Metformin Inhibits DNMT3A Clonal Hematopoiesis in Acute Leukemia

NCT07188740 | Not Yet Recruiting Phase 1

• 1 other identifier: IIT2025104
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, single-arm clinical study evaluating the efficacy and safety of metformin in inhibiting DNMT3A R882-driven clonal hematopoiesis (CH) in patients with acute leukemia (AL) who are in remission and under follow-up. Patients with DNMT3A R882 mutation (VAF ≥5%) will receive oral metformin for 6 months, with dosage gradually increased to 2000 mg/day. The primary endpoint is the proportion of patients with effective decline in DNMT3A R882 mutation VAF at 6 months. Secondary endpoints include VAF decline at 3 months, relapse-free survival (RFS) at 6 and 12 months, overall survival (OS), cumulative incidence of relapse (CIR), cumulative remission-phase mortality, and adverse event rates. Planned enrollment: 30 participants.

Conditions

DNMT3A Gene Mutation

Keywords

CHIP; acute leukemia; Metformin; DNMT3A

Outcome Measures

Primary Outcomes (1)

• DNMT3A R882 Mutation VAF at 6 Months

  Effective decline defined as: For baseline VAF \>20%, absolute decline ≥10%; for VAF ≤20%, relative decline ≥50%. Measured via NGS.

  up to 6 months

Secondary Outcomes (6)

• DNMT3A R882 Mutation VAF at 3 Months

  up to 3 months

• Relapse-Free Survival (RFS) Rate at 6 Months

  up to 6 months

• Relapse-Free Survival (RFS) Rate at 12 Months

  up to 12 months

• Overall Survival (OS) Rate

  Up to 12 months

• Cumulative Incidence of Relapse (CIR)

  Up to 12 months

Study Arms (1)

Metformin Treatment Arm

EXPERIMENTAL

Dosage: Start at 500 mg twice daily, titrate to 2000 mg/day (e.g., 500 mg three times daily or 1000 mg twice daily), based on tolerance.

Drug: Metformin

Interventions

Metformin DRUG

Start at 500 mg twice daily, titrate to 2000 mg/day for 6 months

Metformin Treatment Arm

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:

• Patients diagnosed with acute leukemia based on bone marrow morphology, immunology, and genetics, per WHO 2022 or ICC criteria.
• Patients in complete remission follow-up phase with DNMT3A R882 mutation clonal hematopoiesis, VAF ≥5%.
• Age ≥14 years, any gender
• Laboratory requirements (within 7 days before treatment):
• Total bilirubin ≤1.5 × upper limit of normal (ULN) for age.
• AST and ALT ≤2.5 × ULN for age.
• Serum creatinine \<2 × ULN for age.
• Cardiac enzymes \<2 × ULN for age.
• Ejection fraction within normal range by echocardiogram (ECHO).
• Signed informed consent: By patient (≥18 years) or legal guardian/relative (\<18 years or if beneficial for condition).

You may not qualify if:

• Patients with diabetes receiving other medications
• Known allergy to metformin
• Deemed unsuitable by investigator

Sponsors & Collaborators

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

MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Central Study Contacts

Hui Wei, MD

CONTACT

13132507161; weihui@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2025
• First Posted: September 23, 2025
• Study Start: October 30, 2025
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2029
• Last Updated: September 23, 2025

Record last verified: 2025-09