Clinical Trials List
Protocol NumberAC220-007
NCT Number(ClinicalTrials.gov Identfier)NCT02039726
Completed
2016-01-01 - 2017-12-31
Phase III
Terminated4
ICD-10C92.A0
Acute myeloid leukemia with multilineage dysplasia, not having achieved remission
A PHASE 3 OPEN-LABEL RANDOMIZED STUDY OF QUIZARTINIB (AC220) MONOTHERAPY VERSUS SALVAGE CHEMOTHERAPY IN SUBJECTS WITH FLT3-ITD POSITIVE ACUTE MYELOID LEUKEMIA (AML) REFRACTORY TO OR RELAPSED AFTER FIRST-LINE TREATMENT WITH OR WITHOUT HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) CONSOLIDATION
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Trial Applicant
Daiichi Sankyo Taiwan Ltd.
-
Sponsor
Ambit Biosciences Corporation (A wholly owned subsidiary of Daiichi Sankyo, Inc.)
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Yu-Min Yeh Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- Sin-Syue Li Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- Ching-Chan Lin Division of Hematology & Oncology
- Tzu-Ting Chen Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
- Ming-Yu Lien Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chia-Jen Liu Division of Hematology & Oncology
- 曾成槐 Division of Hematology & Oncology
- Jin-Hwang Liu Division of Hematology & Oncology
- 余垣斌 Division of Hematology & Oncology
- Liang-Tsai Hsiao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- MING YAO Division of Hematology & Oncology
- Chien-Yuan Chen Division of Hematology & Oncology
- Sheng-chieh Chou Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- 蔡偉 Division of Hematology & Oncology
- 李啟誠 Division of Hematology & Oncology
- HSIN-AN HOU Division of Hematology & Oncology
- 陳尹愷 Division of Hematology & Oncology
- Chien-Chin Lin Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- Wen-Chien Chou Division of Hematology & Oncology
- 林建廷 Division of Hematology & Oncology
- 劉家豪 Division of Hematology & Oncology
- Tai-Chung Huang Division of Hematology & Oncology
- Jih-Luh Tang Division of Hematology & Oncology
- 徐思淳 Division of Hematology & Oncology
- Shang-Ju Wu Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Acute Myeloid Leukemia (AML)
Objectives
The primary objective of the study is to determine whether quizartinib monotherapy prolongs overall survival (OS) compared to salvage chemotherapy in subjects with FMS-like tyrosine kinase 3 - Internal Tandem Duplication (FLT3-ITD) positive AML who are refractory to or have relapsed within 6 months, after first-line AML therapy.
Test Drug
Quizartinib (AC220)
Active Ingredient
Quizartinib (AC220)
Dosage Form
film-coated tablet
Dosage
20 and 30
Endpoints
Primary Outcome Measures :
1. Overall Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy [ Time Frame: At approximately 3 years 9 months ]
Overall Survival is defined as the time (in weeks) from the date of randomization to the date of death due to any cause. Median and quartiles are calculated using the Kaplan-Meier method.
Secondary Outcome Measures :
1. Event-free Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy [ Time Frame: At approximately 3 years 9 months ]
Event-free survival is defined as the time (in weeks) from randomization until documented refractory disease, relapse after complete composite remission (CRc), or death from any cause, whichever is observed first.
1. Overall Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy [ Time Frame: At approximately 3 years 9 months ]
Overall Survival is defined as the time (in weeks) from the date of randomization to the date of death due to any cause. Median and quartiles are calculated using the Kaplan-Meier method.
Secondary Outcome Measures :
1. Event-free Survival in Participants That Received Quizartinib Versus Salvage Chemotherapy [ Time Frame: At approximately 3 years 9 months ]
Event-free survival is defined as the time (in weeks) from randomization until documented refractory disease, relapse after complete composite remission (CRc), or death from any cause, whichever is observed first.
Inclution Criteria
Inclusion Criteria
To be able to participate in this study, candidates must meet the following criteria at screening or
other specified time point:
1. Provision of written informed consent approved by the Institutional Review Board (IRB)
or Independent Ethics Committee (IEC) with privacy language in accordance with
national regulations (e.g., HIPAA authorization for US sites) prior to any study-related
procedures, including withdrawal of prohibited medications if applicable.
