NCT07375628

Brief Summary

This is a phase 4 non-interventional single center trial. We aim to prospectively include patients scheduled to undergo CAR-T therapy at ME CAST, Karolinska University Hospital Huddinge, to study ICANS. Because ICANS develops rapidly, inclusion during this potentially life-threatening phase would not be feasible; patients must therefore be enrolled before they start treatment. We aim to include patients who are clinically at high risk of developing ICANS. The risk of ICANS is assessed based on diagnosis, tumor burden, CAR-T product, and inflammatory status prior to treatment initiation. We plan to compare patients who develop ICANS grade 2-4 with patients who develop no ICANS or at most grade 1. Patients will undergo Positron Emission Tomography (PET) with two different tracers: (1) PBR28 for TSPO, which provides a measure of brain inflammation-this ligand binds to microglial cells-and (2) 11C-UCB-J for SV2A, which provides a measure of synaptic density in the brain. The results will be compared with magnetic resonance imaging. We will collect blood, bone marrow and cerebrospinal fluid (CSF) samples from this patient cohort. Samples will be taken from all patients before, during, and after CAR-T treatment. Participation in the study also includes computer-based cognitive testing, neuropsychological evaluation and genetic testing to determine whether the patient has receptors allowing binding of the TSPO radioligand used during PET imaging.

Trial Health

65
Monitor

Trial Health Score

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

Enrollment
10

participants targeted

Target at below P25 for all trials

Timeline
37mo left

Started Feb 2026

Typical duration for all trials

Status
not yet recruiting

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress8%
Feb 2026May 2029

First Submitted

Initial submission to the registry

January 22, 2026

Completed
7 days until next milestone

First Posted

Study publicly available on registry

January 29, 2026

Completed
3 days until next milestone

Study Start

First participant enrolled

February 1, 2026

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2028

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2029

Last Updated

January 29, 2026

Status Verified

January 1, 2026

Enrollment Period

2.2 years

First QC Date

January 22, 2026

Last Update Submit

January 22, 2026

Conditions

CAR T Cell TherapyICANSCognitive and Executive Dysfunction

Keywords

IcansCAR T cell therapyFatigueCognitive dysfunctionPET scan

Outcome Measures

Primary Outcomes (1)

  • To perform in deep descriptive analysis of patients developing ICANS grade 2-4 compared to patients with no ICANS or ICANS grade 1.

    The primary aim is to perform in-depth descriptive analyses in patients with ICANS grades 2-4 and 0-1. The scientific objective is to investigate synaptic density, inflammation, and activation of glial cells, which according to our hypothesis are linked to fatigue and cognitive dysfunction after ICANS. Our hypothesis is that these symptoms are caused by immune activation in the brain, which can be detected, among other methods, by PET imaging. We further hypothesize that this inflammation leads to altered neuronal connectivity with synaptic involvement.

    2028

Study Arms (1)

Adult patients undergoing CAR T cell therapy in Region Stockholm

This project includes only adult patients (\>20 years) in Region Stockholm. Participants will be patients with various hematologic diagnoses undergoing CAR-T. These patients are identified during routine care at ME CAST, Karolinska University Hospital.

Eligibility Criteria

Age20 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Participants will be patients with various hematologic diagnoses undergoing CAR-T. These patients are identified during routine care at ME CAST, Karolinska University Hospital. Only adults (over 20 years) will be included.

You may qualify if:

  • Age \> 20
  • Planned to undergo CAR-T treatment
  • No known prior CNS diseases or head trauma
  • Capable of receiving tailored information about the research project and signing informed consent

You may not qualify if:

  • Age under 20 years
  • The patient has previously indicated they wish to refrain from research participation
  • Another concurrent neuroinflammatory or neurodegenerative disease, or malignant disease (other than the underlying condition) in the central nervous system

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • 1. Kazzi C, Kuznetsova V, Siriratnam P, Griffith S, Wong S, Tam CS, Alpitsis R, Spencer A, O'Brien TJ, Malpas CB, Monif M. Cognition following chimeric antigen receptor T-cell therapy: A systematic review. J Autoimmun. 2023 Nov;140:103126. doi: 10.1016/j.jaut.2023.103126. Epub 2023 Oct 12. PMID: 37837807. 2. Gust J, Ponce R, Liles WC, Garden GA and Turtle CJ (2020) Cytokines in CAR T Cell-Associated Neurotoxicity. Front. Immunol. 11:577027. doi: 10.3389/fimmu.2020.577027 3. Morbelli, S., Gambella, M., Raiola, A. M., Ghiggi, C., Bauckneht, M., Di Raimondo, T., Lapucci, C., Sambuceti, G., Inglese, M., & Angelucci, E. Brain FDG-PET findings in chimeric antigen receptor T-cell therapy neurotoxicity for diffuse large B-cell lymphoma. Journal of Neuroimaging 2023 DOI: 10.1111/jon.13135 4. Vinnakota, J.M., Biavasco, F., Schwabenland, M. et al. Targeting TGFβ-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity syndrome. Nat Cancer 5, 1227-1249 (2024). https://doi.org/10.1038/s43018-024-00764-7 5. Chauveau, F., Winkeler, A., Chalon, S. et al. PET imaging of neuroinflammation: any credible alternatives to TSPO yet?. Mol Psychiatry 30, 213-228 (2025). https://doi.org/10.1038/s41380-024-02656-9 6. Vardy J, Wong K, Yi QL, Park A, Maruff P, Wagner L, Tannock IF. Assessing cognitive function in cancer patients. Support Care Cancer. 2006 Nov;14(11):1111-8. doi: 10.1007/s00520-006-0037-6. Epub 2006 Mar 15. PMID: 16538498. 7. Meyer JH, et al. Neuroinflammation in psychiatric disorders: PET imaging and promising new targets. Lancet Psychiatry. 2020 Dec;7(12):1064-1074. doi: 10.1016/S2215-0366(20)30255-8. Epub 2020 Oct 21. PMID: 33098761; PMCID: PMC7893630. 8. Kreisl WC, et al. PET imaging of neuroinflammation in neurological disorders. Lancet Neurol. 2020 Nov;19(11):940-950. doi: 10.1016/S1474-4422(20)30346-X. PMID: 33098803; PMCID: PMC7912433. 9. Masdeu JC, Pascual B, Fujita M. Imaging Neuroinflammation in Neurodegenerative Disorders

    BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

blood, saliva, bone marrow, cerobrospinal fluid

MeSH Terms

Conditions

FatigueCognitive Dysfunction

Condition Hierarchy (Ancestors)

Signs and SymptomsPathological Conditions, Signs and SymptomsCognition DisordersNeurocognitive DisordersMental Disorders

Study Officials

  • Stephan Mielke, professor

    Karolinska

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ksenia Boriskina, MD

CONTACT

+46812380675ksenia.boriskina@regionstockholm.se

Kirsti Niemelä, study nurse

CONTACT

kirsti.niemela@regionstockholm.se

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Senior Consultant

Study Record Dates

First Submitted

January 22, 2026

First Posted

January 29, 2026

Study Start

February 1, 2026

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

May 1, 2029

Last Updated

January 29, 2026

Record last verified: 2026-01