The Efficacy of Triple Regimen in Newly Diagnosed AML Patients With FLT3 Mutation

Phase 1

Not yet recruiting

Brief Summary: The FMS tyrosine kinase 3 (FLT3) gene mutation occurs in 30% of newly diagnosed AML patients, leading to a higher relapse rate and mortality rate. In the past, multi-drug combination chemotherapy regimens had limited efficacy in newly diagnosed AML patients with FLT3 mutations, especially in those with FLT3-ITD. However, the FLT3 inhibitors greatly improved ...

Detailed Description: This stuay intends to conduct a multi-center, single-arm clinical study to explore the efficacy of the triple induction regimen consisting of Gilteritinib, Venetoclax, and Azacitidine in newly diagnosed FLT3 mutated AML patients who are suitable for intensive chemotherapy. The maximum dose of Gilteritinib that can be safely combined with Azacitidine and Vene...

Recruitment & Eligibility

Inclusion Criteria

MDS/AML patients WHO meet AML and ICC definitions according to WHO (2022) or ICC standards (10%-20% of bone marrow naive cells) and have FLT3-TKD or ITD mutations detected by PCR or second-generation sequencing.
Age ≥15 years old, male or female.
The physical status assessment (ECOG-PS) of the Eastern Oncology Collaboration group was 0-2 points.
Pass the requirements of the following laboratory tests (performed within 7 days before treatment) :

Total bilirubin ≤ 1.5 times the upper limit of normal value (same age); 2) AST and ALT≤ 2.5 times the upper limit of normal value (same age); 3) Blood creatinine < 2 times the upper limit of normal (same age); 4) Myocardial enzymes < 2 times the upper limit of normal (same age); 5) Echocardiography (ECHO) was performed to determine the ejection fraction of the heart within the normal range.

Exclusion Criteria

Acute promyelocytic leukemia with PML-RARA fusion gene
Acute myeloid leukemia with RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene
Acute myeloid leukemia with BCR-ABL fusion gene
Have treated patients (those who have previously received induction chemotherapy but can receive hydroxyurea down-cell therapy).
Concurrent malignant tumors of other organs (those requiring treatment).
Active heart disease, defined as one or more of the following:

A history of uncontrolled or symptomatic angina; 2) Myocardial infarction less than 6 months after enrollment; 3) Have a history of arrhythmia requiring drug treatment or severe clinical symptoms; 4) Uncontrolled or symptomatic congestive heart failure (> NYHA level 2); 5) The ejection fraction is lower than the lower limit of the normal range. 7. Serious infectious diseases (uncured tuberculosis, pulmonary aspergillosis). 8. Those who were not considered suitable for inclusion by the researchers.

Arm && Interventions

Group	Intervention	Description
Triple Regimen Induction Including Gilteritinib, Venetoclax and Azacitidine	Gilteritinib	Patients will receive 2 courses of induction with a triple regimen therapy consisting of Gilteritinib, Venetoclax, and Azacitidine. Patients who achieved complete remission will receive 3 courses of intermediate-dose cytarabine for consolidation. After consolidation therapy, dose-adjusted triple regimen therapy including Gilteritinib, Venetoclax, and Azacitidine will be applied for 6 courses as maintenance treatment.
Triple Regimen Induction Including Gilteritinib, Venetoclax and Azacitidine	Cytarabine	Patients will receive 2 courses of induction with a triple regimen therapy consisting of Gilteritinib, Venetoclax, and Azacitidine. Patients who achieved complete remission will receive 3 courses of intermediate-dose cytarabine for consolidation. After consolidation therapy, dose-adjusted triple regimen therapy including Gilteritinib, Venetoclax, and Azacitidine will be applied for 6 courses as maintenance treatment.

Primary Outcome Measures

Name	Time	Method
Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) with negative MRD detected by flow cytometry.	up to 1 years after the date of the last enrolled participants	The ratio of CR/CRh/CRi with negative MRD detected by flow cytometry after induction, consolidation, and maintenance therapy.
To determine the maximum tolerated dose of gilteritinib	up to 3 months after enrollment of the first participants	The maximum dose of gilteritinib that can be safely combined with azacitidine and venetoclax
Event-free survival (EFS)	up to 2 years after the date of the last enrolled participants	The interval from the date of enrollment to the date of failed to achieve complete remission, the date of relapse, or the date of death, whichever occurred first.
CR/CRh/CRi with negative MRD detected by NGS (next-generation sequencing)	up to 1 years after the date of the last enrolled participants	The ratio of CR/CRh/CRi with negative MRD detected by NGS after induction,consolidation, and maintenance therapy.

Secondary Outcome Measures

Name	Time	Method
overall survival	up to 2 years after the date of the last enrolled participants	The interval from the date of enrollment to the date of death or the date of last follow-up, , whichever occurred first.
60-day mortality	Within 60 days of the date of the last enrolled participants	Percentage of patients who died within 60 days from enrollment
CR/CRh/CRi rate	up to 3 months after the date of the last enrolled participants	The ratio of patients achieved CR/CRh/CRi after two course of induction therapy
Relapse free survival	up to 2 years after the date of the last enrolled participants	The interval from CR to the date of relapse, or the date of death, or the date of last follow-up, whichever occurred first. This outcome analyzes patients achieved CR in two courses of induction therapy.
30-day mortality	Within 30 days of the date of the last enrolled participants	Percentage of patients who died within 30 days from enrollment