A Randomized Phase II Selection Trial of Venetoclax-Based Induction Intensity in Newly Diagnosed Acute Myeloid Leukemia

NCT07754799 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IIT2026079
• Study Type: interventional
• Target: 320
• Locations: 0 countries
• Sites: N/A

Brief Summary

This randomized, open label, multi arm phase II trial will evaluate the efficacy and safety of venetoclax based induction regimens of varying intensity (VA, VAM, or 2+5+V) versus standard 3+7 in fit patients aged ≥14 years with newly diagnosed AML. The trial is designed to select the optimal regimen as the experimental arm for a subsequent phase III randomized controlled trial. A total of 320 patients will be enrolled in this study，and segregated into four groups with 80 in each group. Patients who achieve CR/CRi/CRh after using different induction regimens will receive the same consolidation. Allogeneic hematopoietic stem cell transplantation is recommended for patients in the high-risk group or those with persist MRD positivity. After completion of the treatment phase, patients entered the follow-up period.

Conditions

Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  It is defined as the time from the start of randomization to the occurrence of induction failure or disease progression or death from any cause (whichever occurs first).

  up to 3 years

Secondary Outcomes (9)

• 30-day postinduction mortality

  up to 30 days

• 60-day postinduction mortality

  Up to 60 days

• Composite complete remission (CRc) rate

  Up to eight weeks

• Measurable Residual Disease (MRD) negative rate by flow cytometry

  Up to eight weeks

• Measurable Residual Disease (MRD) negative rate by molecular testing

  Up to approximately eight weeks

Study Arms (4)

3+7

ACTIVE COMPARATOR

Drug: daunorubicin daunorubicin: 60 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,

Drug: Daunorubicin; Drug: Cytarabine

VAM

EXPERIMENTAL

Drug: Liposome Mitoxantrone Liposome Mitoxantrone: 24 mg/m², administered by intravenous drip (ivgtt) on day 1, every 4 weeks Drug: Venetoclax Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14, administered orally (po), every 4 weeks Drug: Azacitidine Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7,

Drug: Liposome Mitoxantrone; Drug: Venetoclax; Drug: Azacitidine

VA

EXPERIMENTAL

Drug: Venetoclax Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-21, administered orally (po). Bone marrow examination is performed on day 21. If blasts \>5%, then venetoclax 400 mg is continued on days 21-28. Drug: Azacitidine Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7,

Drug: Azacitidine; Drug: Venetoclax

2+5+V

EXPERIMENTAL

Drug: daunorubicin daunorubicin: 60 mg/m2, administered by intravenous drip (ivgtt) on days 1-2, every 4 weeks Drug: Cytarabine Cytarabine: 100 mg/m2, administered by intravenous drip (ivgtt) on days 1-5, every 4 weeks Drug: Venetoclax Venetoclax: 100 mg on day 3, 200 mg on day 4, and 400 mg on days 5-11, administered orally (po)

Drug: Daunorubicin; Drug: Cytarabine; Drug: Venetoclax

Interventions

Liposome Mitoxantrone DRUG

Liposome Mitoxantrone: 24 mg/m², administered by intravenous drip (ivgtt) on day 1,

VAM

Azacitidine DRUG

Azacitidine: 75 mg/m², administered subcutaneously (sc) on days 1-7,

VA; VAM

Daunorubicin DRUG

daunorubicin: 60 mg/m2, administered by intravenous drip (ivgtt) on days 1-3,

3+7

Cytarabine DRUG

Cytarabine: 100 mg/m2, administered by intravenous drip (ivgtt) on days 1-7,

3+7

Venetoclax DRUG

Venetoclax: 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3-14, administered orally (po),

VAM

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AML per WHO (2022) or ICC criteria, and MDS/AML as defined by ICC (with bone marrow blast percentage of 10%-20%).
• Age ≥14 years, male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Judged by the investigator to be suitable for intensive induction chemotherapy and expected to tolerate the treatment intensity specified in the protocol.
• Meet the following laboratory test requirements (assessed within 7 days prior to treatment):
• Total bilirubin ≤1.5 × upper limit of normal (ULN) for the same age group;
• AST and ALT ≤2.5 × ULN for the same age group;
• Serum creatinine \<2 × ULN for the same age group;
• Cardiac enzymes \<2 × ULN for the same age group;
• Cardiac ejection fraction determined by echocardiography (ECHO) within the normal range.
• Written informed consent must be signed before any study specific procedures are initiated, by the patient themselves or by their immediate family members. If, in consideration of the patient's medical condition, signing by the patient themselves would be detrimental to their treatment, the informed consent may be signed by the legally authorized representative or the patient's immediate family members.

You may not qualify if:

• Acute promyelocytic leukemia with PML-RARA fusion gene.
• Acute myeloid leukemia with RUNX1-RUNX1T1 or CBFB-MYH11 fusion gene.
• Acute myeloid leukemia with BCR-ABL fusion gene.
• Presence of FLT3 mutation (these patients are recommended to be enrolled in clinical trials of FLT3 inhibitors).
• Patients who have previously received induction chemotherapy (however, cytoreductive therapy such as hydroxyurea is permitted).
• Concurrent malignancy of other organs that requires treatment.
• Active cardiac disease, defined as one or more of the following:
• History of uncontrolled or symptomatic angina pectoris;
• Myocardial infarction within 6 months prior to study enrollment;
• History of arrhythmia requiring medication or with clinically significant symptoms;
• Uncontrolled or symptomatic congestive heart failure (\> NYHA class 2).
• Serious infectious diseases (e.g., active tuberculosis, pulmonary aspergillosis).
• Patients deemed unsuitable for enrollment by the investigator.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Daunorubicin; Cytarabine; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aza Compounds; Ribonucleosides

Central Study Contacts

Hui Wei, MD

CONTACT

022-23608456; weihui@ihcams.ac.cn

Miao Yang, MD

CONTACT

022-23608341; yangmiao@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: August 10, 2026
• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2029
• Last Updated: August 10, 2026

Record last verified: 2026-07