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

Status Recruiting

Clinical Trial Summary

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).

Clinical Trial Description

The research plan is divided into three work packages (WP): WP0: Bone Marrow Adipose Tissue, Gut Microbiota, and Intestinal Permeability in CCUS and LR-MDS Patients. The aim of WP0 is to investigate biological features which the investigators hypothesize to be of pathogenetic relevance for MDS progression and may be possible targets of metformin treatment. For this purpose, 20 elderly (≥60 years) healthy controls will be included for comparison to patients with CCUS or LR-MDS from WP1. The primary objectives are to investigate 1) the abundance and properties of bone marrow adipose tissue (BMAT) and bone marrow (BM) adipocytes, and 2) the gut microbiota and intestinal permeability of patients with CCUS or LR-MDS compared to age-, sex- and body mass index (BMI)-matched healthy controls. Secondary objectives are to characterize DNA methylation and hydroxymethylation (5-mC and 5-hmC) patterns, and hormone and cytokine levels in BM plasma from healthy controls and patients with CCUS or LR-MDS. WP1: Safety, feasibility, and mechanisms of action of metformin in patients with CCUS or LR-MDS. In this WP up to 40 patients with CCUS or LR-MDS will receive metformin 2000 mg daily or their maximum tolerated dose (MTD) for 12 months. The aim of WP1 is to investigate safety of metformin and feasibility of the protocol in patients with CCUS or LR-MDS. Potential mechanisms of anti-leukemic action of metformin will also be explored in order to identify a suitable outcome measure and estimate standard deviation of the outcome measure. All in order to inform the design of a future phase 3 RCT of the efficacy of metformin in CCUS and LR-MDS patients. Endpoints of WP1 are specified in the corresponding section. WP2: Safety and efficacy of metformin compared to placebo. The primary objective of WP2 is to compare safety and preliminary efficacy of metformin in patients with CCUS or LR-MDS to a cohort of patients with CCUS or LR-MDS receiving placebo in context of our EVI-2 randomized, controlled pilot study (NCT03999723). Data and samples from approximately 50 historical controls will be included from the EVI-2 study in which participants were randomized to receive placebo or oral vitamin C supplement for 12 months. ;

Study Design

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT04741945
Study type	Interventional
Source	Rigshospitalet, Denmark
Contact	Kirsten Grønbæk, Professor, MD
Phone	+45 35456060
Email	Kirsten.Groenbaek@regionh.dk
Status	Recruiting
Phase	Phase 2
Start date	December 13, 2021
Completion date	June 2026

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Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

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

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms