Institute of Hematology & Blood Diseases Hospital, China
Phase
Phase 1
Started
2026-08-30
Last updated
2026-08-10
Condition(s) studied
DNMT3A Gene Mutation
Investigational drug(s) / intervention(s)
Metformin
Metformin: Start at 500 mg twice daily, titrate to 2000 mg/day for 6 months
Study 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: 32 participants.
Eligibility
Sex
ALL
Min age
14 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* 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).
Exclusion Criteria:
* Patients with diabetes receiving other medications
* Known allergy to metformin
* Deemed unsuitable by investigator
Primary outcome measure(s)
Rate of major molecular response based on the variant-allele frequency (VAF) of DNMT3A R882 mutation at 6-month follow-up — up to 6 months An effective decline in VAF is defined as an absolute reduction of ≥10% when the baseline variant-allele frequency is greater than 20%; a relative reduction of ≥50% when the baseline variant-allele frequency is ≤20%.
Variant-allele frequency is tested in bone-marrow samples via next-generation sequencing (NGS).
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.