NFL-ICI: Investigational Biomarkers for Neurological Immune-related Adverse Events

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Recruiting

CT.gov ID

NCT05969379

Collaborator

(none)

Enrollment

Location

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Neurological immune-related adverse events (n-irAEs) are an emerging group of disorders of patients with cancer treated with immune checkpoint inhibitors, presenting with heterogeneous clinical manifestations and of uncertain outcome. Novel genetic, inflammatory, and neurogenerative biomarkers could be associated with distinct phenotypes and different outcomes. To test this hypothesis, the study will provide: a phenotypic characterization and outcome assessment of patients with n-irAEs; the analysis of biomarkers of genetic predisposition (HLA and other immunity-related genes), inflammation (serum and cerebrospinal fluid [CSF] cytokines and autoantibodies, peripheral blood and CSF lymphocytes and other immune cells, neuroimaging), neurodegeneration (serum and CSF neurofilaments, neuroimaging) and their correlation with clinical features and outcome.

Condition or Disease	Intervention/Treatment	Phase
Neurological Disease	Genetic: Analysis of biomarkers and their correlation with clinical characteristics and outcome

Study Design

Study Type:

Observational

Anticipated Enrollment :

80 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

Genetic Predisposition, Inflammation, and Neurodegeneration Biomarkers in Patients With Neurological Adverse Events of Immune Checkpoint Inhibitors: Correlation With Clinical Phenotypes and Outcome

Actual Study Start Date :

May 1, 2022

Actual Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Patients with neurological immune-related adverse events (n-irAEs) Patients developing neurological syndromes related to administration of any immune checkpoint inhibitors, including central nervous system disorders and neuromuscular toxicties	Genetic: Analysis of biomarkers and their correlation with clinical characteristics and outcome This is a non-interventional study involving clinical data, neuroimaging analysis, and biological samples. Demographics and clinical data are collected in the database of the French Reference Centre. Additional or missing data will be obtained by contacting the referral physicians. All the neuroimages available will be analysed by dedicated software. Samples are already stored in biobank repositories and collected as part of "good clinical practice" in the diagnostic process of patients with suspected autoimmune encephalitis, meaning that the standard diagnostic and therapeutic approaches will not be altered in the selected study population. Patients have already gave explicit written consent for biological specimens sampling and storage at the "Centre de Ressources Biologiques des Hospices Civils de Lyon" (CRB-HCL) (including tissue, cells or biological fluids). Additional samples for genetic testing will be collected upon explicit written consent.

Arm

Intervention/Treatment

Patients with neurological immune-related adverse events (n-irAEs)

Patients developing neurological syndromes related to administration of any immune checkpoint inhibitors, including central nervous system disorders and neuromuscular toxicties

Genetic: Analysis of biomarkers and their correlation with clinical characteristics and outcome

This is a non-interventional study involving clinical data, neuroimaging analysis, and biological samples. Demographics and clinical data are collected in the database of the French Reference Centre. Additional or missing data will be obtained by contacting the referral physicians. All the neuroimages available will be analysed by dedicated software. Samples are already stored in biobank repositories and collected as part of "good clinical practice" in the diagnostic process of patients with suspected autoimmune encephalitis, meaning that the standard diagnostic and therapeutic approaches will not be altered in the selected study population. Patients have already gave explicit written consent for biological specimens sampling and storage at the "Centre de Ressources Biologiques des Hospices Civils de Lyon" (CRB-HCL) (including tissue, cells or biological fluids). Additional samples for genetic testing will be collected upon explicit written consent.

Outcome Measures

Primary Outcome Measures

Analysis of neurofilaments [At enrollment]
Neurofilaments will be analysed by MSD. Meso Scale Discovery Electrochemiluminescence (MSD) uses sandwich enzyme-linked immunosorbent assay (ELISA) method coupled with electro¬chemiluminescence (ECL) detection and plate array technology to provide highly sensitive and multiplexed detection of the analytes of interest (like neurofilaments) in a complex biological matrix.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Clinical diagnosis of n-irAEs

Exclusion Criteria:

Presence of an alternative diagnosis explaining the neurological syndrome

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre de référence des syndromes neurologiques paranéoplasiques et encéphalites auto-immunes, Hôpital neurologique Pierre Wertheimer	Bron		France	69500