Multicenter Study Using IMC to Analyze the Impact of ICANS on Microglia

• Sponsor: University of Freiburg (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05811117
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Anticipated Duration (Months): 23.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Immunotherapy with chimeric antigen receptor (CAR) T cell therapy can cause immune effector cell-associated neurotoxicity syndrome (ICANS). However, the molecular mechanisms leading to ICANS are not well understood. In this study, the investigators plan to examine the role of microglia as the primary parenchymal immune cells of the central nervous system (CNS) during ICANS in human samples. The samples will be analyzed using imaging-mass-cytometry-based analysis (IMC). Single-cell data will be obtained through machine learning supervised segmentation of IMC data. Single-cell marker expression in all cells and in microglia (Iba1+ cells) will be analyzed in patients with ICANS.

Condition or Disease	Intervention/Treatment	Phase
ICANS, Grade Unspecified; CAR T-Cell-Related Encephalopathy Syndrome	Diagnostic Test: There will be no intervention as we will study patients that undergo autopsy after CAR T cell infusion.

Detailed Description

Immunotherapy with chimeric antigen receptor (CAR) T cell therapy can cause immune effector cell-associated neurotoxicity syndrome (ICANS).

Previous studies have shown a role for IL-1beta and IL-6 in xenograft mouse models.

However, the molecular mechanisms leading to ICANS are not well understood. In this study, the investigators plan to examine the role of microglia as the primary parenchymal immune cells of the central nervous system (CNS) during ICANS in human samples. The samples will be analyzed using imaging-mass-cytometry-based analysis (IMC). Single-cell data will be obtained through machine learning supervised segmentation of IMC data. Single-cell marker expression in all cells and in microglia (Iba1+ cells) will be analyzed in patients with ICANS. The participants are patients treated with chimeric antigen receptor (CAR) T cell therapy. The patients will received TSPO-PET imaging if available and if an autopsy is performed underroutine conditions tissue is collected for IMC based analysis.

Study Design

• Study Type: Observational
• Anticipated Enrollment: 8 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Multicenter Study Using Imaging Mass Cytometry to Analyze the Impact of ICANS on Microglia
• Actual Study Start Date: Apr 12, 2021
• Anticipated Primary Completion Date: Apr 5, 2023
• Anticipated Study Completion Date: Apr 5, 2023

Outcome Measures

Primary Outcome Measures

1. HLA-DRA and HLA-DR on Iba1+ cells [2 years]

   We will study HLA-DRA and HLA-DR on Iba1+ cells

2. Clusters of activated microglia and macrophages will be studied in patients with ICANS [2 years]

   Clusters of activated microglia and macrophages will be studied in patients with ICANS

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients that had developed ICANS

• CAR T cell infusion for lymphoid malignancy (NHL or ALL)

Exclusion Criteria:

• Lack of consent of patient or legal guardian

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Freiburg University Medical Center	Freiburg	Baden Württemberg	Germany	79106

Sponsors and Collaborators

• University of Freiburg

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Zeiser, Director Division of Tumor Immunology, University of Freiburg
• ClinicalTrials.gov Identifier: NCT05811117
• Other Study ID Numbers: UKLFR02022021
• First Posted: Apr 13, 2023
• Last Update Posted: Apr 18, 2023
• Last Verified: Apr 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Brain Diseases

Study Results

No Results Posted as of Apr 18, 2023