A Multicenter RCT of "3+7" vs Venetoclax + CACAG in Newly Diagnosed Mid/High-Risk AML Patients

A Multicenter, Prospective, Randomized Controlled Study of the Standard "3+7" Regimen Versus Venetoclax Combined With CACAG Regimen in Newly Diagnosed Adult Patients With Intermediate- and High-risk Acute Myeloid Leukemia

The purpose of this study is to compare the efficacy and safety of venetoclax combined with the CACAG regimen with the traditional "3+7" regimen in the treatment of newly diagnosed intermediate- or high-risk acute myeloid leukemia (AML).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; First Line Therapy
• Intervention / Treatment: Drug: Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor; Drug: "3+7"

Detailed Description

Despite the availability of hematopoietic stem cell transplantation and the emergence of many new therapeutic drugs, the prognosis of newly diagnosed acute myeloid leukemia is still poor.Over the past years, combination chemotherapy with anthracycline and standard dose cytarabine (standard "3+7" induction therapy) remains the standard induction. In order to improve the outcome of patients with de novo AML, we developed a venetoclax combined with CACAG regimen in the treatment of de novo AML. In this study, we intent to compare the efficacy and safety of venetoclax combined with CACAG regimen with the traditional "3+7" regimen in the treatment of newly diagnosed intermediate- or high-risk acute myeloid leukemia.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Daihong Liu, doctor; Phone Number: 86-13681171597; Email: daihongrm@163.com
      • Contact: Qingyang Liu, doctor; Phone Number: +8617808071170; Email: 1074745197@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Age 14 to 75 years (no gender limitation) Newly diagnosed with intermediate- or high-risk AML (excluding M3) Liver function: ALT and AST ≤ 2.5 times upper limit of normal; bilirubin ≤ 2 times upper limit of normal Renal function: creatinine ≤ upper limit of normal No uncontrolled infections, organ dysfunction, or severe mental illness ECOG performance status score of 0-2 and predicted survival ≥ 4 months No severe allergic constitution

Exclusion Criteria:

Allergy or contraindication to the study drug Pregnant or breastfeeding female patients Known history of alcohol or drug addiction (due to potential non-compliance) Mental illness or conditions preventing protocol compliance Less than 6 weeks after major organ surgery Liver function: ALT and AST > 2.5 times upper limit of normal; bilirubin > 2 times upper limit of normal Renal function: creatinine > upper limit of normal Deemed unsuitable for the clinical trial (poor compliance, substance abuse, etc.)

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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
Active Comparator: "3+7" Regimen; Idarubicin+cytarabine(IA) regimen or daunorubicin+cytarabine(DA) regimen for newly diagnosed AML.Recipients were randomized and those entering this group received IA or DA induction chemotherapy. With the IA regimen,recipients received idarubicin(8-10 mg/m2) for three days and cytarabine(75-100 mg/m2, every 12 hrs) for seven days. With the DA regimen,recipients received daunorubicin(60 mg/m2)for three days and cytarabine(75-100 mg/m2,every 12 hrs)for seven days.	Drug: "3+7"; IA regimen: Idarubicin (8-10 mg/m2) for 3 days . Cytarabine (75-100mg/m2, every 12 hrs) for 7 days. DA regimen: Daunorubicin(60 mg/m2) for 3 days. Cytarabine (75-100mg/m2, every 12 hrs) for 7 days.; Other Names: IA or DA
Experimental: Venetoclax Combined With CACAG Regimen; The CACAG+Venetoclax regimen has a total treatment period of 1 week, with a treatment cycle every 4 weeks, and a total of 1 course of treatment. Chidamide: 30 mg, twice a week, for a total of 2 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, continued until neutrophil recovery 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, when used in combination with azole drugs, the dosage is reduced to 100 mg/day.	Drug: Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor; Azacytidine (75 mg/m2/day, days 1 to 7). Cytarabine (75-100 mg/m2 bid, days 1 to 5). Aclacinomycin(20 mg/day, days 1,3,5). Chidamide (30 mg/day , days 1,4,8,11). Venetoclax (400 mg/day, days 1 to 14,Combined with posaconazole reduced to 100 mg/day,Combined with voriconazole reduced to 200 mg/day ). Granulocyte colony-stimulating factor (300 μg/day, day 0 until agranulocytosis recovery); Other Names: CACAG+VEN

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
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
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 109/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)
Overall Survival	Defined as the time from joining the clinical study to death due to any cause.	180 days after study 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).	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; Yantai Yuhuangding Hospital; Jining First People's Hospital; 940 Hospital of the People's Liberation Army Joint Logistic Support Force; 960th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2024
• Primary Completion (Actual): September 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: April 8, 2025
• First Submitted That Met QC Criteria: April 14, 2025
• First Posted (Actual): April 15, 2025

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Adjuvants, Immunologic; Lenograstim; Venetoclax; Cytarabine; Azacitidine; Aclacinomycins
• Other Study ID Numbers: KY-2024-3-40-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

This study plans to share individual participant data (IPD) with qualified researchers after trial completion. The data to be shared include:

Demographic information: Age, sex, race, etc. Treatment allocation: Assigned treatment group (e.g., venetoclax + CACAG regimen or "3+7" regimen).

Efficacy data: Primary and secondary endpoint data (e.g., complete remission rate, overall survival).

Safety data: Adverse events, serious adverse events, etc. Laboratory results: Hematological, biochemical parameters, and other biomarker data.

Follow-up data: Recurrence status and long-term outcomes during follow-up. Sharing Conditions Data will be shared in a de-identified format to protect participant privacy. Researchers must submit a formal request outlining the purpose and analysis plan.

Data use is restricted to research purposes only.

• IPD Sharing Time Frame: This study plans to share individual participant data (IPD) with qualified researchers after trial completion.

IPD Sharing Access Criteria

Data will be shared in a de-identified format to protect participant privacy. Researchers must submit a formal request outlining the purpose and analysis plan.

Data use is restricted to research purposes only.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No