Open-label, Single-arm Study Evaluating the Efficacy and Safety of Quizartinib in Combination with Standard Chemotherapy in Patients with NewlyDiagnosed FLT3-ITD-positive Acute Myeloid Leukemia (JALSG-AML224-FLT3-ITD)
JALSG-AML224-FLT3-ITD (JALSG-AML224-FLT3-ITD)
Ishikawa Yuichi
Nagoya University Hospital
65 Tsurumai-cho, Showa-ku, Nagoya-shi, Aichi
+81-52-741-2111
yishikaw@med.nagoya-u.ac.jp
Ishikawa Yuichi
Nagoya University Hospital
65 Tsurumai-cho, Showa-ku, Nagoya-shi, Aichi
+81-52-741-2111
yishikaw@med.nagoya-u.ac.jp
Recruiting
May. 30, 2025
150
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
1.Patients who have provided written informed consent after receiving a full explanation of this study.
2.Patients aged 18 years or older and under 65 years at the time of consent.
3.Patients with newly diagnosed AML morphologically confirmed based on the WHO classification (2017), AML secondary to myelodysplastic syndrome (MDS), or AML secondary to myeloproliferative neoplasms (MPN).
4.Patients with an ECOG performance status (PS) of 0-2.
5.Patients with an FLT3-ITD mutation detected in bone marrow or peripheral blood (patients evaluated as positive in the CDx FLT3 mutation test).
6.Patients who have initiated remission induction therapy with standard cytarabine in combination with idarubicin or daunorubicin.
7.Patients who meet all of the following criteria and are determined to have sufficient organ function before undergoing remission induction therapy with standard cytarabine in combination with idarubicin or daunorubicin:
a) Serum creatinine: <=1.5 x ULN
b) Pre-treatment PaO2 in room air >=60 Torr or SpO2 >=90%
c) Total bilirubin: <=1.5 x ULN (exceptions apply for confirmed Gilbert's syndrome or cases where an increase in total bilirubin is associated with elevated unconjugated [indirect] bilirubin due to hemolysis).
8.Male patients or female patients of childbearing potential who agree to use contraception during the study and for a specified period after the final dose of quizartinib (4 months for males, 7 months for females).
1.Patients diagnosed with acute promyelocytic leukemia (APL) (M3 according to the French-American-British [FAB] classification or APL with PML::RARA fusion according to the WHO classification) or BCR::ABL1-positive leukemia (i.e., blast crisis of chronic myeloid leukemia). Subjects who underwent diagnostic testing for APL and received treatment with all-trans retinoic acid (ATRA) but were subsequently determined not to have APL may be enrolled (treatment with ATRA must be discontinued before the initiation of remission induction therapy).
2.Patients with a history of AML treatment, except for the following:
a) Leukapheresis
b) Administration of hydroxyurea for leukocytosis
c) Cranial radiotherapy for central nervous system (CNS) leukostasis
d) Prophylactic intrathecal chemotherapy
e) Supportive administration of growth factors, hormonal agents, or cytokines
3.Patients who have received an investigational drug within 30 days prior to obtaining consent or are currently participating in another clinical trial.
4.Patients with active CNS leukemia (including those with AML blasts detected in cerebrospinal fluid testing). A lumbar puncture is recommended for patients presenting with CNS leukemia symptoms to rule out extramedullary (CNS) infiltration.
5.Patients with a history of malignant tumors, except for the following:
a) Non-melanoma skin cancer that has been adequately treated
b) In situ lesions that have undergone curative treatment
c) Other solid tumors that have undergone curative treatment and have been free of disease for at least two years
6.Patients with uncontrolled or significant cardiovascular disease, including any of the following:
a) Bradycardia with a heart rate of less than 50 bpm (except in patients using a pacemaker)
b) QTcF interval exceeding 450 ms
c) Diagnosed or suspected long QT syndrome (including a family history of long QT syndrome)
d) History of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
e) History of second-degree (Mobitz type II) or third-degree heart block (patients with a pacemaker who have no history of syncope or clinically significant arrhythmia under pacemaker use may be enrolled)
f) Left ventricular ejection fraction (LVEF) <=50% on echocardiography or below the institution's lower limit of normal
g) Uncontrolled angina or a history of myocardial infarction within six months prior to obtaining consent
7.Patients with acute or chronic systemic fungal, bacterial, or viral infections that are not adequately controlled with antifungal, antibacterial, or antiviral agents.
8.Patients diagnosed with clinically significant active liver disease, such as active hepatitis B or active hepatitis C.
9.Patients with a confirmed history of human immunodeficiency virus (HIV) infection.
10.Patients with a history of hypersensitivity to quizartinib tablets or any excipients contained in the investigational drug.
11.Pregnant or breastfeeding women.
12.Patients with uncontrolled Grade 3 or 4 hypokalemia, hypomagnesemia, or hypocalcemia (patients with Grade 1 or 2 electrolyte abnormalities may be enrolled if electrolyte levels are corrected).
13.Patients deemed unsuitable for the study by the principal investigator or sub-investigator for any other reason.
Following induction therapy with intensive chemotherapy, quizartinib is administered. In patients who achieve complete remission, up to four courses of high-dose cytarabine in combination with quizartinib are given during the consolidation phase. Furthermore, maintenance therapy with quizartinib monotherapy is administered for up to 36 courses.
1-year relapse-free survival rate in patients who achieved CR
Evaluation of Safety Profile
- Adverse events
- Cumulative incidence of GVHD
- Clinical laboratory values (hematologic tests)
- Usage status of treatment drugs (antifungal agents, G-CSF, transfusion)
Efficacy Outcomes
Complete remission (CR) rate and composite complete remission (CRc) rate at the end of induction therapy
CR rate and CRc rate at the end of consolidation therapy and before transplantation
Proportion of FLT3-ITD measurable residual disease (MRD)-negative cases at the end of consolidation therapy, before transplantation, and after transplantation
Time to achievement of CR/CRc
Duration of CR/CRc
Relapse-free survival (RFS) in patients who achieved CRc
Event-free survival (EFS)
Overall survival (OS)
Transplantation rate
Cumulative incidence of relapse (CIR) after transplantation
Cumulative incidence of non-relapse mortality (CINRM) after transplantation
DAIICHI SANKYO COMPANY, LIMITED
National Hospital Organization Review Board for Clinical Tria ls (Nagoya)
