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

Multicenter Study Using Imaging Mass Cytometry to Analyze the Impact of ICANS on Microglia

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.

Study Overview

• Status: Completed
• Conditions: CAR T-Cell-Related Encephalopathy Syndrome; ICANS, Grade Unspecified
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• Germany
  • Baden Württemberg
    • Freiburg, Baden Württemberg, Germany, 79106
      • Freiburg University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients that had developed ICANS after CAR T cell infusion will be analyzed.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HLA-DRA and HLA-DR on Iba1+ cells	We will study HLA-DRA and HLA-DR on Iba1+ cells	2 years
Clusters of activated microglia and macrophages will be studied in patients with ICANS	Clusters of activated microglia and macrophages will be studied in patients with ICANS	2 years

Collaborators and Investigators

• Sponsor: University of Freiburg

Publications and helpful links

General Publications

• Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hollaender N, Gowda M, Stefanelli T, Lee SJ, Teshima T, Locatelli F; REACH3 Investigators. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2021 Jul 15;385(3):228-238. doi: 10.1056/NEJMoa2033122.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Actual): April 5, 2023
• Study Completion (Actual): April 5, 2023

Study Registration Dates

• First Submitted: March 30, 2023
• First Submitted That Met QC Criteria: March 30, 2023
• First Posted (Actual): April 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 16, 2023
• Last Update Submitted That Met QC Criteria: May 14, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Brain Diseases
• Other Study ID Numbers: UKLFR02022021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No