Clinical Trials List
Protocol NumberAC220-A-U302
NCT Number(ClinicalTrials.gov Identfier)NCT02668653
2016-08-01 - 2021-01-10
Phase III
Recruiting3
Terminated3
ICD-10C92.A0
Acute myeloid leukemia with multilineage dysplasia, not having achieved remission
ICD-10C92
Myeloid leukemia
A Phase 3, Double-Blind, Placebo-controlled Study of Quizartinib (AC220) Administered in Combination with Induction and Consolidation Chemotherapy, and Administered as Maintenance Therapy in Subjects 18 to 75 Years Old with Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (QuANTUM-First)
-
Trial Applicant
COVANCE TAIWAN SERVICES LIMITED
-
Sponsor
Daiichi Sankyo, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Ming-Hung Tsai 未分科
- Che-Hung Lin 未分科
- Tzu-Ting Chen 未分科
- Ming-Yu Lien 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Wei-Pang Chung 未分科
- 劉奕廷 未分科
- Shang-Yin Wu 未分科
- Ya-Ting Hsu 未分科
- Yu-Min Yeh 未分科
- Ya-Ping Chen 未分科
- Sin-Syue Li 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- Liang-Tsai Hsiao 未分科
- Hao-Yuan Wang 未分科
- Jyh-Pyng Gau 無
- Chia-Jen Liu 未分科
The Actual Total Number of Participants Enrolled
2 Recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Completed
Condition/Disease
Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia
Objectives
Primary Objective:
The primary objective is to compare the effect of quizartinib vs placebo (administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 12 cycles) on event-free survival (EFS) in subjects with newly
diagnosed FLT3-ITD (+) AML.
Test Drug
Quizartinib (AC220)
Active Ingredient
quizartinib dihydrochloride
Dosage Form
tablet
Dosage
20 , 30
Endpoints
Efficacy
The primary efficacy endpoint is EFS in the Intent-totreat (ITT) Analysis Set. Event-free survival is defined
as the time from randomization until the date of the
earliest of any of the following:
Refractory disease (or treatment failure) which
is determined at the end of the Induction Phase;
Relapse after CR, CRp or CRi;
Death from any cause at any time during the
study.
Key secondary efficacy endpoints include:
Overall survival, defined as the time from
randomization until death from any cause;
Complete remission rate which is the percent of
subjects achieving CR after Induction;
Composite complete remission rate, which is the
percent of subjects achieving CRc after
Induction;
Percent of subjects achieving CR with no
evidence of MRD following induction therapy.
Minimal residual disease is defined as the
presence of leukemic cells in the bone marrow
detected above a predefined cutoff level by a
validated assay in subjects who meet the
standard requirements for a CR.
Pharmacokinetics
PK concentration for quizartinib and its
metabolite (AC886) and PopPK analysis results.
For PK-ECG-Biomarker Substudy: PK
concentrations and PK parameters (area under
the concentration versus time curve [ng•h/mL]
from the time 0 to 24 hours [AUC0-24],
maximum plasma concentration [Cmax],
minimum plasma concentration [Cmin], and time
to maximum plasma concentration [Tmax]) for
quizartinib and AC886;
Pharmacodynamic
FLT3-ITD and FLT3-wild-type
autophosphorylation activity in an ex vivo
plasma inhibitory assay (PIA).
Biomarker
MRD (results will not be available until the end
of the study).
Mutations in the kinase and juxtamembrane
domains of FLT3-ITD and other mutations
known to be associated with AML, determined
with bone marrow or whole blood samples.
The primary efficacy endpoint is EFS in the Intent-totreat (ITT) Analysis Set. Event-free survival is defined
as the time from randomization until the date of the
earliest of any of the following:
Refractory disease (or treatment failure) which
is determined at the end of the Induction Phase;
Relapse after CR, CRp or CRi;
Death from any cause at any time during the
study.
Key secondary efficacy endpoints include:
Overall survival, defined as the time from
randomization until death from any cause;
Complete remission rate which is the percent of
subjects achieving CR after Induction;
Composite complete remission rate, which is the
percent of subjects achieving CRc after
Induction;
Percent of subjects achieving CR with no
evidence of MRD following induction therapy.
Minimal residual disease is defined as the
presence of leukemic cells in the bone marrow
detected above a predefined cutoff level by a
validated assay in subjects who meet the
standard requirements for a CR.
Pharmacokinetics
PK concentration for quizartinib and its
metabolite (AC886) and PopPK analysis results.
For PK-ECG-Biomarker Substudy: PK
concentrations and PK parameters (area under
the concentration versus time curve [ng•h/mL]
from the time 0 to 24 hours [AUC0-24],
maximum plasma concentration [Cmax],
minimum plasma concentration [Cmin], and time
to maximum plasma concentration [Tmax]) for
quizartinib and AC886;
Pharmacodynamic
FLT3-ITD and FLT3-wild-type
autophosphorylation activity in an ex vivo
plasma inhibitory assay (PIA).
Biomarker
MRD (results will not be available until the end
of the study).
