Repurposing Metformin As a Leukemia-preventive Drug in CCUS and LR-MDS
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorKirsten Grønbæk
About this trial
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).
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
Any prior treatment with metformin
A diagnosis of diabetes mellitus
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
Trial design
Design model
Single group
Treatments tested in this trial
Metformin
Drug2000 mg/day metformin for 12 months (1000 mg b.i.d.) with a slow up-titration six weeks prior to full dose treatment.
Treatment groups
40 Participants
are divided into 1 treatment groupGroup A: MetforminExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety as assessed by the number of serious adverse events including any suspected unexpected serious adverse reactions
To assess safety of metformin treatment in this off-label indication by the type, grade, and number of adverse events and serious adverse events including any suspected unexpected serious adverse reactions in the patients.
Time frame
From inclusion to 12 months of study treatment2
Safety as assessed by median maximum tolerated dose in mg/day
To assess safety of metformin treatment in this off-label indication by median maximum tolerated dose and a description of any changes in individual medication doses.
Time frame
From inclusion to 12 months of study treatment3
Feasibility as assessed by rates of recruitment/refusal rates
To assess feasibility of the study protocol in terms of recruitment and refusal rates.
Time frame
From inclusion to 12 months of study treatment4
Feasibility as assessed by 12 months follow-up, i.e., study completion, rate
To assess feasibility of the study protocol in terms of rate of study completion. To assess safety of metformin treatment in this off-label indication by the type, grade, and number of adverse events and serious adverse events including any suspected unexpected serious adverse reactions in the patients; drop-out rates; and a description of any changes in individual medication doses including median maximum tolerated dose.
Time frame
From inclusion to 12 months of study treatmentSecondary outcomes
1
Interim efficacy: Mutational burden as assessed by change in variant allele frequency
Change in variant allele frequency (ΔVAF) by next generation sequencing (NGS)
Time frame
From inclusion to 12 months of study treatment2
Interim efficacy: Patient-reported outcome measures based on the EORTC QLQ-C30
Change in patient-reported outcome measures (PROM), based on the validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).
Time frame
From inclusion to 4 months of study treatment3
Interim efficacy: Patient-reported outcome measures based on the EORTC QLQ-C30
Change in patient-reported outcome measures (PROM), based on the validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).
Time frame
From inclusion to 12 months of study treatment4
Interim efficacy: Patient-reported outcome measures based on the SF-36
Change in patient-reported outcome measures (PROM), based on the validated Short Form 36 Health Survey Questionnaire (SF-36).
Time frame
From inclusion to 4 months of study treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Kirsten Grønbæk
Lead sponsor
Rigshospitalet, Denmark
Sponsor institution
Steno Diabetes Center Copenhagen
Collaborator
Zealand University Hospital
Collaborator
Van Andel Research Institute
Collaborator
Herlev Hospital
Collaborator
Technical University of Denmark
Collaborator
Region Hovedstadens Apotek
Collaborator
University of Copenhagen
Collaborator
Source ClinicalTrials.gov