2. Age ≥18 years at the time of informed consent.
3. Morphologically documented primary AML or AML secondary to myelodysplastic
syndrome (MDS), as defined by World Health Organization criteria, as determined by
pathology review at the study site.
4. In first relapse (with duration of remission of 6 months or less) or refractory after prior
therapy, with or without HSCT. Induction therapy must have included at least 1 cycle of
an anthracycline/mitoxantrone-containing induction block at a standard dose.
• Refractory is defined as:
• After 1 cycle, a reduction in bone marrow blasts of less than 50% and failure to
achieve a CR, CRp or CRi.
• After 2 cycles, lack of achievement of CR, CRp, or CRi.
• First relapse (with duration of remission of 6 months or less) is defined as:
• Achievement of CR, CRi, or CRp, as defined by 2003 International Working Group
criteria (Section 7.2) after initial AML therapy with or without consolidation or
maintenance, and with or without HSCT.
• Duration of CR, CRi or CRp is measured from the date of the bone marrow
assessment which confirmed response or the date of allogeneic transplantation, to the
date of the bone marrow assessment that identified relapse or the appearance of
peripheral blasts.
5. Presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood
(allelic ratio as determined by a central laboratory with a cutoff of
≥3% FLT3-ITD/total FLT3).
6. Eligibility for pre-selected salvage chemotherapy, according to the Investigator’s
assessment.
7. ECOG performance score 0-2.
8. Discontinuation of prior AML treatment before the start of study treatment (except
hydroxyurea or other treatment to control leukocytosis) for at least 2 weeks for cytotoxic
agents, or for at least 5 half-lives for non-cytotoxic agents.
9. Serum creatinine ≤1.5×upper limit of normal (ULN), or glomerular filtration rate
>25 mL/min, as calculated with the Cockcroft-Gault formula.
10. Serum potassium, magnesium, and calcium (serum calcium corrected for
hypoalbuminemia) within institutional normal limits. Subjects with electrolytes outside
the normal range will be eligible if these values are corrected upon retesting following
any necessary supplementation.
11. Total serum bilirubin ≤1.5×ULN.
12. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5×ULN.
To be able to participate in this study, candidates must meet the following criteria at screening or
other specified time point:
1. Provision of written informed consent approved by the Institutional Review Board (IRB)
or Independent Ethics Committee (IEC) with privacy language in accordance with
national regulations (e.g., HIPAA authorization for US sites) prior to any study-related
procedures, including withdrawal of prohibited medications if applicable.
2. Age ≥18 years at the time of informed consent.
3. Morphologically documented primary AML or AML secondary to myelodysplastic
syndrome (MDS), as defined by World Health Organization criteria, as determined by
pathology review at the study site.
4. In first relapse (with duration of remission of 6 months or less) or refractory after prior
therapy, with or without HSCT. Induction therapy must have included at least 1 cycle of
an anthracycline/mitoxantrone-containing induction block at a standard dose.
• Refractory is defined as:
• After 1 cycle, a reduction in bone marrow blasts of less than 50% and failure to
achieve a CR, CRp or CRi.
• After 2 cycles, lack of achievement of CR, CRp, or CRi.
• First relapse (with duration of remission of 6 months or less) is defined as:
• Achievement of CR, CRi, or CRp, as defined by 2003 International Working Group
criteria (Section 7.2) after initial AML therapy with or without consolidation or
maintenance, and with or without HSCT.
• Duration of CR, CRi or CRp is measured from the date of the bone marrow
assessment which confirmed response or the date of allogeneic transplantation, to the
date of the bone marrow assessment that identified relapse or the appearance of
peripheral blasts.
5. Presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood
(allelic ratio as determined by a central laboratory with a cutoff of
≥3% FLT3-ITD/total FLT3).
6. Eligibility for pre-selected salvage chemotherapy, according to the Investigator’s
assessment.
7. ECOG performance score 0-2.
8. Discontinuation of prior AML treatment before the start of study treatment (except
hydroxyurea or other treatment to control leukocytosis) for at least 2 weeks for cytotoxic
agents, or for at least 5 half-lives for non-cytotoxic agents.
