Testing metformin to help prevent leukemia in people with early blood disorders

Trial details

Who runs it

Kirsten Grønbæk

Trial code

NCT04741945EU 2024-518436-37-01

Record updated

22 November 2024

Original description

This is a single-arm pilot study of the feasibility and safety of metformin in patients with clonal cytopenia of undetermined significance (CCUS) or lower-risk myelodysplastic neoplasms (LR-MDS).Read full original descriptionShow less

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

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

Inclusion: A diagnosis of:; LR-MDS according to the revised international prognostic scoring system (IPSS-R), i.e., very low- or low-risk disease (IPSS-R score ≤3) in addition to a bone marrow blast percentage <5 OR; CCUS defined as the presence of somatic mutation(s) or cytogenetic abnormality not diagnostic of MDS or any other malignancy in the context of persistent cytopenia (>6 months) with other common causes of cytopenia ruled out in the setting of bone marrow morphology that is not diagnostic of MDS or any other malignancy, and hematolytic conditions have been ruled out. Peripheral blood cytopenia is defined as hemoglobin (hgb) <11.3 g/dL (7 mmol/L) in women and hgb <12.9 g/dL (8 mmol/L) in men, platelet count <150 x 109/L, or neutrophil count <1.8 x 109/L; Menopause, if being a female, defined as females >45 years of age who have experienced amenorrhea for minimum 12 months, without any other obvious pathological or physiological cause; ≥18 years of age; Written informed consent; Willingness to comply with mandatory aspects of the protocol; Ability to swallow pills; Healthy individuals matched on age, sex, and BMI, if possible, to individual patient participants in WP1; Written informed consent; Willingness to comply with mandatory aspects of the protocol.

Exclusion: Any prior treatment with metformin; Therapeutic radiation, immunosuppressive therapy (with the exception of corticosteroids), or chemotherapy within the past year; Treatment with granulocyte colony-stimulating factor within the past 30 days; Prior therapy with hypomethylating agents (i.e., azacitidine, decitabine); Treatment with immunosuppressive drugs (with the exception of corticosteroids) or chemotherapy within the past year or antibiotics within the past 6 months; A diagnosis of diabetes mellitus; Other active malignancy within the past five years; A diagnosis of diabetes mellitus, rheumatological disorders, autoimmune diseases or other inflammatory disorders, celiac disease, inflammatory bowel disease, or other gastrointestinal disorders or symptoms; eGFR <45 mL/min; Uncontrolled comorbidity including impaired hepatic function (total serum bilirubin >1.5 × upper limit of the normal range (ULN), serum alanine transaminase >3 × ULN), chronic hepatitis with decompensated cirrhosis, disabling psychiatric disease, severe neurologic disease, uncontrolled metabolic disease, or severe cardiac disease (NYHA class 3-4); An eGFR calculation performed up to one month prior to inclusion may be used to assess renal function. If such an assessment is not available, it is performed at screening; Healthy volunteers are eligible to be included in WP0 if they meet all of the following criteria:; Performance status according to the Eastern Cooperative Oncology Group >2; Use of metformin within the past 3 years; Any contraindications to MRS.

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

ClinicalTrials.gov NCT04741945 · EU CTIS 2024-518436-37-01