STOP-LEUKEMIA: Repurposing Metformin As a Leukemia-preventive Drug in CCUS and LR-MDS
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Safety as assessed by the number of serious adverse events including any suspected unexpected serious adverse reactions
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Metformin
2000 mg/day metformin for 12 months.
干预措施: Metformin (Drug)
结局指标
主要结局
Safety as assessed by the number of serious adverse events including any suspected unexpected serious adverse reactions
时间窗: From inclusion to 12 months of study treatment
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.
Safety as assessed by median maximum tolerated dose in mg/day
时间窗: From inclusion to 12 months of study treatment
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.
Feasibility as assessed by rates of recruitment/refusal rates
时间窗: From inclusion to 12 months of study treatment
To assess feasibility of the study protocol in terms of recruitment and refusal rates.
Feasibility as assessed by 12 months follow-up, i.e., study completion, rate
时间窗: From inclusion to 12 months of study treatment
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.
Feasibility as assessed by rate of compliance to protocol procedures
时间窗: From inclusion to 12 months of study treatment
To assess feasibility of the study protocol in terms of rate of adherence to protocol procedures (study medication and study procedures).
次要结局
- Interim efficacy: Patient-reported outcome measures based on the SF-36(From inclusion to 12 months of study treatment)
- Interim efficacy: Mutational burden as assessed by change in variant allele frequency(From inclusion to 12 months of study treatment)
- Interim efficacy: Patient-reported outcome measures based on the EORTC QLQ-C30(From inclusion to 12 months of study treatment)
- Interim efficacy: Patient-reported outcome measures based on the EQ-5D(From inclusion to 12 months of study treatment)
- Interim efficacy: Bone marrow adipose tissue as assessed by MR spectroscopy ratio of adipose tissue and water phase(From inclusion to 12 months of study treatment)
- Interim efficacy: Gut microbiota composition as assessed by 16S rRNA sequencing(From inclusion to 12 months of study treatment)
- Interim efficacy: Epigenetic regulation as assessed by levels of 5-mC and 5-hmC(From inclusion to 12 months of study treatment)
- Interim efficacy: Gene expression as assessed by RNA sequencing(From inclusion to 12 months of study treatment)
- Interim efficacy: Protein profiles as assessed by proteomics(From inclusion to 12 months of study treatment)
- Interim efficacy: Bone mineral density as assessed by DEXA scan measured in grams per cubic centimeter with resulting Z score(From inclusion to 12 months of study treatment)
- Interim efficacy: Body composition as assessed by DEXA scan presented as whole body bone mass and soft tissue composition(From inclusion to 12 months of study treatment)
- Interim efficacy: Small intestinal permeability as assessed by urine-lactulose/mannitol measurement and ion chromatography(From inclusion to 4 months of study treatment)
- Interim efficacy: Response and disease progression as according to the IWG response criteria in myelodysplastic neoplasms(From inclusion to 12 months of study treatment)
- Interim efficacy: Bone marrow niche factor levels as assessed by ELISA(From inclusion to 12 months of study treatment)
- Interim efficacy: Cytokine levels as assessed by ELISA(From inclusion to 12 months of study treatment)
研究者
Kirsten Grønbæk
Professor, MD, DMSc
Rigshospitalet, Denmark