Daunorubicin + Cytarabine + Venetoclax in de Novo AML

Daunorubicin Plus Cytarabine 3+5 Regimen Combined With Venetoclax in de Novo Patients With Acute Myeloid Leukemia: a Single Center, Open-label, Controlled Study

This study is a non-profit, prospective, single-center, open-label, controlled clinical trial aimed at evaluating the efficacy of the daunorubicin, cytarabine, and venetoclax (DAV) regimen in previously untreated adult AML patients eligible for intensive chemotherapy.The combination of daunorubicin administered for 3 consecutive days and cytarabine for 7 consecutive days constitutes the classic "3+7" induction chemotherapy regimen for AML patients eligible for chemotherapy. The addition of venetoclax to the "3+7" regimen has shown promising efficacy in newly diagnosed AML patients suitable for intensive therapy. However, this approach is associated with increased adverse reactions. Based on current clinical studies, we propose a modified approach involving reduced-dose chemotherapy combined with venetoclax for AML treatment, aiming to achieve optimal efficacy while effectively reducing adverse reactions.

Study Overview

• Status: Enrolling by invitation
• Conditions: Acute Myeloid Leukemia; Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: (Daunorubicin, Cytarabine, Venetoclax); Drug: (Daunorubicin, Cytarabine)

Detailed Description

PRIMARY OBJECTIVE:

1. To evaluate the efficacy of the regimen, as defined by complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete hematologic recovery (CRi), morphological leukemia-free state (MLFS), and partial remission (PR).

SECONDARY OBJECTIVES:

1. To evaluate the long-term effectiveness and durability of the treatment of the regimen, as defined by 1-year overall survival (OS), 1-year event-free survival (EFS), and duration of remission (DOR).
2. To evaluate the safety of the regimen, as defined by Grade 3-4 clinical adverse events (AEs), incidence of laboratory abnormalities, and treatment-related mortality (TRM).

OUTLINE:

• The regimen for the control group includes:(Daunorubicin, Cytarabine)

  • Daunorubicin: 60 mg/(m²·d) on days 1 to 3
  • Cytarabine: 100 mg/(m²·d) on days 1 to 7

• The experimental group's "DAV" regimen includes: (Daunorubicin, Cytarabine, Venetoclax)

  • Daunorubicin: 40 mg/(m²·d) on days 1 to 3
  • Cytarabine: 100 mg/(m²·d) on days 1 to 5
  • Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg from days 3 to 14
• The "DAV" regimen is designed to shorten the duration of induction chemotherapy while extending the application period of venetoclax, aiming to improve efficacy while reducing adverse effects.

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • Department of Hematology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:(All of the following criteria must be met.)

Patients with newly diagnosed AML based on FAB classification and flow cytometry standards who are eligible for intensive chemotherapy:

• Age between 18 and 59 years;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or 3;
• Expected survival time of ≥3 months;

• None of the following severe cardiac, pulmonary, hepatic, or renal conditions:

  • History of heart disease requiring treatment for congestive heart failure, or an ejection fraction ≤50%, or chronic stable angina;
  • Pulmonary diffusing capacity of carbon monoxide (DLCO) ≤65%, or forced expiratory volume in 1 second (FEV1) ≤65%;
  • Moderate liver impairment with total bilirubin >1.5 to ≤3.0 × the upper limit of normal (ULN);
  • Creatinine clearance ≥30 mL/min to <45 mL/min;
• Has not received radiotherapy, chemotherapy, targeted therapy, or hematopoietic stem cell transplantation within 4 weeks prior to enrollment;
• Has other comorbidities that, in the physician's judgment, make intensive chemotherapy unsuitable;
• Is capable of understanding and willing to sign the informed consent form for this study.

