group Description	Participants received quizartinib (AC220) 12 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 18 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 27 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 40 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 60 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 90 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 135 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 200 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 300 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 450 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 200 mg/day on a continuous dosing (CD) schedule.	Participants received quizartinib (AC220) 300 mg/day on a continuous dosing (CD) schedule.	All participants who received quizartinib, regardless of dosage and dosing schedule.
Measure Participants	3	8	6	5	5	3	5	6	4	6	17	8	76
Count of Participants [Participants]	2 2.6%	2 NaN	3 NaN	3 NaN	2 NaN	1 NaN	1 NaN	1 NaN	2 NaN	2 NaN	4 NaN	3 NaN	26 NaN

4. Secondary Outcome

Title	Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Best Overall Response Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Description	Complete Response (CR) response criteria included either a post-baseline bone marrow (BM) biopsy or aspiration % blasts <5%, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L on the same date as the qualifying BM assessment. CRp response included all CR criteria met, except participant did not experience a platelet recovery (ANC recovery required). CRi response included a qualifying BM result, but not an ANC recovery. Participants may or may not have had a platelet recovery and were not required to be transfusion independent. Partial remission (PR) response included a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline to a post-baseline result between 5% to 25% in the bone marrow aspirate or biopsy. Nonresponders (NR) had a pre- and 1 or more post-baseline BM assessment carried out, but results did not meet any response criteria. Participants who were not evaluable (NE) did not have at least 14 days of treatment and were not assessed.
Time Frame	Baseline up to 28 days after the last dose, up to approximately 3 years

Outcome Measure Data

Analysis Population Description

Disease response was assessed in the Intent-to-Treat Population.

Arm/Group Title	Quizartinib 12 mg ID	Quizartinib 18 mg ID	Quizartinib 27 mg ID	Quizartinib 40 mg ID	Quizartinib 60 mg ID	Quizartinib 90 mg ID	Quizartinib 135 mg ID	Quizartinib 200 mg ID	Quizartinib 300 mg ID	Quizartinib 450 mg ID	Quizartinib 200 mg CD	Quizartinib 300 mg CD	All Participants
Arm/Group Description	Participants received quizartinib (AC220) 12 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 18 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 27 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 40 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 60 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 90 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 135 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 200 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 300 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 450 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 200 mg/day on a continuous dosing (CD) schedule.	Participants received quizartinib (AC220) 300 mg/day on a continuous dosing (CD) schedule.	All participants who received quizartinib, regardless of dosage and dosing schedule.
Measure Participants	3	8	6	5	5	3	5	6	4	6	17	8	76
Overall response	0 0%	1 NaN	2 NaN	2 NaN	2 NaN	1 NaN	1 NaN	2 NaN	2 NaN	2 NaN	6 NaN	2 NaN	23 NaN
composite CR (CR+CRp+CRi)	0 0%	0 NaN	0 NaN	1 NaN	1 NaN	0 NaN	0 NaN	1 NaN	1 NaN	0 NaN	5 NaN	1 NaN	10 NaN
Complete response (CR)	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	2 NaN	0 NaN	2 NaN
CR with incomplete platelet recovery	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	1 NaN	0 NaN	3 NaN
CR with incomplete hematologic recovery	0 0%	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	2 NaN	1 NaN	5 NaN
Partial remission (PR)	0 0%	1 NaN	2 NaN	1 NaN	1 NaN	1 NaN	1 NaN	1 NaN	1 NaN	2 NaN	1 NaN	1 NaN	13 NaN
Nonresponder (NR)	1 1.3%	2 NaN	0 NaN	0 NaN	1 NaN	1 NaN	2 NaN	3 NaN	0 NaN	2 NaN	5 NaN	2 NaN	19 NaN
Not evaluable (NE)	0 0%	3 NaN	1 NaN	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	2 NaN	1 NaN	8 NaN

5. Secondary Outcome

Title	Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Progressive Disease Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Description	Progressive disease response criteria included doubling of blast count % in bone marrow (biopsy or aspirate) from baseline; considering measurements starting on Study Day 15, doubling of blast count % in blood from baseline; death determined to be related to disease or disease progression; and investigator reported disease progression.
Time Frame	Baseline up to 28 days after the last dose, up to approximately 3 years

Outcome Measure Data

Analysis Population Description

Disease response was assessed in the Evaluable Population.

