Venetoclax, Azacitidine, and Mitoxantrone Hydrochloride Liposome Versus Idarubicin and Cytarabine in Newly Diagnosed AML

A Prospective, Multicenter, Randomized Controlled Clinical Study of Venetoclax Combined With Azacitidine and Mitoxantrone Hydrochloride Liposome Versus Idarubicin Combined With Cytarabine "3+7" in the Treatment of Newly Diagnosed AML

This study aims to evaluate the efficacy and safety of venetoclax combined with azacitidine and mitoxantrone hydrochloride liposome (MVA) versus idarubicin combined with cytarabine (IA) in the treatment of newly diagnosed AML.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: Mitoxantrone Hydrochloride Liposome; Drug: Venetoclax; Drug: Azacitidine; Drug: Idarubicin; Drug: Cytarabine

Detailed Description

For adult patients with newly diagnosed acute myeloid leukemia (AML) who are eligible for intensive chemotherapy, the standard intensive induction regimen remains anthracycline combined with cytarabine. However, the efficacy of traditional intensive chemotherapy is limited in high-risk AML and is associated with significant myelosuppression and infection risk, underscoring the need for novel therapeutic strategies. This study was therefore designed as a prospective, multicenter, randomized controlled trial. The study plans to enroll 204 adults with newly diagnosed AML. Participants will be randomized in a 2:1 ratio to receive induction therapy with either: 1) venetoclax, azacitidine, and mitoxantrone hydrochloride liposome (MVA), or 2) idarubicin and cytarabine (IA). The primary endpoint is the composite complete remission (CRc) rate following one cycle of induction therapy.

• Study Type: Interventional
• Enrollment (Estimated): 204
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiaowen Tang; Phone Number: 0512-67780103; Email: tangxiaowen@suda.edu.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
      • Principal Investigator: Mingzhen Yang
  • Henan
    • Luoyang, Henan, China, 41003
      • The First Affiliated Hospital of Henan University of Science And Technology
      • Principal Investigator: Ling Qin
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Principal Investigator: Zhenya Hong
    • Wuhan, Hubei, China
      • Renmin Hospital of Wuhan University
      • Principal Investigator: Baixin Ye
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Changzhou First People's Hospital
      • Principal Investigator: Weiying Gu
    • Huai'an, Jiangsu, China, 223002
      • Huai'an Second People's Hospital
      • Principal Investigator: Yanming Zhang
    • Jingjiang, Jiangsu, China, 214500
      • Jingjiang People's Hospital
      • Principal Investigator: Miao Sun
    • Lianyungang, Jiangsu, China, 222002
      • The First People's Hospital of Lianyungang
      • Principal Investigator: Ying Wang
    • Lianyungang, Jiangsu, China, 222006
      • The Second People's Hospital of Lianyungang
      • Principal Investigator: Wanchuan Zhuang
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
      • Principal Investigator: Kourong Miao
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital of Chinese Medicine
      • Principal Investigator: Xuejun Zhu
    • Nantong, Jiangsu, China, 226001
      • Affiliated Hospital of Nantong University
      • Principal Investigator: Zenghua Lin
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
      • Principal Investigator: Depei Wu
      • Contact: Xiaowen Tang
    • Wuxi, Jiangsu, China, 214023
      • Wuxi People's Hospital
      • Principal Investigator: Yuanqiang Jiang
    • Yancheng, Jiangsu, China, 224006
      • YanCheng NO.1 People's Hospital
      • Principal Investigator: Yuexin Cheng
    • Yangzhou, Jiangsu, China, 225001
      • Northern Jiangsu People's Hospital
  • Shandong
    • Jinan, Shandong, China
      • Shandong First Medical University Affiliated Tumor Hospital
      • Principal Investigator: Ji Ma
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
      • Principal Investigator: Yamin Tan
    • Ningbo, Zhejiang, China, 315010
      • The First Affiliated Hospital of Ningbo University
      • Principal Investigator: Guifang Ouyang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. The patient fully understands the study, voluntarily participates, and has signed the informed consent form (ICF).

