Checkpoint Inhibitor-induced Liver Injury Study (ChILI)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Incidence of checkpoint inhibitor-induced liver injury (ChILI) and other immune-mediated adverse reactions
研究概览
简要总结
In this multi-center prospective observational study, the investigators plan to identify the incidence and risk factors for checkpoint inhibitor-induced liver injury and characterize biochemical, genetic, immunological, and histological features associated with it.
详细描述
Checkpoint inhibitor-induced liver injury (ChILI) is a new incompletely understood category of hepatotoxicity which is distinct from other types of drug-induced liver injury (DILI) such as direct or idiosyncratic DILI. The data regarding the incidence and risk factors is lacking. Therefore, 'in-depth phenotyping' together with data from the control group exposed to checkpoint inhibitors (CPI) is necessary to develop refined algorithms incorporating CPI-related factors, host genetic and environmental risk factors that would enable pre-empting ChILI.
The aim of the study is to enroll two deeply phenotyped cohorts (patients who developed ChILI and patients who are starting checkpoint inhibitors) and obtain biological samples at multiple time points.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Both patient groups and control group:
- •Able to give written informed consent OR Potential participants who have developed encephalopathy related to ChILI as a response to checkpoint inhibitor therapy, who lack the capacity to give written informed consent and have a consultee (personal or nominated) - for ChILI patient group only
- •ChILI group:
- •Patients who developed checkpoint inhibitor-induced liver injury and meet the following criteria:
- •Meets one of the following analytical thresholds at enrolment (visit 1)
- •Alanine transaminase (ALT) exceeding 5 times the upper limit of normal (ULN) OR
- •ALT exceeding 3 times ULN plus bilirubin exceeding 2 times ULN OR
- •Alkaline phosphatase (ALP) exceeding 2 times ULN with accompanying elevations of gamma-glutamyl transferase in the absence of known bone metastases driving the rise in ALP level
- •Absence of other known causes of liver injury after detailed investigations
- •Patients who developed ChILI but did not meet the above criteria at enrolment or who were found to have a different cause for their liver injury after further investigations will be excluded from the analysis
- •Control group:
- •Consecutive patients with cancer who have a clinical indication to start checkpoint inhibitors. A small proportion of patients will develop ChILI following their checkpoint inhibitor treatment and will be classified as cases.
排除标准
- •Patients who are treated with cytotoxic chemotherapy concurrently with checkpoint inhibitors.
- •On the judgment of chief investigator that the person has certain alternative explanations to the acute event (rather than ChILI).
结局指标
主要结局
Incidence of checkpoint inhibitor-induced liver injury (ChILI) and other immune-mediated adverse reactions
时间窗: 3 years
Identify novel biomarkers associated with the diagnosis of ChILI
时间窗: 3 years
The investigators plan assessment of proposed circulating biomarkers including cytokines, microRNAs (miR-122, miR-4270 and miR-4463), total cytokeratin 18 (K18), macrophage colony-stimulating factor receptor (MCSFR), and any others identified in subsequent publications and measure their diagnostic and prognostic accuracy using the area under the receiver operating curve (AUROC).
次要结局
未报告次要终点