DNMT3A Gene MutationPhase 1NCT07188740
Metformin Inhibits DNMT3A Clonal Hematopoiesis in Acute Leukemia
A Phase 1 study testing Metformin in people with DNMT3A Gene Mutation, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- DNMT3A Gene Mutation
- What is being tested?
- Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteChina
- Study dates
- 30 Aug 2026to 30 Aug 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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).
Who cannot join
- Patients with diabetes receiving other medications
- Known allergy to metformin
- Deemed unsuitable by investigator
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Blood Diseases Hospital
Tianjin, Tianjin Municipality, 300020
Hui Wei, MD
About this study
Official title: Metformin Inhibits DNMT3A Clonal Hematopoiesis in Acute Leukemia: A Single-Arm Clinical Study
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.
Read the detailed description
Clonal hematopoiesis (CHIP) involves hematopoietic stem cells (HSCs) acquiring mutations like DNMT3A R882, conferring a proliferative advantage and increasing risks of hematologic malignancies and inflammatory diseases. No effective interventions exist currently. Preclinical studies show that DNMT3A R882 mutations enhance mitochondrial respiration and oxidative phosphorylation (OXPHOS) in hematopoietic stem/progenitor cells (HSPCs), which is essential for their competitive advantage. Metformin, at clinical doses, inhibits the electron transport chain (ETC) complex I, reducing OXPHOS and selectively diminishing the advantage of mutant HSPCs. Mechanisms include restoring epigenetic stability by elevating methylation potential (SAM/SAH ratio), reversing hypomethylation in differential methylation regions (DMRs), and normalizing H3K27me3 histone modifications.
In mouse and humanized models, metformin suppresses clonal expansion of DNMT3A R882 mutant cells. Based on metformin's 60-year safety profile in diabetes treatment, this study tests its potential in AL patients with persistent DNMT3A R882 CH post-remission. Metformin may reduce risks like secondary tumors and diabetes in these patients.
Study intervention: Oral metformin starting at 500 mg twice daily, titrated to 500 mg three times daily or 1000 mg twice daily (or maximum tolerated dose), up to 2000 mg/day, taken with meals for 6 months.
Efficacy assessment: Next-generation sequencing (NGS) for DNMT3A R882 VAF at 0, 3, and 6 months.
- Major response: For VAF >20%, absolute decline ≥10%; for VAF ≤20%, relative decline ≥50%.
- Partial response: For VAF >20%, absolute decline 5-10%; for VAF ≤20%, relative decline 25-50%.
Safety monitoring: Close monitoring of liver/kidney function, especially in patients ≥60 years or with renal impairment, due to lactic acidosis risk.
Data management uses electronic case report forms (eCRF). Statistical analysis includes intention-to-treat (ITT) and per-protocol (PP) sets, with Kaplan-Meier for survival, t-tests, Wilcoxon rank-sum, chi-square, and Cox proportional hazards models.
- Conditions
- DNMT3A Gene Mutation
- Being tested
- Metformin
- Keywords
- CHIP, acute leukemia, Metformin, DNMT3A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Start at 500 mg twice daily, titrate to 2000 mg/day for 6 months
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of major molecular response based on the variant-allele frequency (VAF) of DNMT3A R882 mutation at 6-month follow-up
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).
Measured: up to 6 months
Secondary outcomes (8)
Rate of major molecular response based on the variant-allele frequency (VAF) of DNMT3A R882 mutation at 3-month follow-up
The judgment standard for major molecular-response is consistent with the primary endpoint.
VAF is detected in bone-marrow samples via next-generation sequencing (NGS).
