Venetoclax-Azacitidine in Combination With Chidamide and CAG in Fit Older Patients With Acute Myeloid Leukaemia

Phase 2RecruitingNCT07514936

Chinese PLA General Hospital120 enrolled

Overview

This study is a multicenter, prospective, randomized, controlled clinical trial, observing the efficacy and safety of the CACAG+Venetoclax regimen (Chidamide + Azacitidine + Aclarubicin + Cytarabine + Recombinant Human Granulocyte Colony-Stimulating Factor + Venetoclax) in elderly patients with newly diagnosed Acute Myeloid Leukemia (AML). The control group applies the standard "3+7" regimen. The aim is to improve the remission rate of AML patients, reduce the probability of adverse events, and thereby improve patient prognosis and extend patient survival.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

120

Conditions

Newly Diagnosed Acute Myeloid Leukemia (AML)Elderly Patients

Interventions

IA Regimen: Idarubicin: 8-12 mg/m\^2 on days 1 to 3; Cytarabine (Ara-C): 100 mg/m\^2 every 12 hours on days 1 to 7. Or DA Regimen: Daunorubicin: 60 mg/m\^2 on days 1 to 3; Cytarabine (Ara-C): 100 mg/m\^2 every 12 hours on days 1 to 7. Or MA Regimen: Mitoxantrone: 6-10 mg/m\^2 on days 1 to 3; Cytarabine (Ara-C): 100 mg/m\^2 every 12 hours on days 1 to 7.

Azacytidine; Cytarabine; Aclacinomycin; Chidamide; Venetoclax; GranulocyteDRUG

Eligibility

Sex: ALLMin age: 60 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Voluntary participation in the clinical study; the subject or legal guardian fully understands and is informed about the study and has signed the Informed Consent Form (ICF); willing to follow and able to complete all trial procedures; 2. Age between 60-75 years at the time of screening, with no gender restrictions; 3. Patients are newly diagnosed with AML, and the diagnosis conforms to the standards of the Chinese Medical Association 2021 edition; 4. No severe allergic constitution; 5. Liver function: ALT and AST \<= 2.5 times the upper limit of normal values, bilirubin \<= 2 times the upper limit of normal values; 6. Renal function: creatinine \<= upper limit of normal values; 7. No uncontrollable infections or severe mental illnesses; 8. Performance status score is 0-3 (ECOG), with an expected survival of at least 4 months. Exclusion Criteria: 1. Patients who are allergic to the study medication or have contraindications to it; 2. Pregnant or breastfeeding women; 3. Patients with active infections; 4. Patients with long-term smoking or alcohol abuse that could affect the evaluation of trial results; 5. Patients with mental disorders or other conditions that prevent obtaining informed consent, or who are unable to cooperate with the treatment and examination procedures; 6. Patients who have undergone major organ surgery within the last 6 weeks; 7. Abnormal liver function, with total bilirubin \> 1.5 times the upper limit of normal, ALT/AST \> 2.5 times the upper limit of normal, or liver-infiltrated patients with ALT/AST \> 5 times the upper limit of normal; abnormal renal function, with serum creatinine \> 1.5 times the upper limit of normal; 8. Patients whom the investigator deems unsuitable for this clinical trial (e.g., poor compliance, drug abuse, etc.).

Outcomes

Primary Outcomes

Composite Complete Remission (CRc) Rate after 1 course of treatment

a combination of complete remission (CR) and complete remission with incomplete blood count recovery (CRi)

Time frame: 1 months after study treatment

Secondary Outcomes

Overall Response Rate (ORR) after 1 course of treatment

Defined as the percentage of participants achieving a best overall response of complete response (CR), CR with incomplete blood count recovery (CRi), or partial response (PR).Biological characteristics exploratory studies were analyzed by single-cell sequencing and Atac-seq. Further, according to European LeukemiaNet risk group, we analyzed the outcomes of patients by molecular subtype as a sub-group analysis.

Time frame: 1 months after the start of study treatment

Complete Remission (CR) Rate after 1 courses of treatment

Defined in accordance with the IWG Response Criteria in AML. Bone marrow blasts\<5 percent; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \>1.0 x 10\^9/L (1000/µL); platelet count \>100 x 109/L (100,000/µL); independence of red cell transfusions.

Time frame: after 1 courses of chemotherapy (each course is 28 days)

Rate of Minimal Residual Disease (MRD)-Negative Response

Percentage of participants who achieved MRD-negative response, defined as \< 1 leukemia cell per 10,000 leukocytes as assessed by flow cytometry after each courses of chemotherapy (each course is 28 days)

Time frame: after each courses of chemotherapy (each course is 28 days)

Event-free survival

Defined as the time interval from treatment initiation to the occurrence of induction failure,relapse,or death,whichever came first.

Time frame: 180 days after study treatment

Overall Survival

Defined as the time from joining the clinical study to death due to any cause.

Time frame: 180 days after study treatment

Treatment-related adverse events

Defined as adverse events that occurred from the first dose of study treatment to 30 days after the discontinuation of treatment.

Time frame: From the first dose of study treatment to 30 days after the discontinuation of treatment

Disease-free survival

Defined as the time interval from disease remission to the occurrence of relapse or death,whichever came first.

Time frame: 180 days after study treatment Outcome Measure

Early death

Defined as death within 30 days of chemotherapy.

Time frame: Within 30 days of the start of the first course of treatment

Complete Remission with Incomplete Blood Count Recovery (CRi)after 1 courses of treatment

Disappearance of leukemia blasts in the bone marrow (\<5% blasts) but without full recovery of blood counts (neutrophils \<1.0 x 10⁹/L and/or platelets \<100 x 10⁹/L).

Time frame: after 1 courses of chemotherapy (each course is 28 days

Central Contacts

Dahong Liu Liu, doctor

CONTACT

+8613681171597 daihongrmg@163.com

Liping Dou, Doctor