Clinical trial NCT05811117: Multicenter Study Using IMC to Analyze the Impact of ICANS on Microglia
Official title: Multicenter Study Using Imaging Mass Cytometry to Analyze the Impact of ICANS on Microglia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: ICANS, Grade Unspecified
CAR T-Cell-Related Encephalopathy Syndrome
Lead sponsor: University of Freiburg
Sponsor class: OTHER
First posted: 2023-04-13
Enrollment: 8
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients that had developed ICANS after CAR T cell infusion will be analyzed.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: HLA-DRA and HLA-DR on Iba1+ cells
timeFrame: 2 years
measure: Clusters of activated microglia and macrophages will be studied in patients with ICANS
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Freiburg University Medical Center
state: Baden Württemberg
Study officials:
References:
citation: 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.