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

NCT04614987 | Terminated

• 2 other identifiers: 202009118K12CA167540
• Study Type: observational
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neurotoxicity

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (8)

• Cross-sectional biomarker profiles

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

• Cross-sectional imaging profile

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

• Cytokine profiles

  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)

  Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)

• Changes in cognitive assessment as measured by Trail Making Test A/B

  Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)

Study Arms (1)

Participants undergoing CAR T transfusion

Participants will undergo baseline examination followed by evaluations between Days 3 and 5 post-transfusion, on Day 30 post-transfusion date (PTD), PTD 90, and PTD 180. At baseline this will include plasma testing, lumbar puncture (voluntary), neuroimaging (voluntary) and neuropsychiatric performance testing (voluntary). Between post-transfusion Day 3 and day 5, participants will undergo repeat exam, plasma testing, lumbar puncture (voluntary), and neuroimaging (voluntary). Day 30 testing will again test all modalities, including serum, CSF/lumbar puncture (voluntary), brain imaging (voluntary), and formal neuropsychiatric performance testing (voluntary). Finally, Day 90 and 180 will repeat serum testing, brain imaging, and formal neuropsychological performance testing.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants scheduled to undergo treatment at Siteman Cancer Center at Washington University School of Medicine with tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, or lisocabtagene maraleucel.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• McDonnell Center: collaborator
• Paula and Roger Riney Blood Cancer Research: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Neurotoxicity Syndromes

Condition Hierarchy (Ancestors)

Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Study Officials

• Armin Ghobadi, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2020
• First Posted: November 4, 2020
• Study Start: February 25, 2021
• Primary Completion: September 13, 2023
• Study Completion: September 13, 2023
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 3 months after the start of the study with no end date.
• Access Criteria: This will be made available to researchers who provide a methodologically sound proposal which has been approved by an independent review committee. Interested parties may reach out to Armin Ghobadi, M.D. arminghobadi@wustl.edu

Locations

US (1)