This study aims to investigate the safety and efficacy of drug "X" in combination with intensive chemotherapy in subjects with newly diagnosed AML (excluding APL and CBF-AML). "X" drugs included BCL-2 inhibitor venetoclax and FLT3 inhibitor Gilteritinib. Subjects will receive standard intensive chemotherapy during induction and consolidation. Early induction response will be evaluated according to the results of peripheral blood blast clearance rate on the fifth day after induction therapy (D5-PBCR). Venetoclax will be added in D5-PBCR positive subjects. For subjects with FLT3 mutations, Gilteritinib will be combined. Subjects will be stratified based on the genetic risk classification of 2022 European LeukemiaNet recommendations (ELN risk) and MRD status to receive specific consolidation therapy after the induction therapy.
Young patients with naïve AML (excluding APL and CBF-AML) were included in this study. 218 subjects who meet the eligibility criteria will receive the standard 3+7 intensive chemotherapy induction, containing cytarabine and idarubicin. On the basis of the IA induction regimen, the early chemotherapy response was evaluated according to the results of peripheral blood blast clearance rate on the fifth day after induction therapy (D5-PBCR). For D5-PBCR-positive patients, venetoclax will be added to conventional chemotherapy. For patients with FLT3 mutations, gilteritinib will be combined. Subjects who achieve a composite complete remission (CRc) after induction therapy will receive further consolidation therapy, which regimen will be decided based on the ELN risk at diagnosis and MRD status detected by MFC and gene quantification after induction therapy. The purpose of the study is to determine whether the addition of drug "X" to the standard induction regimen improves efficacy in the treatment of naïve AML. Primary objective: To evaluate whether intensive IA combined with targeted drug (drug "X") regimens can improve the composite response rate (CRc) after 1 course of induction therapy in newly diagnosed young AML patients Secondary Objective: To evaluate whether intensive chemotherapy combined with drug "X" during induction and consolidation can improve overall response rates, overall survival, and event-free survival in newly diagnosed young AML patients Safety indicators: incidence of adverse reactions during treatment, recovery time of neutrophils and platelets
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
218
Induction: IA Drug: idarubicin, intravenously, 10 mg/m\^2 on D1-3 Drug: cytarabine, intravenously, 100 mg/m\^2 on D1-7 Consolidation: Subjects who achieve composite complete remission (CRc) proceed with consolidation therapy. In consolidation therapy phase, subjects in the group with favorable/intermediate risk and MRD negetive, will receive cytarabine intravenously at 2g/m\^2/q12h\*6 doses. Subjects in the group with adverse risk or MRD positive will receive cytarabine intravenously at 2g/m\^2/q12h\*6 doses together with venetoclax 400mg on D4-10. Dose ramp-up of venetoclax is not required. After two cycles of consolidation, a multi-disciplinary team will discuss whether the patient need allogeneic hematopoietic stem-cell transplant (allo-HSCT) according to ELN risk stratification and MRD status.
Induction: IA+Ven Drug: idarubicin, intravenously, 10 mg/m\^2, on D1-3, Drug: cytarabine, intravenously, 100 mg/m\^2 on D1-7 For D5-PBCR (+) patients, Venetoclax will be combined. Drug: Venetoclax. Orally once daily, on D6-14. A 3-day dose ramp-up is required for the first induction (100mg D6, 200mg D7, 400mg D8-14) If a second induction is needed, the dose of IA is the same as the first cycle, and dose ramp-up of venetoclax is not required. Consolidation: Subjects who achieve composite complete remission (CRc) proceed with consolidation therapy. In consolidation therapy phase, subjects in the group will receive cytarabine intravenously at 2g/m\^2/q12h\*6 doses together with venetoclax 400mg on D4-10. Dose ramp-up of venetoclax is not required. After two cycles of consolidation, a multi-disciplinary team will discuss whether the patient need allogeneic hematopoietic stem-cell transplant (allo-HSCT) according to ELN risk stratification and MRD status.
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, China
Composite complete remission rate
Complete remission/complete remission with partial hematological recovery/complete remission with incomplete hematological recovery
Time frame: At the end of cycle one (up to 42 days from the start of cycle 1)
Total composite complete remission rate
Complete remission/complete remission with partial hematological recovery/complete remission with incomplete hematological recovery
Time frame: At the end of induction cycle 2 (up to 42 days from the start of cycle 2)
OS
overall survival rate
Time frame: 2-year
EFS
event free survival rate
Time frame: 2-year
AE
Adverse Events (AEs), Serious Adverse Events (SAEs) Based on NCI-CTCAE 5.0 Assessment
Time frame: Throughout the entire study period, an average of 1 year
Recovery time for neutrophils and platelets
The time from the first day of induction therapy to the recovery of neutrophils to a count greater than 0.5\*10\^9/L and platelets to greater than 20\*10\^9/L
Time frame: During induction cycle one (up to 42 days from the start of cycle 1)
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