acute myeloid leukemia
Conditions
Interventions
newly diagnosed acute myeloid leukemia with FLT3 mutation:The combination therapy of Gilteritinib, Venetoclax, and Azacitidine
Sponsors
Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 90 Years
Inclusion criteria
Inclusion criteria: 1) Before undergoing any screening or research-specific procedures, the subject or their legally authorized representative (if permitted by local regulations) must voluntarily sign and date an informed consent form approved by an Independent Ethics Committee (IEC) / Institutional Review Board (IRB); 2) Definite diagnosis of AML based on the World Health Organization (WHO) classification of 2022 (during the screening period); 3) Detection of FMS-like tyrosine kinase 3 (FLT3) mutations in bone marrow or peripheral blood cells, including FLT3 internal tandem duplication (FLT3-ITD) and point mutations in the tyrosine kinase domain (FLT3-TKD); 4) Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 18 years old at the time of informed consent; 6) If a fertile female, she must have a negative serum pregnancy test result upon entering the study and must be willing to use highly effective contraceptive measures from the time of enrollment, during treatment, and for 6 months after the last dose of the study drug. Unless permanently infertile (having undergone hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), women from menarche until the start of menopause (at least 12 months of amenorrhea) are considered fertile; 7) If male, he must have undergone sterilization surgery or be willing to use highly effective contraceptive measures from the time of enrollment, during treatment, and for 6 months after the last dose of the study drug.
Exclusion criteria
Exclusion criteria: 1) Diagnosed with acute promyelocytic leukemia (APL), FAB classification M3 or PML-RARA fusion gene-positive APL under the WHO classification, as well as variant APL, BCR-ABL positive leukemia, or chronic myelogenous leukemia in blast crisis; 2) A history of CNS leukemia, including cerebrospinal fluid AML blasts positive; subjects with symptoms of CNS leukemia need to undergo lumbar puncture to 3)exclude extramedullary lesions involving the central nervous system; 3) Extramedullary involvement other than the central nervous system; 4) The following are the allowed prior treatments for AML: a. Leukapheresis; b. Use of hydroxyurea for hyperleukocytosis; c. Preventive intrathecal chemotherapy; d. Growth factor/cytokine support therapy; 5) Prior treatment with venetoclax or azacitidine; 6) Prior treatment with other FLT3 inhibitors; 7) Received any new drug or device treatment (investigational or approved immunotherapy within 2 weeks) in the 30 days before randomization or are still participating in other research treatments; 8) A history of other malignant tumors, except for adequately treated non-melanoma skin cancer, cured in situ disease, or other solid tumors cured with no signs of disease for at least 2 years; 9) Uncontrolled or significant cardiovascular disease, including any of the following: a. Bradycardia with a heart rate below 50 beats per minute, except for subjects using a pacemaker; b. QTc interval > 450ms; c. Diagnosed or suspected long QT syndrome (including a family history of long QT syndrome); d. A history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes); e. A history of second-degree (Mobitz II) or third-degree heart block (subjects using a pacemaker are eligible if they have no history of syncope or clinically significant arrhythmias while using the pacemaker); f. A history of uncontrolled angina pectoris or myocardial infarction within 6 months before screening; g. A history of heart failure classified as New York Heart Association Class 3 or 4; h. A history of left ventricular ejection fraction (LVEF) = 45% or less than the lower limit of normal; i. Complete left bundle branch block; 10) Known human immunodeficiency virus (HIV) infection; 11) Known allergy to any drug or other component in the protocol; 12) Pregnant women and women planning a pregnancy should not participate in this study; 13) According to the knowledge of the subject and the investigator, the subject may be unable to complete all the required research visits or procedures in the study protocol, including follow-up visits, and/or may be unable to comply with all required research procedures; 14) Other aspects that the investigator deems unsuitable for enrollment in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| the overall response rate (ORR) at the end of induction therapy; the complete remission rate (CR) at the end of induction therapy; | — |
Secondary
| Measure | Time frame |
|---|---|
| adverse events (CTCAE 5.0) during induction therapy, including hematological and non-hematological adverse reactions.; 2-year progression-free survival (PFS) rate;2-year overall survival (OS) rate; | — |
Countries
China
Contacts
Public ContactZhu Yu
The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital
Outcome results
None listed