Arm/Group Title	Quizartinib 12 mg ID	Quizartinib 18 mg ID	Quizartinib 27 mg ID	Quizartinib 40 mg ID	Quizartinib 60 mg ID	Quizartinib 90 mg ID	Quizartinib 135 mg ID	Quizartinib 200 mg ID	Quizartinib 300 mg ID	Quizartinib 450 mg ID	Quizartinib 200 mg CD	Quizartinib 300 mg CD	All Participants
Arm/Group Description	Participants received quizartinib (AC220) 12 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 18 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 27 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 40 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 60 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 90 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 135 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 200 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 300 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 450 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 200 mg/day on a continuous dosing (CD) schedule.	Participants received quizartinib (AC220) 300 mg/day on a continuous dosing (CD) schedule.	All participants who received quizartinib, regardless of dosage and dosing schedule.
Measure Participants	3	5	4	4	5	2	4	5	4	4	12	7	59
Count of Participants [Participants]	2 2.6%	2 NaN	2 NaN	2 NaN	2 NaN	0 NaN	1 NaN	0 NaN	2 NaN	1 NaN	1 NaN	3 NaN	18 NaN

6. Secondary Outcome

Title	Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Best Overall Response Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Description	Complete Response (CR) response criteria included either a post-baseline bone marrow biopsy or aspiration % blasts <5%, absolute neutrophil count (ANC) >1×10^9/L and platelet count >100×10^9/L on the same date as the qualifying bone marrow assessment. CRp response included all CR criteria met except participant did not experience a platelet recovery. Participants must have experienced an ANC Recovery. CRi response included a qualifying bone marrow result, but did not experience an ANC recovery. Participants may or may not have experienced a platelet recovery and were not required to be transfusion independent. Partial remission (PR) response included a decrease of ≥50% in % blasts in the bone marrow aspirate or biopsy from baseline to a post-baseline result between 5% to 25% in the bone marrow aspirate or biopsy. Nonresponders (NR) had a pre- and 1 or more post-baseline bone marrow assessment carried out, but results did not meet any of the CR or PR or progressive disease criteria.
Time Frame	Baseline up to 28 days after the last dose, up to approximately 3 years

Outcome Measure Data

Analysis Population Description

Disease response was assessed in the Evaluable Population.

Arm/Group Title	Quizartinib 12 mg ID	Quizartinib 18 mg ID	Quizartinib 27 mg ID	Quizartinib 40 mg ID	Quizartinib 60 mg ID	Quizartinib 90 mg ID	Quizartinib 135 mg ID	Quizartinib 200 mg ID	Quizartinib 300 mg ID	Quizartinib 450 mg ID	Quizartinib 200 mg CD	Quizartinib 300 mg CD	All Participants
Arm/Group Description	Participants received quizartinib (AC220) 12 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 18 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 27 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 40 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 60 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 90 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 135 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 200 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 300 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 450 mg/day on an intermittent dosing (ID) schedule.	Participants received quizartinib (AC220) 200 mg/day on a continuous dosing (CD) schedule.	Participants received quizartinib (AC220) 300 mg/day on a continuous dosing (CD) schedule.	All participants who received quizartinib, regardless of dosage and dosing schedule.
Measure Participants	3	5	4	4	5	2	4	5	4	4	12	7	59
Overall response	0 0%	1 NaN	2 NaN	2 NaN	2 NaN	1 NaN	1 NaN	2 NaN	2 NaN	1 NaN	6 NaN	2 NaN	22 NaN
Composite CR (CR+CRp+CRi)	0 0%	0 NaN	0 NaN	1 NaN	1 NaN	0 NaN	0 NaN	1 NaN	1 NaN	0 NaN	5 NaN	1 NaN	10 NaN
Complete response (CR)	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	2 NaN	0 NaN	2 NaN
CR with incomplete platelet recovery	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	1 NaN	0 NaN	3 NaN
CR with incomplete hematologic recovery	0 0%	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	0 NaN	0 NaN	1 NaN	0 NaN	2 NaN	1 NaN	5 NaN
Partial remission	0 0%	1 NaN	2 NaN	1 NaN	1 NaN	1 NaN	1 NaN	1 NaN	1 NaN	1 NaN	1 NaN	1 NaN	12 NaN
Nonresponder	1 1.3%	2 NaN	0 NaN	0 NaN	1 NaN	1 NaN	2 NaN	3 NaN	0 NaN	2 NaN	5 NaN	2 NaN	19 NaN

