ICANS, Grade UnspecifiedNCT05811117
Multicenter Study Using IMC to Analyze the Impact of ICANS on Microglia
An observational study of ICANS, Grade Unspecified and CAR T-Cell-Related Encephalopathy Syndrome, run by University of Freiburg at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- ICANS, Grade Unspecified, CAR T-Cell-Related Encephalopathy Syndrome
- Type of treatment
- Injection or infusion
- How many people
- 8 participants
- Where
- 1 siteGermany
- Study dates
- 12 Apr 2021to 5 Apr 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients that had developed ICANS after CAR T cell infusion will be analyzed.
Who may be able to join
- Patients that had developed ICANS
- CAR T cell infusion for lymphoid malignancy (NHL or ALL)
Who cannot join
- Lack of consent of patient or legal guardian
Trial locations and contacts
1 site in 1 country.
Germany1 site
Freiburg University Medical Center
Freiburg im Breisgau, Baden-Wurttemberg, 79106
About this study
Official title: 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.
Read the 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.
- Being tested
- There will be no intervention as we will study patients that undergo autopsy after CAR T cell infusion.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
There will be no intervention as we will study patients that undergo autopsy after CAR T cell infusion.Diagnostic test
We will study patients that undergo autopsy after CAR T cell infusion.
What is being measured
The primary outcome is the main question the study is designed to answer.
HLA-DRA and HLA-DR on Iba1+ cells
We will study HLA-DRA and HLA-DR on Iba1+ cells
Measured: 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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2023
- Study start12 Apr 2021
- Primary completion5 Apr 2023
- Study completion5 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ICANS, Grade UnspecifiedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Freiburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Zeiser, University of Freiburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05811117
- Sponsor's protocol ID
- UKLFR02022021
- Status last verified
- May 2023
- First submitted
- 30 Mar 2023
- Last updated
- 16 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 34260836
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Study Using Imaging Mass Cytometry to Analyze the Impact of ICANS on Microglia
- ClinicalTrials.gov ID
- NCT05811117
- Acronym / sponsor ID
- UKLFR02022021
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of FreiburgUniversity, hospital or other
- Study start
- 12 Apr 2021 (actual)
- Primary completion
- 5 Apr 2023 (actual)
- Study completion
- 5 Apr 2023 (actual)
- First posted
- 13 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients that had developed ICANS after CAR T cell infusion will be analyzed.
Key inclusion criteria (2 listed)
- Patients that had developed ICANS
- CAR T cell infusion for lymphoid malignancy (NHL or ALL)
Key exclusion criteria (1 listed)
- Lack of consent of patient or legal guardian
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| There will be no intervention as we will study patients that undergo autopsy after CAR T cell infusion.We will study patients that undergo autopsy after CAR T cell infusion. | Diagnostic test | – |
Primary outcome
HLA-DRA and HLA-DR on Iba1+ cells
Time frame: 2 years
We will study HLA-DRA and HLA-DR on Iba1+ cells
Clusters of activated microglia and macrophages will be studied in patients with ICANS
Time frame: 2 years
Clusters of activated microglia and macrophages will be studied in patients with ICANS
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2023.
- Results publication: PubMed 34260836Zeiser 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of ICANS, Grade Unspecified and CAR T-Cell-Related Encephalopathy Syndrome, run by University of Freiburg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HLA-DRA and HLA-DR on Iba1+ cells (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05811117, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2023.