Checkpoint Inhibitor-induced Liver Injury (ChILI)

University of Nottingham

Status: Enrolling

Conditions: Immune-Mediated Hepatitis

Treatments: Diagnostic Test: Obtaining biological samples

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT04476563

20034

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 160 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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:

1. 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

2. 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.

Exclusion criteria

• 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).

Trial design

160 participants in 2 patient groups

ChILI

Description:

Patients who are already on CPI therapy and have developed liver injury

Treatment:

Diagnostic Test: Obtaining biological samples

Control

Description:

Patients with cancer who are starting on checkpoint inhibitors

Treatment:

Diagnostic Test: Obtaining biological samples