9. Serum creatinine ≤1.5×upper limit of normal (ULN), or glomerular filtration rate
>25 mL/min, as calculated with the Cockcroft-Gault formula.
10. Serum potassium, magnesium, and calcium (serum calcium corrected for
hypoalbuminemia) within institutional normal limits. Subjects with electrolytes outside
the normal range will be eligible if these values are corrected upon retesting following
any necessary supplementation.
11. Total serum bilirubin ≤1.5×ULN.
12. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5×ULN.
Exclusion Criteria
Exclusion Criteria
Candidates will be excluded from study entry if any of the following criteria are met at screening
or other specified time point:
1. Acute promyelocytic leukemia (AML subtype M3)
2. AML secondary to prior chemotherapy for other neoplasms, except AML secondary
to prior MDS
3. History of another malignancy, unless the candidate has been disease-free for at least
5 years
• Candidates with treated non-melanoma skin cancer, carcinoma in situ, or cervical
intraepithelial neoplasia are eligible regardless of the time spent disease-free, if
they have completed definitive treatment
• Candidates with organ-confined prostate cancer, with no evidence of recurrent or
progressive disease, are eligible if hormonal therapy has been begun, or if the
tumor has been surgically removed or treated with definitive radiotherapy
4. Persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML
therapy
5. Clinically significant GVHD or GVHD requiring initiation of treatment or treatment
escalation within 21 days, and/or > Grade 1 persistent or clinically significant
non-hematologic toxicity related to HSCT
6. History of or current, central nervous system involvement with AML
7. Clinically significant coagulation abnormality, such as disseminated intravascular
coagulation
8. Prior treatment with quizartinib or participated in a prior quizartinib study
9. Prior treatment with a FLT3 targeted therapy including sorafenib or investigational
FLT3 inhibitors
10. Major surgery within 4 weeks prior to screening
11. Radiation therapy within 4 weeks prior to screening
12. Uncontrolled or significant cardiovascular disease, including:
• QTcF interval >450 msec (average of triplicate determinations)
• Subject has bradycardia of less than 50 BPM (as determined by central reading)
unless the subject has a pacemaker
• Diagnosed or suspected long QT syndrome, or known family history of long
QT syndrome
• History of clinically relevant ventricular arrhythmias, such as ventricular
tachycardia, ventricular fibrillation, or torsade de pointes
• History of second or third degree heart block. Candidates with a history of heart
block may be eligible if they currently have pacemakers, and have no history of
fainting or clinically relevant arrhythmia with pacemakers.
• Myocardial infarction within 6 months prior to screening
• Uncontrolled angina pectoris within 6 months prior to screening
• New York Heart Association (NYHA) Class 3 or 4 congestive heart failure
• Left ventricular ejection fraction (LVEF) ≤45% or institutional lower limit of
normal
• Uncontrolled hypertension
• Complete left or right bundle branch block
13. Active infection not well controlled by antibacterial or antiviral therapy
14. Known infection with human immunodeficiency virus, or active hepatitis B or C, or
other active clinically relevant liver disease
15. Unwillingness to receive infusion of blood products according to the protocol
16. In a man whose sexual partner is a woman of childbearing potential, unwillingness or
inability of the man or woman to use an acceptable contraceptive method for the
entire study treatment period and for at least 3 months after study treatment
completion
• Male subjects must not donate sperm starting at Screening and throughout the
study period, and 105 days after the final study drug administration.
17. In a heterosexually active woman of childbearing potential, unwillingness or inability
to use an acceptable contraceptive method for the entire study treatment period and
for at least 3 months after study treatment completion. Additionally, for women
randomized to chemotherapy, unwillingness to adhere to the restrictions in the
respective Summary of Product Characteristics and the Patient Information Leaflet
(package insert) as instructed by the Investigator.
• Women are not regarded as of childbearing potential if they are post-menopausal
(at least 2 years without menses) or are surgically sterile (at least 1 month before
study).
• Acceptable contraception comprises two forms of birth control (one of which
must be a barrier method).
• Female subjects must not donate ova started at Screening and throughout the
study treatment period, and for 105 days after the final study drug administration.
18. Pregnancy
19. Female subjects must agree not to breastfeed at Screening and throughout the study
period, and for 45 days after the final study drug administration.