Mutations in the kinase and juxtamembrane
domains of FLT3-ITD and other mutations
known to be associated with AML, determined
with bone marrow or whole blood samples.
Inclution Criteria
Inclusion Criteria:
Subjects must satisfy all of the following criteria to be
randomized:
1. Must be competent and able to comprehend, sign,
and date an Ethics Committee or Institutional
Review Board approved Informed Consent Form
(ICF) before performance of any study-specific
procedures or tests;
2. ≥18 years or the minimum legal adult age
(whichever is greater) and ≤75 years (at
Screening);
3. Newly diagnosed, morphologically documented
primary AML or AML secondary to
myelodysplastic syndrome, based on the World
Health Organization (WHO) 2008 classification (at
Screening);
4. Eastern Cooperative Oncology Group performance
status 0-2 (at Screening);
5. Presence of FLT3-ITD activating mutation in bone
marrow (allelic ratio of ≥3% FLT3-ITD/total
FLT3);
6. Subject is receiving standard "7+3" induction
chemotherapy regimen as specified in the protocol;
7. Adequate renal function defined as:
a. Serum creatinine ≤1.5 × the upper limit of
normal (ULN); or
b. Glomerular filtration rate >50 mL/min/1.73m2
,
as calculated with the modified Cockcroft Gault
equation;
8. Adequate hepatic function defined as:
a. Total serum bilirubin ≤1.5 × ULN;
b. Serum alkaline phosphatase, aspartate
transaminase and alanine transaminase ≤2.5 ×
ULN;
9. Serum electrolytes (potassium, calcium, and
magnesium) within normal limits. If outside of
normal limits, subject will be eligible when
electrolytes are corrected;
10. If female, must be either postmenopausal (no
menstrual period for a minimum of 12 months),
surgically sterile, or if of childbearing potential,
must have a negative serum pregnancy test upon
entry into this study and must be willing to use
maximally effective double-barrier birth control
during the period of therapy and contraception for
3 months following the last investigational drug
dose;
11. If male, must be surgically sterile or willing to use
an effective double-barrier contraception method
upon enrollment, during the course of the study,
and for 3 months following the last investigational
drug dose;
Subjects must satisfy all of the following criteria to be
randomized:
1. Must be competent and able to comprehend, sign,
and date an Ethics Committee or Institutional
Review Board approved Informed Consent Form
(ICF) before performance of any study-specific
procedures or tests;
2. ≥18 years or the minimum legal adult age
(whichever is greater) and ≤75 years (at
Screening);
3. Newly diagnosed, morphologically documented
primary AML or AML secondary to
myelodysplastic syndrome, based on the World
Health Organization (WHO) 2008 classification (at
Screening);
4. Eastern Cooperative Oncology Group performance
status 0-2 (at Screening);
5. Presence of FLT3-ITD activating mutation in bone
marrow (allelic ratio of ≥3% FLT3-ITD/total
FLT3);
6. Subject is receiving standard "7+3" induction
chemotherapy regimen as specified in the protocol;
7. Adequate renal function defined as:
a. Serum creatinine ≤1.5 × the upper limit of
normal (ULN); or
b. Glomerular filtration rate >50 mL/min/1.73m2
,
as calculated with the modified Cockcroft Gault
equation;
8. Adequate hepatic function defined as:
a. Total serum bilirubin ≤1.5 × ULN;
b. Serum alkaline phosphatase, aspartate
transaminase and alanine transaminase ≤2.5 ×
ULN;
9. Serum electrolytes (potassium, calcium, and
magnesium) within normal limits. If outside of
normal limits, subject will be eligible when
electrolytes are corrected;
10. If female, must be either postmenopausal (no
menstrual period for a minimum of 12 months),
surgically sterile, or if of childbearing potential,
must have a negative serum pregnancy test upon
entry into this study and must be willing to use
maximally effective double-barrier birth control
during the period of therapy and contraception for
3 months following the last investigational drug
dose;
11. If male, must be surgically sterile or willing to use
an effective double-barrier contraception method
upon enrollment, during the course of the study,
and for 3 months following the last investigational
drug dose;
Exclusion Criteria
Exclusion Criteria:
Subjects who meet any of the following criteria are not
eligible to be randomized:
1. Diagnosis of acute promyelocytic leukemia (APL),
French-American-British classification M3 or WHO
classification of APL with translocation,
t(15;17)(q22;q12), or BCR-ABL positive leukemia
(ie, chronic myelogenous leukemia in blast crisis);
2. Diagnosis of AML secondary to prior chemotherapy
or radiotherapy for other neoplasms;
3. Prior treatment for AML, except for the following
allowances:
a. Leukapheresis;
b. Treatment for hyperleukocytosis with
hydroxyurea;
c. Cranial radiotherapy for central nervous system
(CNS) leukostasis;
d. Prophylactic intrathecal chemotherapy;
e. Growth factor/cytokine support;
4. Prior treatment with quizartinib or other FLT3-ITD
inhibitors;
5. Prior treatment with any investigational drug or
device within 30 days prior to Randomization or
who are currently participating in other
investigational procedures;