7. Secondary Outcome

Title	Number of Participants With Hematologic Improvement Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Description	Hematologic improvement is summarized in terms of Erythroid Response (HI-E), Platelet Response (HI-P), Neutrophil Response (HI-N), and Hematologic Improvement (HI). For post-treatment results, HI-E major responders had >2 g/dL increase in hemoglobin for at least 1 result after first treatment and transfusion independent; minor responders 1 to 2 g/dL increase in hemoglobin for at least 1 result post first treatment and a 50% decrease in red blood cell transfusion requirements. For HI-P, major responders had ≥30 × 10^9/L increase in platelet count and transfusion independent; minor responders had 50% or more increase in platelet count with a net increase between 10 to 30 × 10^9/L and 50% decrease in platelet transfusion requirements. For HI-N, major responders had an increase in absolute neutrophil count (ANC) of 100% or an absolute increase of more than 0.5 × 10^9/L (whichever is greater); minor responders had an increase in ANC of 100% but an absolute increase of <0.5 × 10^9/L.
Time Frame	Baseline up to 28 days after the last dose, up to approximately 3 years

Outcome Measure Data

Analysis Population Description

Hematologic improvement was assessed in the Intent-to-Treat Population.

Arm/Group Title	Quizartinib
Arm/Group Description	Participants initially received quizartinib (AC220) on an intermittent dosing (ID) schedule (14 days on treatment followed by 14 days off treatment) up to a maximum of 200 mg/day. Following a protocol amendment, participants then received a starting dose of 300 mg/day quizartinib on an ID regimen or received a starting dose of 200 mg/day quizartinib for 28 days (1 cycle) on a continuous dosing schedule.
Measure Participants	76
Erythroid Response (HI-E) Responders	35 46.1%
Erythroid Response (HI-E) Major Responders	15 19.7%
Erythroid Response (HI-E) Minor Responders	20 26.3%
Erythroid Response (HI-E) No Response	34 44.7%
HI-E Participants excluded	7 9.2%
Platelet Response (HI-P) Responders	39 51.3%
Platelet Response (HI-P) Major Responders	18 23.7%
Platelet Response (HI-P) Minor Responders	21 27.6%
Platelet Response (HI-P) No Response	29 38.2%
HI-P Participants excluded	8 10.5%
Neutrophil Response (HI-N) Responders	26 34.2%
Neutrophil Response (HI-N) Major Responders	19 25%
Neutrophil Response (HI-N) Minor Responders	7 9.2%
Neutrophil Response (HI-N) No Response	24 31.6%
HI-N Participants excluded	26 34.2%
Hematologic Improvement (HI) Responders	60 78.9%
Hematologic Improvement (HI) Any Major Response	38 50%
Hematologic Improvement (HI) Any Minor Response	22 28.9%
HI Participants excluded	1 1.3%

