Actively Recruiting

Phase 2
Age: 18Years +
All Genders
Healthy Volunteers
ID04741945

STOP-LEUKEMIA: Repurposing Metformin As a Leukemia-preventive Drug in CCUS and LR-MDS

Led by Kirsten Grønbæk · Updated on 2024-11-22

40

Participants Needed

1

Research Sites

N/A

Total Duration

On this page

Sponsors

K

Kirsten Grønbæk

Lead Sponsor

S

Steno Diabetes Center Copenhagen

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are evaluating the safety and feasibility of using metformin in patients with clonal cytopenia of undetermined significance (CCUS) or lower-risk myelodysplastic neoplasms (LR-MDS), conditions that may progress to leukemia. This phase 2 pilot study explores biological features such as bone marrow fat tissue, gut microbiota, and intestinal permeability that may play a role in disease progression and could be targets for metformin treatment. The study also compares findings to healthy elderly controls for better understanding. Participants in the main treatment group will receive up to 2000 mg of metformin daily for 12 months, with a slow increase to the full dose over six weeks. The study is divided into three parts: the first investigates biological markers in both patients and healthy volunteers; the second assesses metformin safety, adherence, and possible anti-leukemic mechanisms in patients; and the third compares safety and early efficacy of metformin to historical placebo controls from a previous randomized study. During the 12 months of treatment, participants will be monitored for safety by tracking serious side effects and the highest tolerated dose. Feasibility will be assessed through recruitment, completion, and compliance rates. Researchers will also measure changes in genetic mutations, patient-reported health outcomes, bone marrow fat, bone density, gut bacteria, intestinal permeability, gene expression, protein profiles, and immune markers. The involvement includes various scans, blood and bone marrow tests, and questionnaires, with the total participation lasting approximately one year.

CONDITIONS

Brief Title

Repurposing Metformin As a Leukemia-preventive Drug in CCUS and LR-MDS

Who Can Participate

Age: 18Years +
All Genders
Healthy Volunteers

Eligibility Criteria

Eligible

You may qualify if you...

  • Diagnosis of lower-risk myelodysplastic neoplasm (LR-MDS) with IPSS-R score 3 and bone marrow blasts <5%, or diagnosis of clonal cytopenia of undetermined significance (CCUS) with persistent cytopenia >6 months and no other causes
  • Female participants must be menopausal, defined as over 45 years old with at least 12 months of amenorrhea
  • Age 18 years or older
  • Written informed consent provided
  • Willingness to follow mandatory study procedures
  • Ability to swallow pills
Not Eligible

You will not qualify if you...

  • Prior treatment with metformin
  • Diagnosis of diabetes mellitus
  • Therapeutic radiation, immunosuppressive therapy (except corticosteroids), or chemotherapy within the past year
  • Treatment with granulocyte colony-stimulating factor within the past 30 days
  • Prior therapy with hypomethylating agents such as azacitidine or decitabine
  • Estimated glomerular filtration rate (eGFR) less than 45 mL/min
  • Eastern Cooperative Oncology Group performance status greater than 2
  • Other active malignancy within the past five years
  • Uncontrolled comorbidities including impaired liver function, chronic hepatitis with decompensated cirrhosis, severe psychiatric or neurologic disease, uncontrolled metabolic disease, or severe heart disease (NYHA class 3-4)

AI-Screening

AI-Powered Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

Run-in Period

Duration - 6 weeks

Participants undergo a slow up-titration of metformin to reach the maximum tolerated dose before full dose treatment.

Treatment

Duration - 12 months

Participants receive metformin 2000 mg daily or their maximum tolerated dose for 12 months to evaluate safety, feasibility, and potential mechanisms of action.

Regular visits for study assessments during treatment

Trial Site Locations

Total: 1 location

1

Rigshospitalet

Copenhagen, Copenhagen N, Denmark, 2200

Actively Recruiting

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Research Team

K

Kirsten Grønbæk, Professor, MD

S

Stine Ulrik Mikkelsen, MD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

OTHER

Number of Arms

1

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