20. Medical condition, serious intercurrent illness, or other circumstance that, in the
Investigator’s judgment, could jeopardize the candidate’s safety as a study subject, or
that could interfere with study objectives.
Candidates will be excluded from study entry if any of the following criteria are met at screening
or other specified time point:
1. Acute promyelocytic leukemia (AML subtype M3)
2. AML secondary to prior chemotherapy for other neoplasms, except AML secondary
to prior MDS
3. History of another malignancy, unless the candidate has been disease-free for at least
5 years
• Candidates with treated non-melanoma skin cancer, carcinoma in situ, or cervical
intraepithelial neoplasia are eligible regardless of the time spent disease-free, if
they have completed definitive treatment
• Candidates with organ-confined prostate cancer, with no evidence of recurrent or
progressive disease, are eligible if hormonal therapy has been begun, or if the
tumor has been surgically removed or treated with definitive radiotherapy
4. Persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML
therapy
5. Clinically significant GVHD or GVHD requiring initiation of treatment or treatment
escalation within 21 days, and/or > Grade 1 persistent or clinically significant
non-hematologic toxicity related to HSCT
6. History of or current, central nervous system involvement with AML
7. Clinically significant coagulation abnormality, such as disseminated intravascular
coagulation
8. Prior treatment with quizartinib or participated in a prior quizartinib study
9. Prior treatment with a FLT3 targeted therapy including sorafenib or investigational
FLT3 inhibitors
10. Major surgery within 4 weeks prior to screening
11. Radiation therapy within 4 weeks prior to screening
12. Uncontrolled or significant cardiovascular disease, including:
• QTcF interval >450 msec (average of triplicate determinations)
• Subject has bradycardia of less than 50 BPM (as determined by central reading)
unless the subject has a pacemaker
• Diagnosed or suspected long QT syndrome, or known family history of long
QT syndrome
• History of clinically relevant ventricular arrhythmias, such as ventricular
tachycardia, ventricular fibrillation, or torsade de pointes
• History of second or third degree heart block. Candidates with a history of heart
block may be eligible if they currently have pacemakers, and have no history of
fainting or clinically relevant arrhythmia with pacemakers.
• Myocardial infarction within 6 months prior to screening
• Uncontrolled angina pectoris within 6 months prior to screening
• New York Heart Association (NYHA) Class 3 or 4 congestive heart failure
• Left ventricular ejection fraction (LVEF) ≤45% or institutional lower limit of
normal
• Uncontrolled hypertension
• Complete left or right bundle branch block
13. Active infection not well controlled by antibacterial or antiviral therapy
14. Known infection with human immunodeficiency virus, or active hepatitis B or C, or
other active clinically relevant liver disease
15. Unwillingness to receive infusion of blood products according to the protocol
16. In a man whose sexual partner is a woman of childbearing potential, unwillingness or
inability of the man or woman to use an acceptable contraceptive method for the
entire study treatment period and for at least 3 months after study treatment
completion
• Male subjects must not donate sperm starting at Screening and throughout the
study period, and 105 days after the final study drug administration.
17. In a heterosexually active woman of childbearing potential, unwillingness or inability
to use an acceptable contraceptive method for the entire study treatment period and
for at least 3 months after study treatment completion. Additionally, for women
randomized to chemotherapy, unwillingness to adhere to the restrictions in the
respective Summary of Product Characteristics and the Patient Information Leaflet
(package insert) as instructed by the Investigator.
• Women are not regarded as of childbearing potential if they are post-menopausal
(at least 2 years without menses) or are surgically sterile (at least 1 month before
study).
• Acceptable contraception comprises two forms of birth control (one of which
must be a barrier method).
• Female subjects must not donate ova started at Screening and throughout the
study treatment period, and for 105 days after the final study drug administration.
18. Pregnancy
19. Female subjects must agree not to breastfeed at Screening and throughout the study
period, and for 45 days after the final study drug administration.
20. Medical condition, serious intercurrent illness, or other circumstance that, in the
Investigator’s judgment, could jeopardize the candidate’s safety as a study subject, or
that could interfere with study objectives.
The Estimated Number of Participants
-
Taiwan
8 participants
-
Global
363 participants