Adverse Events

Time Frame	Adverse events were collected from after initiation of study drug up to 30 days after last dose, up to approximately 3 years.
Arm/Group Title	Quizartinib 12 mg ID		Quizartinib 18 mg ID		Quizartinib 27 mg ID		Quizartinib 40 mg ID		Quizartinib 60 mg ID		Quizartinib 90 mg ID		Quizartinib 135 mg ID		Quizartinib 200 mg ID		Quizartinib 300 mg ID		Quizartinib 450 mg ID		Quizartinib 200 mg CD		Quizartinib 300 mg CD
Arm/Group Description	Participants received quizartinib (AC220) 12 mg/day on an intermittent dosing (ID) schedule.		Participants received quizartinib (AC220) 18 mg/day on an intermittent dosing (ID) schedule.		Participants received quizartinib (AC220) 27 mg/day on an intermittent dosing (ID) schedule.		Participants received quizartinib (AC220) 40 mg/day on an intermittent dosing (ID) schedule.		Participants received quizartinib (AC220) 60 mg/day on an intermittent dosing (ID) schedule.		Participants received quizartinib (AC220) 90 mg/day on an intermittent dosing (ID) schedule.		Participants received quizartinib (AC220) 135 mg/day on an intermittent dosing (ID) schedule.		Participants received quizartinib (AC220) 200 mg/day on an intermittent dosing (ID) schedule.		Participants received quizartinib (AC220) 300 mg/day on an intermittent dosing (ID) schedule.		Participants received quizartinib (AC220) 450 mg/day on an intermittent dosing (ID) schedule.		Participants received quizartinib (AC220) 200 mg/day on a continuous dosing (CD) schedule.		Participants received quizartinib (AC220) 300 mg/day on a continuous dosing (CD) schedule.
All Cause Mortality
	Quizartinib 12 mg ID		Quizartinib 18 mg ID		Quizartinib 27 mg ID		Quizartinib 40 mg ID		Quizartinib 60 mg ID		Quizartinib 90 mg ID		Quizartinib 135 mg ID		Quizartinib 200 mg ID		Quizartinib 300 mg ID		Quizartinib 450 mg ID		Quizartinib 200 mg CD		Quizartinib 300 mg CD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		8/8 (100%)		6/6 (100%)		5/5 (100%)		5/5 (100%)		3/3 (100%)		5/5 (100%)		5/6 (83.3%)		4/4 (100%)		6/6 (100%)		16/17 (94.1%)		8/8 (100%)
Serious Adverse Events
	Quizartinib 12 mg ID		Quizartinib 18 mg ID		Quizartinib 27 mg ID		Quizartinib 40 mg ID		Quizartinib 60 mg ID		Quizartinib 90 mg ID		Quizartinib 135 mg ID		Quizartinib 200 mg ID		Quizartinib 300 mg ID		Quizartinib 450 mg ID		Quizartinib 200 mg CD		Quizartinib 300 mg CD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		4/8 (50%)		1/6 (16.7%)		3/5 (60%)		4/5 (80%)		2/3 (66.7%)		4/5 (80%)		3/6 (50%)		3/4 (75%)		5/6 (83.3%)		9/17 (52.9%)		8/8 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	0/3 (0%)		0/8 (0%)		0/6 (0%)		2/5 (40%)		0/5 (0%)		1/3 (33.3%)		2/5 (40%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		1/8 (12.5%)
Thrombocytopenia	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/17 (5.9%)		1/8 (12.5%)
Anaemia	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Neutropenia	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		1/8 (12.5%)
Cardiac disorders
Atrial fibrillation	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Cardiac failure	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Cardiac failure congestive	0/3 (0%)		1/8 (12.5%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Cardio-respiratory arrest	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Gastrointestinal disorders
