Serum Neurofilament Light (NfL) as a Marker for Brain Injury in Individuals Undergoing Chimeric Antigen Receptor-modified T Therapy

Washington University School of Medicine17 enrolled

Overview

The investigators propose that immune effector cell-associated neurotoxicity syndrome (ICANS) is predicated upon the early loss of blood brain barrier (BBB) integrity with subsequent monocyte infiltration leading to cross-activation of native glial cells. Glial overstimulation leads to neuroinflammation, synaptic dysfunction, and ultimately neuronal injury.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Neurotoxicity

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Clinically scheduled to undergo treatment with tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, or lisocabtagene maraleucel. * At least 18 years of age. * Able and willing to undergo study testing (blood draws, lumbar punctures, neuro-psychiatric testing, and neuroimaging with MRI) * Participants of childbearing potential without documented history of menopause or hysterectomy who choose to participate must not be pregnant at screening and must agree to avoid becoming pregnant prior to scanning. * Able to understand and willing to sign an IRB-approved written informed consent document. Exclusion Criteria: * Has any condition that, in the Investigator's opinion, could increase risk to the participant, limit the participant's ability to tolerate the experimental procedures, or interfere with the collection/analysis of the data (for example, participants unable to lie flat for the duration of the MRI scan). * Contraindications to MR imaging (e.g. electronic medical devices, inability to lie still for long periods) that make it unsafe for the individual to participate. Patients with pacemakers may only be scanned if approved by CCIR staff and radiology review. * Severe claustrophobia. * History of multiple sclerosis, Parkinson's disease, dementia (including Alzheimer's disease, frontotemporal dementia, and Pick's disease), or motor neuron disease including amyotrophic lateral sclerosis (ALS) * For the lumbar puncture associated with the study only: contraindications to lumbar puncture (e.g. platelets \<r 50,000/mm3, INR \> 1.5, evidence of midline shift on imaging, presence of local infection at LP site, history of baclofen pump, history of significant spinal surgery/hardware which would preclude safe bedside lumbar puncture). If a contraindication to lumbar puncture develops while on study, patient may remain on study but will be barred from a lumbar puncture until that contraindication resolves. * Pregnant * Enrolled in an interventional study of a drug targeting neurotoxicity

Locations (1)

Washington University School of Medicine

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Percent changes in given biomarker levels

* This includes serum (GFAP and NfL) and CSF biomarkers (NfL, VILIP-1, YKL-40, TREM2, and Neurogranin) measured using a single molecule array in pg/ml * Descriptive statistics will be used to summarize a given biomarker level at different time points.

Time frame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)

Secondary Outcomes

Cross-sectional biomarker profiles

-Serum (GFAP, NfL) and CSF biomarkers (NfL, VILIP-1, YKL-40, TREM2, and Neurogranin) as measured using a single molecule array in pg/ml will be compared between participants who develop ICANS compared to participants who do not develop ICANS using descriptive statistics

Time frame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)

Cross-sectional imaging profile

-Diffusion basis spectrum imaging (DBSI) separates the point diffusion properties of water by magnitude and direction to provide a non-invasive measurement of cellularity, extracellular edema, and axonal integrity/myelination in μm\^2/msec. All three components will then be compared between participants who develop ICANS compared to participants who do not develop ICANS using descriptive statistics

Time frame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)

Cytokine profiles

-Elisa-based assays will measure the CSF cytokine profile measurements of IL-2, IL-6, IL10, IFN-y, TNFα, GM-CSF (ng/ml), with descriptive statistics used to compare between participants who develop ICANS compared to participants who do not develop ICANS

Time frame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)

Changes in cognitive assessment as measured by Symbol Digit Modalities Test (SDMT)

-The SDMT is a brief written test where participants use a key to match abstract symbols paired with numbers. The scale ranges from 0 to 110, with higher scores reflecting better function. By doing so, an indirect measure of attention, processing speed, motor speed, and visual scanning is obtained. Scores on formal testing will be then be analyzed in conjunction with quantification of imaging features (as parceled using DBSI) observed between participants who develop ICANS compared to participants who do not develop ICANs

Data from ClinicalTrials.gov

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