Chidamide, Venetoclax, and Azacitidine for Newly Diagnosed Acute Myeloid Leukemia

A Multicenter, Randomized, Controlled Clinical Trial of Chidamide Combined With Venetoclax and Azacitidine in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) Who Are Not Suitable for Intensive Chemotherapy

To evaluate the feasibility, effectiveness and safety of chidamide combined with venetoclax and azacitidine in the treatment of newly diagnosed acute myeloid leukemia (AML) who are not suitable for intensive chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; AML
• Intervention / Treatment: Drug: Chidamide; Drug: Venetoclax; Drug: azacitidine

• Study Type: Interventional
• Enrollment (Estimated): 184
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jianxiang Wang, Medical PhD; Phone Number: 022-23909273; Email: wangjx@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Blood Hospital
      • Contact: hui wei, MD; Phone Number: 86-13132507161; Email: weihui@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• （1）Age ≥18 years old, no gender limit ;
• （2）be diagnosed with AML (non-M3) according to WHO 2016 standards;
• （3）No previous treatment;
• （4）Ineligible for intensive chemotherapy based on the following definitions: ≥75 years of age or 18 to 74 years of age with at least one of the following comorbidities: Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3 A history of cardiac disease such as congestive heart failure Treatment is required, or ejection fraction ≤ 50%, or chronic stable angina, diffusing capacity of lung for carbon monoxide (DLCO) ≤ 65%, or forced expiratory volume in first second (FEV1) ≤ 65%, creatinine clearance ≥ 30 mL/min to < 45 mL/min, moderate hepatic impairment, total bilirubin > 1.5 to ≤ 3.0 × ULN, other comorbidities that are not suitable for intensive chemotherapy in the physician's judgment.
• （5）Subjects must have an ECOG performance status score of: 0 to 2 for subjects aged ≥ 75 years or 0 to 3 for subjects aged ≥ 18 to 74 years.
• （6）Other comorbidities that are not suitable for intensive chemotherapy in the doctor's judgment;
• （7）Expected survival time ≥3 months;
• （8）Have the ability to understand and be willing to sign the informed consent form for this study.

Exclusion Criteria:

• (1) Combined with other malignant tumors
• (2) Have ever received treatment with chidamide and / or venetoclax or azacitidine;
• (3) The risk is assessed as low risk according to the NCCN 2022 guidelines [t(8;21)(q22;q22.1);RUNX1-RUNX1T1, inv(16)(p13.1q22) or t(16;16 )(p13.1;q22);CBFB-MYH11 ] ;
• (4) The subject is known to have AML central nervous system (CNS) infiltration;
• (5) Have undergone cardiac angioplasty or stent placement within 12 months before signing the informed consent form , or have a history of myocardial infarction, unstable angina, or other clinically significant heart disease;
• (6 ) Active infections (including bacterial, fungal or viral infections) and organ bleeding that cannot be controlled clinically;
• (7) Pregnant or lactating women;
• (8) Participated in any other clinical research within 3 months before signing the informed consent form ;
• (9 ) The researcher believes that it is not suitable to participate in this study;

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: Chidamide combined with venetoclax, azacitidine group; Chidamide (C): 30 mg/d orally on d1, 4, 8, 11 or 10 mg QD, d1-d14, adjusted according to patient tolerance Azacitidine (A): 75 mg/m 2 /d subcutaneous injection d1-d7 Venetoclax (V): 100 mg d1 200 mg d 2 400 mg d3-d28 Orally A treatment cycle is 28 days , and subjects will continue to receive treatment allocation according to the investigator's assessment until documented disease progression, intolerable toxicity, withdrawal of consent, or the subject meets other conditions for terminating treatment. Program Standards (whichever occurs first).	Drug: Chidamide; 30 mg/d orally twice-weekly; Drug: Venetoclax; 100 mg d1 200 mg d 2 400 mg d3-d28 Orally; Drug: azacitidine; 75 mg/m 2 /d subcutaneous injection or IV d1-d7
Active Comparator: venetoclax, azacitidine group; azacitidine: 75 mg/m 2 /d subcutaneous injection d1-d7 Venetoclax: 100 mg day 1, 200 mg day 2, 400 mg day 3-d28 orally A treatment cycle is 28 days , and subjects will continue to receive treatment allocation according to the investigator's assessment until documented disease progression, intolerable toxicity, withdrawal of consent, or the subject meets other conditions for terminating treatment. Program Standards (whichever occurs first).	Drug: Venetoclax; 100 mg d1 200 mg d 2 400 mg d3-d28 Orally; Drug: azacitidine; 75 mg/m 2 /d subcutaneous injection or IV d1-d7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite complete remission rate	Composite complete remission rate after 2 cycles of treatment [Complete remission, CR) + complete remission with incomplete blood count (CR with incomplete blood count recovery, CRi); CR + CRi ]	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Overall response rate (ORR), including complete remission (Complete remission (CR), complete remission with incomplete blood count (CR with incomplete blood count recovery (CRi), morphological leukemia free state (MLFS), and partial remission (PR) as a percentage of the total number of patients participating in the efficacy analysis.	24months
Overall survival (OS)	Overall survival (OS): defined as the number of days from the date of randomization to the date of death. Subjects who have not died will be censored on the last date they are known to be alive .	24months
MRD response rate	Minimal residual disease (MRD)rate: defined as less than 0.1% remaining blasts per white blood cell, as measured by bone marrow examination. Other thresholds can also be explored and correlated with efficacy results. Subjects who are randomized but not assessed for MRD will be considered MRD response rate non-responders. The proportion of subjects achieving an MRD response (CR + CRi) was calculated.	24months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Jianxiang Wang, MD, Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): August 3, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Venetoclax; Azacitidine
• Other Study ID Numbers: IIT2023074

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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