Abdominal pain	1/3 (33.3%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Melaena	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		1/8 (12.5%)
Vomiting	1/3 (33.3%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Colitis	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Gastrointestinal haemorrrhage	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/17 (5.9%)		0/8 (0%)
Ileus	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Mallory-Weiss syndrome	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/17 (0%)		0/8 (0%)
Nausea	1/3 (33.3%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Rectal haemorrhage	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/17 (0%)		0/8 (0%)
Upper gastrointestinal haemorrhage	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		1/8 (12.5%)
General disorders
Disease progression	0/3 (0%)		2/8 (25%)		0/6 (0%)		1/5 (20%)		4/5 (80%)		1/3 (33.3%)		1/5 (20%)		2/6 (33.3%)		1/4 (25%)		4/6 (66.7%)		5/17 (29.4%)		3/8 (37.5%)
Fatigue	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		1/8 (12.5%)
Pyrexia	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Infections and infestations
Pneumonia	0/3 (0%)		0/8 (0%)		1/6 (16.7%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		1/8 (12.5%)
Neutropenic sepsis	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Abscess neck	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		1/8 (12.5%)
Bronchitis	0/3 (0%)		1/8 (12.5%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Creutzfeldt-Jakob disease	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/17 (5.9%)		0/8 (0%)
Diverticulitis	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/17 (5.9%)		0/8 (0%)
Gastrointestinal fungal infection	1/3 (33.3%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Lung infection	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Neutropenic infection	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Sepsis	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/17 (5.9%)		0/8 (0%)
Sinusitis	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		1/8 (12.5%)
Sinusitis fungal	0/3 (0%)		0/8 (0%)		0/6 (0%)		1/5 (20%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Staphylococcal bacteraemia	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Injury, poisoning and procedural complications
Subdural haemtoma	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Investigations
Electrocardiogram QT prolonged	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/17 (5.9%)		2/8 (25%)
Haemoglobin decreased	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/17 (0%)		0/8 (0%)
Metabolism and nutrition disorders
Dehydration	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		1/6 (16.7%)		0/17 (0%)		0/8 (0%)
Musculoskeletal and connective tissue disorders
Pain in extremity	0/3 (0%)		0/8 (0%)		1/6 (16.7%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Arthralgia	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Nervous system disorders
Cerebrovascular accident	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Somnolence	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Psychiatric disorders
Mental status changes	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Renal and urinary disorders