  2. Aged 18 to 65 years, any gender. 3. Newly diagnosed with AML according to the 2022 WHO classification. 4. Eligible for intensive chemotherapy as determined by the investigator. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 6. Life expectancy ≥ 3 months. 7. Adequate liver and renal function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) (≤ 5 × ULN for patients with hepatic involvement); total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients with hepatic involvement); serum creatinine ≤ 1.5 × ULN.

Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded from the study:

  1. Any of the following conditions:

     1. Acute promyelocytic leukemia (APL);
     2. Central nervous system leukemia (CNSL);
     3. AML secondary to chemotherapy/radiotherapy for other malignancies or antecedent hematological disorders (e.g., MDS, MPN, CML);
  2. Prior treatment with hypomethylating agents (HMA) or venetoclax;
  3. Prior anti-AML therapy (except for leukocytosis management such as hydroxyurea or leukapheresis);
  4. History of other malignancies within the past 5 years (except for cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, or other malignancies that have been effectively controlled without treatment in the past five years);
  5. Inability to take oral medication or malabsorption syndrome;

  6. Cardiac function or disease meeting any of the following criteria:

     1. Long QTc syndrome or QTc interval > 480 ms;
     2. Complete left bundle branch block, second- or third-degree atrioventricular block;
     3. Severe, uncontrolled arrhythmias requiring medication;
     4. New York Heart Association (NYHA) Class ≥ II;
     5. Left ventricular ejection fraction (LVEF) < 50%;
     6. History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia, or any other significant arrhythmia requiring treatment, clinically significant pericardial disease within 6 months prior to enrollment, or ECG evidence of acute ischemia or active conduction system abnormalities.
  7. Uncontrolled systemic illnesses (e.g., active infection, uncontrolled hypertension, diabetes);
  8. Human Immunodeficiency Virus (HIV) infection (HIV antibody positive);
  9. Active Hepatitis B or C infection (Hepatitis B: HBsAg or HBcAb positive, with HBV-DNA > 1×10³ copies/mL; Hepatitis C: HCV-Ab positive, with HCV-RNA > 1×10³ copies/mL);
  10. Known history of immediate or delayed hypersensitivity reaction to drugs of the same class or excipients of the investigational product;
  11. Significant neurological or psychiatric history;
  12. Pregnant or lactating women;
  13. Patients considered by the investigator to be unsuitable for participation 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: MVA; Patients achieving complete remission (CR), CR with partial hematologic recovery (CRh), CR with incomplete hematologic recovery (CRi), or morphologic leukemia free state (MLFS) after Cycle 1 proceed to consolidation therapy. Patients achieving a partial response (PR) or demonstrating 50% blast reduction after Cycle 1 receive one additional cycle of re-induction with the same MVA regimen. Those who subsequently achieve CR, CRh, CRi, or MLFS after Cycle 2 proceed to consolidation. Patients with no response (NR) after Cycle 1, or those with NR or PR after Cycle 2, will discontinue study treatment.	Drug: Mitoxantrone Hydrochloride Liposome; Mitoxantrone Hydrochloride Liposome: 24 mg/m², administered by intravenous drip (ivgtt) on day 1; Drug: Venetoclax; Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-9, administered orally (po); Drug: Azacitidine; Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7
Active Comparator: IA; Patients achieving CR, CRh, CRi, or MLFS after Cycle 1 proceed to consolidation therapy. Patients achieving a PR or demonstrating 50% blast reduction after Cycle 1 receive one additional cycle of re-induction with the same IA regimen. Those who subsequently achieve CR, CRh, CRi, or MLFS after Cycle 2 proceed to consolidation. Patients with NR after Cycle 1, or those with NR or PR after Cycle 2, will discontinue study treatment.	Drug: Idarubicin; Idarubicin: 12 mg/m², administered by intravenous drip (ivgtt) on days 1-3; Drug: Cytarabine; Cytarabine: 100 mg/m², administered by intravenous drip (ivgtt) on days 1-7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite Complete Remission(CRc) rate after one cycle of induction therapy	Complete remission plus complete remission with partial hematologic recovery plus complete remission with incomplete hematologic recovery (CR+CRh+CRi). Response is assessed according to the the European LeukemiaNet (ELN) 2022 criteria.	At the end of the first treatment cycle (Day 28 ± 7), each cycle is 28 days).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurable residual disease (MRD) negativity rate (by flow cytometry and molecular testing) among patients who achieved CRc after induction therapy	Percentage of participants who achieve a CRc MRD- as defined by investigators based on ELN 2022 criteria.	At the end of each cycle (Day 28 ± 7), each cycle is 28 days, up to 2 cycles.
