Efficacy of Venetoclax Combined With Intensive Chemotherapy in Different Subgroups of AML (DAV-AML-2024)

Efficacy of Venetoclax Combined With Intensive Chemotherapy in Different Subgroups of Acute Myeloid Leukemia : a Multi-center, Single-arm Clinical Trial

Acute myeloid leukemia (AML) is a common hematological malignancy. Intensive chemotherapy is the main treatment in fit patients.

Retrospective studies have shown that Venetoclax is highly effective in elder AML patients with IDH2 and NPM1 mutations while in those with TP53 and FLT3 mutations, the combination of azacitidine with Venetoclax showed an increased remission rate without improved survival.

Since AML is a highly heterogeneous disease, it is not clear which genetic type of adult AML patients would benefit from Venetoclax combined with intensive chemotherapy.

Therefore, this study intends to conduct a phase II clinical trial to investigate the efficacy of intensive chemotherapy combined with Venetoclax in adult AML patients, and reveal the efficacy of Venetoclax added to chemotherapy regimens for AML with different cytogenetic and molecular subgroups.

Study Overview

• Status: Recruiting
• Conditions: AML (Acute Myelogenous Leukemia)
• Intervention / Treatment: Drug: Daunorubicin; Drug: Cytarabine; Drug: Venetoclax; Drug: Azacitidine

Detailed Description

Patients will receive 1 course of intensive chemotherapy combined with venetoclax for induction and those who achieved complete remission will receive 3 courses of intermediate-dose cytarabine combined with Venetoclax for consolidation. After consolidation therapy, Venetoclax in combination with azacitidine will be applied for 6 courses as maintenance treatment. Allogeneic hematopoietic stem cell transplantation is recommended for high-risk groups and intermediate-risk with positive measurable residual disease.

• Study Type: Interventional
• Enrollment (Estimated): 380
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hui Wei, MD; Phone Number: 13132507161; Email: weihui@ihcams.ac.cn

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients who meet AML according to WHO (2022) or AML and MDS/AML defined by ICC standards.
2. Age ≥14 years old, ≤ 60 years old, male or female.
3. The physical status assessment (ECOG-PS) of the Eastern Oncology Collaboration group was 0-2 points.

4. Fulfill the requirements of the following laboratory tests (performed within 7 days prior to treatment) :

   1. Total bilirubin ≤ 1.5 times the upper limit of normal value (same age);
   2. AST and ALT≤ 2.5 times the upper limit of normal value (same age);
   3. Blood creatinine < 2 times the upper limit of normal (same age);
   4. Myocardial enzymes < 2 times the upper limit of normal (same age);
   5. Left ventricular ejection fraction >50% by measure of echocardiogram (ECHO). Informed consent must be signed before the commencement of all specific study procedures, and signed by the patient himself or his immediate family. Considering the patient's condition, if the patient's signature is not conducive to the treatment of the condition, the informed consent shall be signed by the legal guardian or the patient's immediate family.

Exclusion Criteria:

Subjects who meet any of the following criteria are excluded from the study:

1. Acute promyelocytic leukemia with PML-RARA fusion gene
2. Acute myeloid leukemia with BCR-ABL fusion gene
3. Treated patients (but can receive hydroxyurea or cytarabine to the lower tumor burden).
4. Concurrent malignant tumors of other organs (those requiring treatment).

5. Active heart disease, defined as one or more of the following:

   1. A history of uncontrolled or symptomatic angina;
   2. Myocardial infarction less than 6 months after enrollment;
   3. Have a history of arrhythmia requiring drug treatment or severe clinical symptoms;
   4. Uncontrolled or symptomatic congestive heart failure (> NYHA level 2);
6. Serious infectious diseases (uncured tuberculosis, pulmonary aspergillosis).
7. Those who were not considered suitable for inclusion by the researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: venetoclax combined with intensive chemotherapy; Induction therapy: daunorubicin, cytarabine, combined with venetoclax for 1 course. Consolidation therapy: cytarabine combined with venetoclax for 3 courses. Maintenance therapy: azacitidine combined with venetoclax for 6 courses.	Drug: Daunorubicin; 60mg/m2/d d1-3 in Induction therapy; Drug: Cytarabine; Cytarabine 100mg/m2/d d1-7 in Induction therapy, 2g/m2 q12h d1-3 in Consolidation therapy; Drug: Venetoclax; 100mg d-2, 200mg d-1, 400mg d1-7 in Induction therapy, 400mg d1-7 in Consolidation therapy and Maintenance treatment; Drug: Azacitidine; 75mg/m2/d d1-5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	All patients definitions for the trial; From the date of enrollment to the time of treatment failure after two courses of induction therapy, recurrence after CRc, date of all-cause death, or the date of last survival follow-up.	up to 2 years after the date of the last enrolled participants

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) with negative MRD detected by flow cytometry	The ratio of CR/CRh/CRi with negative MRD detected by flow cytometry after induction, consolidation, and maintenance therapy.	up to 1 years after the date of the last enrolled participants
CR/CRh/CRi with negative MRD detected by PCR	The ratio of CR/CRh/CRi with negative MRD detected by PCR after induction, consolidation, and maintenance therapy.	up to 1 years after the date of the last enrolled participants
overall survival (OS)	Used to evaluate all patients who enter clinical trials. From the date of entry into the trial until the date of patient death (including any cause) or last survival follow-up.	up to 2 years after the date of the last enrolled participants
30-day mortality	Percentage of patients who died within 30 days from enrollment.	within 30 days of the date of the last enrolled participants
60-day mortality	Percentage of patients who died within 60 days from enrollment.	within 60 days of the date of the last enrolled participants
Complete remission (CR)/CR with partial hematologic recovery (CRh)/CR with incomplete hematologic recovery (CRi) rate	The ratio of patients achieved CR/CRh/CRi after two courses of induction therapy.	up to 3 months after the date of the last enrolled participants
Relapse-free survival (RFS)	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; patients not known to have relapsed or died at last follow-up are censored on the date they were last known to be alive	up to 2 years after the date of the last enrolled participants

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: September 27, 2024
• First Submitted That Met QC Criteria: October 8, 2024
• First Posted (Actual): October 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: May 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; 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; Cytarabine; Azacitidine; Daunorubicin; venetoclax
• Other Study ID Numbers: IIT2024074

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