Renal failure acute	1/3 (33.3%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/17 (5.9%)		0/8 (0%)
Calculus urinary	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Haematuria	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/3 (33.3%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Hypoxia	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Dyspnoea	0/3 (0%)		0/8 (0%)		1/6 (16.7%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Epistaxis	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		1/17 (5.9%)		0/8 (0%)
Pleural effusion	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Pulmonary oedema	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Vascular disorders
Haemorrhage	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		1/4 (25%)		0/6 (0%)		0/17 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Quizartinib 12 mg ID		Quizartinib 18 mg ID		Quizartinib 27 mg ID		Quizartinib 40 mg ID		Quizartinib 60 mg ID		Quizartinib 90 mg ID		Quizartinib 135 mg ID		Quizartinib 200 mg ID		Quizartinib 300 mg ID		Quizartinib 450 mg ID		Quizartinib 200 mg CD		Quizartinib 300 mg CD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		8/8 (100%)		5/6 (83.3%)		5/5 (100%)		5/5 (100%)		3/3 (100%)		5/5 (100%)		6/6 (100%)		4/4 (100%)		6/6 (100%)		15/17 (88.2%)		8/8 (100%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)		1/8 (12.5%)		2/6 (33.3%)		2/5 (40%)		3/5 (60%)		0/3 (0%)		1/5 (20%)		2/6 (33.3%)		2/4 (50%)		2/6 (33.3%)		5/17 (29.4%)		3/8 (37.5%)
Febrile neutropenia	0/3 (0%)		1/8 (12.5%)		1/6 (16.7%)		2/5 (40%)		1/5 (20%)		3/3 (100%)		3/5 (60%)		2/6 (33.3%)		0/4 (0%)		1/6 (16.7%)		1/17 (5.9%)		3/8 (37.5%)
Thrombocytopenia	0/3 (0%)		1/8 (12.5%)		1/6 (16.7%)		1/5 (20%)		2/5 (40%)		0/3 (0%)		1/5 (20%)		1/6 (16.7%)		1/4 (25%)		2/6 (33.3%)		2/17 (11.8%)		1/8 (12.5%)
Leukopenia	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		1/5 (20%)		0/3 (0%)		1/5 (20%)		1/6 (16.7%)		0/4 (0%)		0/6 (0%)		5/17 (29.4%)		0/8 (0%)
Neutropenia	1/3 (33.3%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		1/5 (20%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		5/17 (29.4%)		1/8 (12.5%)
Cardiac disorders
Tachycardia	0/3 (0%)		0/8 (0%)		0/6 (0%)		1/5 (20%)		1/5 (20%)		0/3 (0%)		1/5 (20%)		1/6 (16.7%)		1/4 (25%)		1/6 (16.7%)		2/17 (11.8%)		1/8 (12.5%)
Gastrointestinal disorders
Nausea	1/3 (33.3%)		2/8 (25%)		3/6 (50%)		1/5 (20%)		3/5 (60%)		2/3 (66.7%)		2/5 (40%)		5/6 (83.3%)		1/4 (25%)		4/6 (66.7%)		6/17 (35.3%)		2/8 (25%)
Diarrhoea	1/3 (33.3%)		3/8 (37.5%)		1/6 (16.7%)		0/5 (0%)		2/5 (40%)		1/3 (33.3%)		1/5 (20%)		3/6 (50%)		1/4 (25%)		4/6 (66.7%)		4/17 (23.5%)		3/8 (37.5%)
Vomiting	1/3 (33.3%)		1/8 (12.5%)		1/6 (16.7%)		1/5 (20%)		0/5 (0%)		2/3 (66.7%)		2/5 (40%)		2/6 (33.3%)		0/4 (0%)		3/6 (50%)		7/17 (41.2%)		2/8 (25%)
Abdominal pain	2/3 (66.7%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		0/5 (0%)		1/3 (33.3%)		1/5 (20%)		1/6 (16.7%)		1/4 (25%)		2/6 (33.3%)		3/17 (17.6%)		0/8 (0%)
Abdominal pain upper	0/3 (0%)		0/8 (0%)		0/6 (0%)		1/5 (20%)		0/5 (0%)		0/3 (0%)		1/5 (20%)		2/6 (33.3%)		0/4 (0%)		0/6 (0%)		4/17 (23.5%)		1/8 (12.5%)
Gingival bleeding	0/3 (0%)		1/8 (12.5%)		1/6 (16.7%)		0/5 (0%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		1/6 (16.7%)		1/4 (25%)		1/6 (16.7%)		2/17 (11.8%)		1/8 (12.5%)
General disorders