Measured: up to 3 months
Relapse-Free Survival (RFS) Rate at 6 Months
Measured: up to 6 months
Relapse-Free Survival (RFS) Rate at 12 Months
Proportion of patients without relapse
Measured: up to 12 months
Overall Survival (OS) Rate
Proportion of patients alive
Measured: Up to 12 months
Cumulative Incidence of Relapse (CIR)
Cumulative rate of relapse events
Measured: Up to 12 months
Cumulative Remission-Phase Mortality Rate
Cumulative rate of deaths during remission
Measured: Up to 12 months
Rate of Overall Response of DNMT3A R882 Mutation VAF at 3 Months
Measured: up to 3 months
Rate of Overall Response of DNMT3A R882 Mutation VAF at 6 Months
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2025
- Study start30 Aug 2026 (estimated)
- Primary completion30 Aug 2027 (estimated)
- Study completion30 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DNMT3A Gene MutationStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07188740
- Sponsor's protocol ID
- IIT2025104
- Status last verified
- Aug 2026
- First submitted
- 16 Sep 2025
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin Inhibits DNMT3A Clonal Hematopoiesis in Acute Leukemia: A Single-Arm Clinical Study
- ClinicalTrials.gov ID
- NCT07188740
- Acronym / sponsor ID
- IIT2025104
- Conditions
- DNMT3A Gene Mutation
- Keywords
- CHIP, acute leukemia, Metformin, DNMT3A
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Study start
- 30 Aug 2026 (estimated)
- Primary completion
- 30 Aug 2027 (estimated)
- Study completion
- 30 Aug 2029 (estimated)
- First posted
- 23 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Clonal hematopoiesis (CHIP) involves hematopoietic stem cells (HSCs) acquiring mutations like DNMT3A R882, conferring a proliferative advantage and increasing risks of hematologic malignancies and inflammatory diseases. No effective interventions exist currently. Preclinical studies show that DNMT3A R882 mutations enhance mitochondrial respiration and oxidative phosphorylation (OXPHOS) in hematopoietic stem/progenitor cells (HSPCs), which is essential for their competitive advantage. Metformin, at clinical doses, inhibits the electron transport chain (ETC) complex I, reducing OXPHOS and selectively diminishing the advantage of mutant HSPCs. Mechanisms include restoring epigenetic stability by elevating methylation potential (SAM/SAH ratio), reversing hypomethylation in differential methylation regions (DMRs), and normalizing H3K27me3 histone modifications.
In mouse and humanized models, metformin suppresses clonal expansion of DNMT3A R882 mutant cells. Based on metformin's 60-year safety profile in diabetes treatment, this study tests its potential in AL patients with persistent DNMT3A R882 CH post-remission. Metformin may reduce risks like secondary tumors and diabetes in these patients.
Study intervention: Oral metformin starting at 500 mg twice daily, titrated to 500 mg three times daily or 1000 mg twice daily (or maximum tolerated dose), up to 2000 mg/day, taken with meals for 6 months.
Efficacy assessment: Next-generation sequencing (NGS) for DNMT3A R882 VAF at 0, 3, and 6 months.
- Major response: For VAF >20%, absolute decline ≥10%; for VAF ≤20%, relative decline ≥50%.
- Partial response: For VAF >20%, absolute decline 5-10%; for VAF ≤20%, relative decline 25-50%.
Safety monitoring: Close monitoring of liver/kidney function, especially in patients ≥60 years or with renal impairment, due to lactic acidosis risk.
Data management uses electronic case report forms (eCRF). Statistical analysis includes intention-to-treat (ITT) and per-protocol (PP) sets, with Kaplan-Meier for survival, t-tests, Wilcoxon rank-sum, chi-square, and Cox proportional hazards models.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metformin Treatment Arm | Experimental | Drug: MetforminDosage: 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. |
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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):
- Signed informed consent: By patient (≥18 years) or legal guardian/relative (<18 years or if beneficial for condition).
Key exclusion criteria (3 listed)
- Patients with diabetes receiving other medications
- Known allergy to metformin
- Deemed unsuitable by investigator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminStart at 500 mg twice daily, titrate to 2000 mg/day for 6 months | Drug | Metformin Treatment Arm |
Primary outcome
Rate of major molecular response based on the variant-allele frequency (VAF) of DNMT3A R882 mutation at 6-month follow-up
Time frame: 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).
8 secondary outcomes
Rate of major molecular response based on the variant-allele frequency (VAF) of DNMT3A R882 mutation at 3-month follow-up
Time frame: up to 3 months
Relapse-Free Survival (RFS) Rate at 6 Months
Time frame: up to 6 months
Relapse-Free Survival (RFS) Rate at 12 Months
Time frame: up to 12 months
Overall Survival (OS) Rate
Time frame: Up to 12 months
Cumulative Incidence of Relapse (CIR)
Time frame: Up to 12 months
Cumulative Remission-Phase Mortality Rate
Time frame: Up to 12 months
Rate of Overall Response of DNMT3A R882 Mutation VAF at 3 Months
Time frame: up to 3 months
Rate of Overall Response of DNMT3A R882 Mutation VAF at 6 Months
Time frame: up to 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metformin in people with DNMT3A Gene Mutation, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hui Wei, MD (13132507161, weihui@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of major molecular response based on the variant-allele frequency (VAF) of DNMT3A R882 mutation at 6-month follow-up (time frame: up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.