Clinical trial · Interventional
Metformin Inhibits DNMT3A Clonal Hematopoiesis in Acute Leukemia
Metformin Inhibits DNMT3A Clonal Hematopoiesis in Acute Leukemia: A Single-Arm Clinical Study
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| DNMT3A Gene Mutation | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Metformin | Drug | Metformin | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Metformin Treatment Arm
- description
- 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.
- interventionNames
- Drug: Metformin
Primary outcomes (1)
- measure
- Rate of major molecular response based on the variant-allele frequency (VAF) of DNMT3A R882 mutation at 6-month follow-up
- timeFrame
- up to 6 months
- description
- 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).
Secondary outcomes (8)
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 14 Years
Show eligibility criteria text
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
References
Publications (0)
Data not yet available