NCT07456358

Brief Summary

The pathophysiology of neurological toxicities secondary to immune checkpoint inhibitors (ICIs) is unknown. Various mechanisms have been proposed: activation of cytotoxic CD8 T cells, autoantibodies via activation of B cells and CD4 cells, non-specific inflammation through the production of pro-inflammatory cytokines, and complement activation. The aim of this research is to characterise the pathophysiological mechanisms of neurotoxicities in cancer patients treated with ICIs.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
160

participants targeted

Target at P75+ for not_applicable

Timeline
55mo left

Started Mar 2026

Longer than P75 for not_applicable

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress4%
Mar 2026Nov 2030

First Submitted

Initial submission to the registry

February 11, 2026

Completed
18 days until next milestone

Study Start

First participant enrolled

March 1, 2026

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 6, 2026

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2030

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2030

Last Updated

March 6, 2026

Status Verified

March 1, 2026

Enrollment Period

4.7 years

First QC Date

February 11, 2026

Last Update Submit

March 4, 2026

Conditions

Keywords

Autoimmune neurological diseasesImmunotherapyNeurotoxocitiesImmune checkpoint inhibitors

Outcome Measures

Primary Outcomes (1)

  • Presence of nervous system-specific TCRs in CSF of patients with ICI-related neurotoxicity

    Specific TCR repertoires of ICI-related neurotoxicity will be identified by TCR sequencing of CSF and blood lymphocytes of patients at the time of diagnosis of neurotoxicity of ICIs in comparison to those found in the control cohort 1.2. The target of these lymphocytes specifically found in cohort 1.1 will be assessed by EliSpot with known neuronal antigens as well as a search for serum and CSF onconeuronal autoantibodies. In silico methods as well as public TCR database will also be used to find the neurological targets.

    At day 1

Secondary Outcomes (3)

  • Proportions of lymphocytes

    At day 1

  • Concentration of pro and anti-inflammatory cytokines in CSF of patients with ICI-related neurotoxicity and control cohorts

    At day 1

  • Presence and strength of correlation between TCR repertoires and phenotype/ expression profile of CSF lymphocytes and clinical presentation of ICI-related neurotoxicity

    At day 1

Study Arms (4)

Study group : cancer patients developing neurological symptoms after starting treatment with immune

EXPERIMENTAL
Other: Lumbar puncture and blood sampling

Control group : cancer patients undergoing treatment with ICIs and experiencing neurological symptom

EXPERIMENTAL
Other: Lumbar puncture and blood sampling

Control group : patients with an autoimmune disease of the central nervous system

EXPERIMENTAL
Other: Lumbar puncture and blood sampling

Control group : patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hyperte

EXPERIMENTAL
Other: Lumbar puncture and blood sampling

Interventions

For all patients in the study, lumbar puncture will be performed as part of their care, according to the clinical indication given by the referring physician. If the patient gives their consent, an additional volume of CSF will be collected for this study, so that the total volume collected (care plus research) does not exceed 5 mL. No lumbar puncture will be performed specifically for the study. Blood samples will also be collected: these are additional blood tubes collected during a blood sample taken as part of the treatment (as described in the section 'Minimal risks and constraints added by the research').

Control group : cancer patients undergoing treatment with ICIs and experiencing neurological symptomControl group : patients with an autoimmune disease of the central nervous systemControl group : patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hyperteStudy group : cancer patients developing neurological symptoms after starting treatment with immune

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adult patient (aged ≥ 18 years)
  • Affiliated with a social security scheme
  • Express consent to participate in the study
  • Indication for lumbar puncture And
  • Patients with cancer, undergoing treatment with ICIs, presenting neurological symptoms after starting treatment with ICIs. These symptoms must have appeared no more than 3 months after the last administration of ICIs.
  • Patients with an autoimmune disease of the central nervous system (diagnosis made by teams 1, 2 and 3) according to internationally recognised criteria, with no history of active cancer in the last 3 years and no other autoimmune disease Or
  • Patients with normal pressure hydrocephalus (NPH) or idiopathic intracranial hypertension (diagnosed based on imaging (brain MRI) and clinical findings), with no history of active cancer in the last 3 years and no active autoimmune disease

You may not qualify if:

  • Contraindication or refusal to perform a lumbar puncture
  • Sample not suitable for research (volume of CSF collected for treatment \>5 mL)
  • Pregnant or breastfeeding women
  • Not affiliated with the social security system, patients under French State Medical Aid for undocumented migrants
  • Patients under guardianship or curatorship, under judicial protection measures, or deprived of their liberty by judicial or administrative decision

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Interventions

Spinal PunctureBlood Specimen Collection

Intervention Hierarchy (Ancestors)

BiopsySpecimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisDiagnostic Techniques, NeurologicalPuncturesTherapeuticsSurgical Procedures, OperativeInvestigative Techniques

Central Study Contacts

Stefania Cuzzubbo, MD

CONTACT

Jérôme Lambert, MD PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 11, 2026

First Posted

March 6, 2026

Study Start

March 1, 2026

Primary Completion (Estimated)

November 1, 2030

Study Completion (Estimated)

November 1, 2030

Last Updated

March 6, 2026

Record last verified: 2026-03