Exclusion Criteria:(Any of the following criteria will exclude the patient from participation)

• Presence of other malignancies;
• Prior treatment with venetoclax or azacitidine;
• History of angioplasty or stent placement within 12 months prior to signing the informed consent, or a history of myocardial infarction, unstable angina, or other clinically significant heart disease;
• Clinically uncontrolled active infection (including bacterial, fungal, or viral infections);
• Pregnant or breastfeeding women;
• Participation in any other clinical trial within 3 months prior to signing the informed consent;
• Any other condition that, in the investigator's judgment, makes the patient 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: Treatment(Daunorubicin, Cytarabine, Ventoclax); Treatment(Daunorubicin, Cytarabine, Ventoclax) See Detailed Description.	Drug: (Daunorubicin, Cytarabine, Venetoclax); Drugs：DaunorubicinDosage: 40 mg/(m²·d) on days 1 to 3Other names: Cerubidine, Daunomycin, Rubidomycin; Drugs：CytarabineDosage: 100 mg/(m²·d) on days 1 to 5Other names: Ara-C, Cytosine Arabinoside, Cytosar-U; Drugs：VenetoclaxDosage: 100 mg on day 1, 200 mg on day 2, and 400 mg from days 3 to 14Other names: ABT-199, Venclexta, Venclyxto
Active Comparator: Control(Daunorubicin, Cytarabine); Control(Daunorubicin, Cytarabine) See Detailed Description.	Drug: (Daunorubicin, Cytarabine); Drugs：DaunorubicinDosage: 60 mg/(m²·d) on days 1 to 3Other names: Cerubidine, Daunomycin, Rubidomycin; Drugs：CytarabineDosage: 100 mg/(m²·d) on days 1 to 7Other names: Ara-C, Cytosine Arabinoside, Cytosar-U

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Defined as the proportion of patients achieving complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete hematologic recovery (CRi), morphological leukemia-free state (MLFS), and partial remission (PR) occurring at the end of 2 cycles of treatment. Will be estimated along with the 95% credible interval. Patients who drop out of the study before completing 2 cycles and have been treated will be censored for the primary endpoint analysis.	End of cycle 2 (each cycle is 14 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival (OS) is defined as the time from randomization to death from any cause. Patients who are alive at the time of the last follow-up will be censored at the date of last contact. OS will be estimated using Kaplan-Meier methods, with median survival and 95% confidence intervals reported for each treatment group.	1-Year Follow-up
Event-free survival (EFS)	Event-Free Survival (EFS) is defined as the time from randomization to the first occurrence of disease progression, relapse, new cancer occurrence, or death from any cause. Patients who remain event-free at the last follow-up will be censored at the date of last contact. EFS will be estimated using Kaplan-Meier methods, with median EFS and 95% confidence intervals reported for each treatment group.	1-Year Follow-up
duration of remission (DOR)	Duration of Remission (DOR) is defined as the time from the first documentation of complete or partial remission until disease progression or relapse. Patients who remain in remission at the last follow-up will be censored at the date of last contact. DOR will be estimated using Kaplan-Meier methods, with median DOR and 95% confidence intervals reported for each treatment group.	1-Year Follow-up
Incidence of adverse events	Incidence of adverse events will be defined by Grade 3-4 clinical adverse events (AEs), incidence of laboratory abnormalities, and treatment-related mortality (TRM).	1-Year Follow-up

Collaborators and Investigators

• Sponsor: Anhui Medical University
• Collaborators: The First Affiliated Hospital of Anhui Medical University
• Investigators: Study Chair: ZhangBiao Long, Doctor, Department of Hematology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2025
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: November 12, 2024
• First Submitted That Met QC Criteria: November 18, 2024
• First Posted (Actual): November 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 10, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; 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; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Venetoclax; Cytarabine; Daunorubicin
• Other Study ID Numbers: PJ 2023-09-19

Plan for Individual participant data (IPD)

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

IPD Plan Description

Data Privacy and Ethical Restrictions: The individual participant data collected in this study involves sensitive information. Although de-identification processes have been applied, further measures are required to ensure compliance with relevant ethical standards and data privacy regulations, such as GDPR. We are currently working with ethical committees and relevant authorities to develop a compliant data-sharing strategy.

Data Quality and Preparation: The data has not yet undergone complete standardization and cleaning processes, and it may not meet the high-quality standards required for sharing. To ensure data accuracy and usability, we plan to consider data sharing once data processing and annotation are fully completed.

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