6. History of known CNS leukemia, including
cerebrospinal fluid positive for AML blasts;
lumbar puncture is recommended for subjects with
symptoms of CNS leukemia to rule out
extramedullary CNS involvement;
7. History of other malignancies, except adequately
treated non-melanoma skin cancer, curatively
treated in-situ disease, or other solid tumors
curatively treated with no evidence of disease for
at least 2 years;
8. Uncontrolled or significant cardiovascular disease,
including any of the following:
a. Bradycardia of less than 50 beats per minute,
unless the subject has a pacemaker;
b. QTcF interval >450 msec;
c. Diagnosis of or suspicion of long QT syndrome
(including family history of long QT
syndrome);
d. Systolic blood pressure ≥180 mmHg or
diastolic blood pressure ≥110 mmHg;
e. History of clinically relevant ventricular
arrhythmias (eg, ventricular tachycardia,
ventricular fibrillation, or Torsade de Pointes);
f. History of second (Mobitz II) or third degree
heart block (subjects with pacemakers are
eligible if they have no history of fainting or
clinically relevant arrhythmias while using the
pacemaker);
g. History of uncontrolled angina pectoris or
myocardial infarction within 6 months prior to
Screening;
h. History of New York Heart Association Class
3 or 4 heart failure;
i. Known history of left ventricular ejection
fraction (LVEF) ≤45% or less than the
institutional lower limit of normal;
j. History of complete left or complete right
bundle branch block;
9. Active acute or chronic systemic fungal, bacterial,
or viral infection not well controlled by antifungal,
antibacterial or antiviral therapy;
10. Known active clinically relevant liver disease (eg,
active hepatitis B, or active hepatitis C)
11. Known history of human immunodeficiency virus
(HIV). Subjects should be tested for HIV prior to
randomization if required by local regulations or
EC;
12. History of hypersensitivity to any excipients in the
quizartinib/placebo tablets;
13. Females who are pregnant or breastfeeding;
14. Otherwise considered inappropriate for the study
by the investigator.
Subjects who meet any of the following criteria are not
eligible to be randomized:
1. Diagnosis of acute promyelocytic leukemia (APL),
French-American-British classification M3 or WHO
classification of APL with translocation,
t(15;17)(q22;q12), or BCR-ABL positive leukemia
(ie, chronic myelogenous leukemia in blast crisis);
2. Diagnosis of AML secondary to prior chemotherapy
or radiotherapy for other neoplasms;
3. Prior treatment for AML, except for the following
allowances:
a. Leukapheresis;
b. Treatment for hyperleukocytosis with
hydroxyurea;
c. Cranial radiotherapy for central nervous system
(CNS) leukostasis;
d. Prophylactic intrathecal chemotherapy;
e. Growth factor/cytokine support;
4. Prior treatment with quizartinib or other FLT3-ITD
inhibitors;
5. Prior treatment with any investigational drug or
device within 30 days prior to Randomization or
who are currently participating in other
investigational procedures;
6. History of known CNS leukemia, including
cerebrospinal fluid positive for AML blasts;
lumbar puncture is recommended for subjects with
symptoms of CNS leukemia to rule out
extramedullary CNS involvement;
7. History of other malignancies, except adequately
treated non-melanoma skin cancer, curatively
treated in-situ disease, or other solid tumors
curatively treated with no evidence of disease for
at least 2 years;
8. Uncontrolled or significant cardiovascular disease,
including any of the following:
a. Bradycardia of less than 50 beats per minute,
unless the subject has a pacemaker;
b. QTcF interval >450 msec;
c. Diagnosis of or suspicion of long QT syndrome
(including family history of long QT
syndrome);
d. Systolic blood pressure ≥180 mmHg or
diastolic blood pressure ≥110 mmHg;
e. History of clinically relevant ventricular
arrhythmias (eg, ventricular tachycardia,
ventricular fibrillation, or Torsade de Pointes);
f. History of second (Mobitz II) or third degree
heart block (subjects with pacemakers are
eligible if they have no history of fainting or
clinically relevant arrhythmias while using the
pacemaker);
g. History of uncontrolled angina pectoris or
myocardial infarction within 6 months prior to
Screening;
h. History of New York Heart Association Class
3 or 4 heart failure;
i. Known history of left ventricular ejection
fraction (LVEF) ≤45% or less than the
institutional lower limit of normal;
j. History of complete left or complete right
bundle branch block;
9. Active acute or chronic systemic fungal, bacterial,
or viral infection not well controlled by antifungal,
antibacterial or antiviral therapy;
10. Known active clinically relevant liver disease (eg,
active hepatitis B, or active hepatitis C)
11. Known history of human immunodeficiency virus
(HIV). Subjects should be tested for HIV prior to
randomization if required by local regulations or
EC;
12. History of hypersensitivity to any excipients in the
quizartinib/placebo tablets;
13. Females who are pregnant or breastfeeding;
14. Otherwise considered inappropriate for the study
by the investigator.
The Estimated Number of Participants
-
Taiwan
29 participants
-
Global
539 participants