Pyrexia	0/3 (0%)		3/8 (37.5%)		1/6 (16.7%)		3/5 (60%)		2/5 (40%)		1/3 (33.3%)		1/5 (20%)		3/6 (50%)		2/4 (50%)		1/6 (16.7%)		7/17 (41.2%)		3/8 (37.5%)
Fatigue	0/3 (0%)		0/8 (0%)		2/6 (33.3%)		2/5 (40%)		2/5 (40%)		1/3 (33.3%)		3/5 (60%)		3/6 (50%)		2/4 (50%)		3/6 (50%)		6/17 (35.3%)		2/8 (25%)
Disease progression	0/3 (0%)		2/8 (25%)		0/6 (0%)		1/5 (20%)		4/5 (80%)		1/3 (33.3%)		1/5 (20%)		2/6 (33.3%)		1/4 (25%)		4/6 (66.7%)		5/17 (29.4%)		3/8 (37.5%)
Odema peripheral	1/3 (33.3%)		1/8 (12.5%)		2/6 (33.3%)		1/5 (20%)		2/5 (40%)		2/3 (66.7%)		2/5 (40%)		3/6 (50%)		2/4 (50%)		1/6 (16.7%)		3/17 (17.6%)		2/8 (25%)
Asthenia	1/3 (33.3%)		1/8 (12.5%)		0/6 (0%)		0/5 (0%)		2/5 (40%)		1/3 (33.3%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		4/6 (66.7%)		0/17 (0%)		0/8 (0%)
Chills	0/3 (0%)		1/8 (12.5%)		0/6 (0%)		1/5 (20%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)		3/6 (50%)		1/4 (25%)		1/6 (16.7%)		0/17 (0%)		0/8 (0%)
Infections and infestations
Pneumonia	0/3 (0%)		0/8 (0%)		1/6 (16.7%)		1/5 (20%)		0/5 (0%)		0/3 (0%)		0/5 (0%)		3/6 (50%)		0/4 (0%)		2/6 (33.3%)		2/17 (11.8%)		3/8 (37.5%)
Investigations
ECG QT prolonged	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		1/5 (20%)		0/3 (0%)		0/5 (0%)		0/6 (0%)		0/4 (0%)		0/6 (0%)		4/17 (23.5%)		4/8 (50%)
Metabolism and nutrition disorders
Hypokalaemia	0/3 (0%)		3/8 (37.5%)		1/6 (16.7%)		1/5 (20%)		1/5 (20%)		1/3 (33.3%)		0/5 (0%)		2/6 (33.3%)		0/4 (0%)		1/6 (16.7%)		4/17 (23.5%)		2/8 (25%)
Hypocalcaemia	0/3 (0%)		0/8 (0%)		0/6 (0%)		0/5 (0%)		1/5 (20%)		1/3 (33.3%)		1/5 (20%)		2/6 (33.3%)		0/4 (0%)		0/6 (0%)		4/17 (23.5%)		1/8 (12.5%)
Anorexia	0/3 (0%)		1/8 (12.5%)		1/6 (16.7%)		0/5 (0%)		2/5 (40%)		1/3 (33.3%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		2/6 (33.3%)		1/17 (5.9%)		0/8 (0%)
Nervous system disorders
Headache	0/3 (0%)		0/8 (0%)		2/6 (33.3%)		0/5 (0%)		2/5 (40%)		2/3 (66.7%)		1/5 (20%)		2/6 (33.3%)		0/4 (0%)		0/6 (0%)		4/17 (23.5%)		1/8 (12.5%)
Dizziness	0/3 (0%)		3/8 (37.5%)		0/6 (0%)		1/5 (20%)		1/5 (20%)		0/3 (0%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		1/6 (16.7%)		1/17 (5.9%)		2/8 (25%)
Dysgeusia	0/3 (0%)		1/8 (12.5%)		0/6 (0%)		0/5 (0%)		2/5 (40%)		1/3 (33.3%)		0/5 (0%)		1/6 (16.7%)		1/4 (25%)		0/6 (0%)		2/17 (11.8%)		2/8 (25%)
Psychiatric disorders
Confusional state	1/3 (33.3%)		1/8 (12.5%)		0/6 (0%)		1/5 (20%)		1/5 (20%)		1/3 (33.3%)		0/5 (0%)		1/6 (16.7%)		1/4 (25%)		0/6 (0%)		1/17 (5.9%)		2/8 (25%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/3 (0%)		1/8 (12.5%)		1/6 (16.7%)		1/5 (20%)		1/5 (20%)		1/3 (33.3%)		0/5 (0%)		1/6 (16.7%)		0/4 (0%)		1/6 (16.7%)		6/17 (35.3%)		2/8 (25%)
Cough	2/3 (66.7%)		2/8 (25%)		0/6 (0%)		2/5 (40%)		0/5 (0%)		1/3 (33.3%)		1/5 (20%)		2/6 (33.3%)		0/4 (0%)		0/6 (0%)		1/17 (5.9%)		3/8 (37.5%)
Dyspnoea	0/3 (0%)		2/8 (25%)		1/6 (16.7%)		1/5 (20%)		1/5 (20%)		0/3 (0%)		1/5 (20%)		2/6 (33.3%)		2/4 (50%)		0/6 (0%)		2/17 (11.8%)		1/8 (12.5%)
Skin and subcutaneous tissue disorders
Petechiae	1/3 (33.3%)		1/8 (12.5%)		2/6 (33.3%)		1/5 (20%)		0/5 (0%)		1/3 (33.3%)		0/5 (0%)		2/6 (33.3%)		1/4 (25%)		4/6 (66.7%)		3/17 (17.6%)		1/8 (12.5%)
Vascular disorders
Hypotension	1/3 (33.3%)		1/8 (12.5%)		0/6 (0%)		1/5 (20%)		1/5 (20%)		1/3 (33.3%)		0/5 (0%)		1/6 (16.7%)		1/4 (25%)		2/6 (33.3%)		1/17 (5.9%)		3/8 (37.5%)

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.