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

• Status: Not yet recruiting
• Trial end date: 2025-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase 2 single-arm pilot study of the efficacy and safety of metformin in patients with clonal cytopenia of undetermined significance (CCUS) or lower-risk myelodysplastic syndrome (MDS).

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Kirsten Grønbæk
• Collaborators: Herlev Hospital; Region Hovedstadens Apotek; Rigshospitalet, Denmark; Steno Diabetes Center Copenhagen; Technical University of Denmark; University of Copenhagen; Van Andel Research Institute; Zealand University Hospital
• Treatments: Metformin

Criteria

Patients are eligible to be included in WP1, if they meet all the following criteria:

• Have a diagnosis of either:

1. LR-MDS according to revised international prognostic scoring system (IPSS-R), i.e.

very low-risk to intermediate (IPSS-R score ≤ 3).

2. CCUS defined as the presence of somatic mutations and persistent cytopenia for more than six months with other common causes of cytopenia been ruled out. Peripheral blood (cytopenias are defined as thrombocytes below 150×10^9 cells/L, neutrophils below 1.8×10^9 cells/L, and hemoglobin below 12.9 g/dL (8 mmol/L) in men and 11.3 g/dL (7 mmol/L) in women.

• Menopausal, if being a female, defined as females >45 years of age who has experienced amenorrhea for minimum 12 months, without any other obvious pathological or physiological cause.

• ≥18 years of age.

• Have given written informed consent prior to any study-specific procedures.

• Are able to swallow capsules.

Patients will be excluded from the study/WP1, if they meet any of the following criteria:

• Ongoing therapy with metformin or other diabetic pharmaceuticals e.g. insulin.

• History of not tolerating metformin.

• Therapeutic radiation or chemotherapy within the past six months.

• Prior therapy with hypomethylating agents (e.g. azacytidine, decitabine).

• eGFR < 45 mL/min.

• Unwillingness to comply with the mandatory aspects of the protocol.

Inclusion criteria for WP0 (healthy volunteers):

• above 60 years of age.

• have given a written informed consent prior to study procedures.

• willing to have an MRS.

Exclusion criteria for WP0 (Healthy volunteers):

• Any contraindications to MRS