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

Venetoclax-Azacitidine in Combination With Chidamide and CAG Versus Daunorubicin and Cytarabine in Fit Older Patients With Acute Myeloid Leukaemia：A Multicenter, Randomized, Controlled, Phase 3 Trial

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 Overview

• Status: Recruiting
• Conditions: Elderly Patients; Newly Diagnosed Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: Azacytidine; Cytarabine; Aclacinomycin; Chidamide; Venetoclax; Granulocyte; Drug: the standard "3+7" regimen

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liping Dou, Doctor; Phone Number: +8613681207138; Email: lipingruirui@163.com
• Study Contact Backup: Name: Dahong Liu Liu, doctor; Phone Number: +8613681171597; Email: daihongrmg@163.com

Study Locations

• China
  • None Selected
    • Beijing, None Selected, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Liping Dou; Phone Number: +8613681207138; Email: lipingruirui@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venetoclax Combined With CACAG Regimen; The entire treatment period for the CACAG+Venetoclax regimen in the trial is 2 week, with a treatment cycle of every 4 weeks, and a total of 2 course of treatment. Chidamide: 30 mg, twice a week, for a total of 4 administrations; Azacitidine: 75 mg/m^2 from day 1 to day 7; Cytarabine (Ara-C): 75-100 mg/m^2 every 12 hours from day 1 to day 7; Aclarubicin: 20 mg/m^2 on days 1, 3, and 5; Recombinant human granulocyte colony-stimulating factor (G-CSF): 300 μg/day, to be discontinued when neutrophils recover and white blood cell count is ≥20,000/μL; Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg from day 3 to day 14, used in combination with azoles, with a reduced dosage of 100 mg/day.	Drug: Azacytidine; Cytarabine; Aclacinomycin; Chidamide; Venetoclax; Granulocyte; 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.
Active Comparator: the standard "3+7" regimen; 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.	Drug: the standard "3+7" regimen; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	1 months after study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 months after the start of study treatment
Event-free survival	Defined as the time interval from treatment initiation to the occurrence of induction failure,relapse,or death,whichever came first.	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.	From the first dose of study treatment to 30 days after the discontinuation of treatment
Early death	Defined as death within 30 days of chemotherapy.	Within 30 days of the start of the first course of treatment
Overall Survival	Defined as the time from joining the clinical study to death due to any cause.	180 days after 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.	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)	after each courses of chemotherapy (each course is 28 days)
Disease-free survival	Defined as the time interval from disease remission to the occurrence of relapse or death,whichever came first.	180 days after study treatment Outcome Measure
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).	after 1 courses of chemotherapy (each course is 28 days

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Collaborators: The General Hospital of Western Theater Command; First Affiliated Hospital of Harbin Medical University; The 960th Hospital of the PLA Joint Logistics Support Force; 940 Hospital of the People's Liberation Army Joint Logistic Support Force
• Investigators: Study Chair: Dahong Liu, Doctor, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 21, 2025
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; newly diagnosed; Elderly Patients
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Arabinonucleosides; Cytarabine; Azacitidine; venetoclax; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; aclacinomycins
• Other Study ID Numbers: KY-2024-9-140-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No