Study on the Efficacy and Safety of VA Regimen Compared to "3+7" Regimen in Newly Diagnosed AML With NPM1 or IDH1/IDH2 Mutations

NCT07664839 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: NPM1/IDH-AML01
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, multicenter, randomized, open-label, non-inferiority clinical study aims to compare the efficacy and safety of VA regimen (venetoclax combined with azacitidine) versus conventional "3+7" chemotherapy regimen in adult patients aged 18 to 65 years with newly diagnosed acute myeloid leukemia (AML) carrying NPM1, IDH1 or IDH2 gene mutations. The primary goal of this trial is to check whether the VA treatment can reach a non-inferior composite complete remission rate at the end of the induction treatment cycle, which is the key primary endpoint of this research. Several secondary clinical outcomes will also be evaluated in this study, including the rate of minimal residual disease (MRD) negativity after remission, duration of remission, 1-year event-free survival rate and 1-year overall survival rate of enrolled patients. In addition, the safety and treatment-related side effects occurring during the whole induction treatment phase will be systematically collected and compared between two groups as another important secondary assessment. Eligible enrolled participants will be randomly split into two study groups: patients in experimental group will receive venetoclax plus azacitidine (VA regimen), while patients in control group will receive standard "3+7" induction chemotherapy following conventional clinical protocol. All subjects will complete regular disease assessment, laboratory examinations and scheduled follow-up visits as required by trial design during treatment and post-treatment observation period. Researchers will collect and analyze all above clinical outcome data from all participants, to verify the non-inferior efficacy and relative safety of VA regimen for this specific subtype of newly diagnosed AML patients.

Conditions

Acute Myeloid Leukemia; NPM1 Mutation; IDH1 Mutation; IDH2 Mutation

Keywords

Acute myeloid leukemia; Venetoclax; NPM1 mutation; IDH1 mutation; IDH2 mutation

Outcome Measures

Primary Outcomes (1)

• Composite complete remission rate at the end of induction cycle

  At the end of 1-2 induction treatment cycles (each cycle is 28 days)

Secondary Outcomes (7)

• Composite Complete Remission

  At the end of 1-2 induction treatment cycles (each cycle is 28 days)

• Minimal residual disease (MRD) negative rate after remission

  At the end of induction cycle (each cycle is 28 days)

• Duration of Response (DoR)

  From date of confirmed complete response (CR) until documented disease relapse or death from any cause, assessed up to 24 months after randomization

• 1-year Event-Free Survival (EFS) rate

  From date of randomization until first documented treatment failure, relapse, or death from any cause, assessed up to 24 months after randomization; 1-year rate calculated at 12 months post-randomization

• 1-year Overall Survival (OS) rate

  From date of randomization until death from any cause, assessed up to 24 months after randomization; 1-year rate calculated at 12 months post-randomization

Other Outcomes (4)

• Correlation between baseline AML gene mutation status detected by next-generation sequencing and anti-leukemic efficacy endpoints (complete remission rate, MRD-negative rate, 1-year recurrence-free survival rate) in VA regimen arm

  From date of randomization up to 24 months after randomization, biomarker-efficacy correlation analysis will be performed using clinical data collected within the first 12 months post randomization

• Hospitalization duration during induction therapy

  From the date of induction therapy initiation through completion of the first induction cycle (each cycle is 28 days)

• Transfusion volume during induction therapy

  From the date of induction therapy initiation through completion of the first induction cycle (each cycle is 28 days)

Study Arms (2)

Venetoclax plus Azacitidine (VA regimen)

EXPERIMENTAL

1. Venetoclax: oral administration, specified dosage and schedule for induction cycle; 2. Azacitidine: subcutaneous/intravenous injection with standard induction dose and treatment cycle per clinical protocol.

Drug: VEN combined with azacitidine

"3+7" induction chemotherapy

ACTIVE COMPARATOR

Standard 3+7 induction chemotherapy (Cytarabine continuous infusion for 7 days plus Anthracycline intravenous infusion for 3 days) following routine clinical induction regimen for AML.

Drug: Cytarabine plus Daunorubicin

Interventions

VEN combined with azacitidine DRUG

Venetoclax,oral targeted anti-BCL-2 agent and Azacitidine,hypomethylating agent, given via injection for experimental VA arm only

Venetoclax plus Azacitidine (VA regimen)

Cytarabine plus Daunorubicin DRUG

Cytarabine,continuous intravenous infusion for total 7 days and Daunorubicin,Intravenous anthracycline chemotherapy administered for 3 days,in standard 3+7 induction regimen

"3+7" induction chemotherapy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 65 years old ≥ 18 years old;
• Diagnosed as acute myeloid leukemia (non APL) (diagnostic criteria refer to the 2022 ELN classification system);
• Initial diagnosis accompanied by NPM1 mutations (A, B, D types and rare types are all acceptable) and/or IDH1/IDH2 mutations;
• Have not received any other induction therapy before (except hydroxyurea);
• Physical fitness status score (ECOG PS) 0-3;
• Having sufficient organ function, defined as follows:
• Liver function: serum total bilirubin ≤ 3 x upper limit of normal range (ULN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3 x ULN, unless considered to be caused by leukemia;
• Renal function: endogenous creatinine clearance rate ≥ 30ml/min;
• Heart function: NYHA classification ≤ 2 points;
• Participants must have the ability to understand and be willing to participate in this study, and sign an informed consent form.

You may not qualify if:

• Acute promyelocytic leukemia;
• Merge extramedullary infiltration such as central nervous system leukemia;
• Have a clear history of CMML or MDS, and later progress to AML; Or have a history of malignant tumors;
• There is uncontrolled active infection (including bacterial, fungal, or viral infections);
• Pregnant or lactating women;
• Researchers determine that participants are not suitable to participate in this experiment

Sponsors & Collaborators

• Shen yang: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; Cytarabine; Daunorubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Yang Shen, MD

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yang Shen, MD

CONTACT

+86-021-64370045; sy_clinicaltrial@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician, Professor, Department of Hematology

Study Record Dates

• First Submitted: June 10, 2026
• First Posted: June 24, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2032
• Last Updated: June 24, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)