Overall response rate(ORR) to induction therapy	CRc+morphologic leukemia-free state (MLFS)+partial remission (PR). Response is assessed according to the the European LeukemiaNet (ELN) 2022 criteria.	At the end of each cycle (Day 28 ± 7), each cycle is 28 days, up to 2 cycles
Time to CRc	Defined as the time from day 1 of the treatment until the patient achieves CRc. Response is assessed according to the the European LeukemiaNet (ELN) 2022 criteria.	Within 100 days from day 1 of treatment.
1-year relapsed-free survival (RFS) rate	Defined only for patients achieving CRc. Measured from the date of achievement of remission until the date of hematologic relapse or death from any cause.	up to 1 years after the date of the last enrolled participants
1-year leukemia-free survival (LFS) rate	Defined only for patients achieving CRc. Measured from day 1 of treatment to the date of first documented leukemia relapse or death from any cause.	up to 1 years after the date of the last enrolled participants
1-year overall survival (OS) rate	Defined for all patients in the study. Measured from day 1 of treatment to the date of death from any cause.	up to 1 years after the date of the last enrolled participants
Incidence of treatment-emergent adverse events, transfusion volume and time to hematologic recovery	Safety assessments included adverse events (graded by NCI CTCAE v5.0), the number of units of red blood cells and platelets transfused, time to neutrophil recovery to ≥0.5x10⁹/L, and time to platelet recovery to ≥20x10⁹/L.	From day 1 of treatment to 28(±7) days after the last dose
Change in Health-Related Quality of Life Assessed by EQ-5D-5L	EuroQol 5-Dimension 5-Level (EQ-5D-5L) is a standardized instrument for measuring generic health-related quality of life. It comprises a descriptive system (generating a health utility score for cost-utility analysis) and a Visual Analogue Scale (EQ VAS) recording the participant's self-rated health. Recommended assessment time points: Baseline, end of Cycle 1 induction therapy (Day 28 ± 7, assessable after completion of bone marrow aspiration), end of Cycle 2 induction therapy (Day 28 ± 7), end of consolidation therapy, first follow-up after transplantation, and follow-up after first relapse.	up to 1 years after the date of the last enrolled participants
Change in Cancer-Specific Quality of Life Assessed by EORTC QLQ-C30	The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a cancer-specific instrument. It includes a Global Health Status/Quality of Life scale, five functional scales (physical, role, emotional, cognitive, social), and nine symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). Recommended assessment time points: Baseline, end of Cycle 1 induction therapy (Day 28 ± 7, assessable after completion of bone marrow aspiration), end of Cycle 2 induction therapy (Day 28 ± 7), end of consolidation therapy, first follow-up after transplantation, and follow-up after first relapse.	up to 1 years after the date of the last enrolled participants
Total Direct Medical Costs	Total direct medical costs (including costs of study drugs, concomitant medications, hospitalization, outpatient visits, laboratory tests, and management of adverse events) incurred over the study period. Costs will be estimated based on patient-level resource utilization data collected during the trial and, if applicable, extrapolated using a long-term simulation model. Unit of Measure: Currency (CNY)	up to 1 year after the date of the last enrolled participant
Quality-Adjusted Life Years (QALYs)	Quality-adjusted life years gained, calculated by integrating survival data with health utility weights derived from the EQ-5D-5L questionnaire administered at specified time points during the trial. A long-term simulation model may be used to extrapolate QALYs beyond the observation period. Unit of Measure: Years	up to 1 year after the date of the last enrolled participant

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
• Investigators: Principal Investigator: Depei Wu, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): March 10, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 22, 2025
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Idarubicin; Cytarabine; Venetoclax; Azacitidine; Acute myeloid leukemia; mitoxantrone hydrochloride liposome
• 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; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Arabinonucleosides; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Cytarabine; Azacitidine; Idarubicin; venetoclax
• Other Study ID Numbers: CSPC-DED-AML-K23

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