NeurotoxicityNCT04614987
Serum Neurofilament Light (NfL) as a Marker for Brain Injury in Individuals Undergoing Chimeric Antigen Receptor-modified T Therapy
An observational study of Neurotoxicity, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurotoxicity
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2021to 13 Sep 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
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
- Medical subject headings
- Neurotoxicity Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to up to 180 days post-transfusion (estimated to be 7 months)
Secondary outcomes (8)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
This brief written test has participants connect lines between sequential numbers and/or letters in a given pattern. By doing so, an indirect measure of executive function tests task switching, visual search, scanning, processing speed, and visual attention 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
Measured: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
Changes in cognitive assessment as measured by Letter-Number Sequencing
-This brief cognitive test has participants listen to variable length strings of alphanumeric characters and repeat the characters back verbally in a specific order. They are then scored on the number of correct responses. Scores range from 0 to 21, with higher scores associated with improved cognitive function.
By doing so, a direct measure of working memory 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
Measured: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
Changes in cognitive assessment as measured by Hopkins Verbal Learning Test-Received (HVLT-R3)
-This approximately 30 minute long cognitive test has participants learn and free-recall a collection of words from different categories. By doing so, a direct measure of recall and memory is obtained. Scores range from 0 to 30, with higher scores indicating improved cognitive function. 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
Measured: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
Changes in cognitive assessment as measured by Montreal-Cognitive Assessment (MocA)
-This approximately 15 minute long cognitive test consists of both written and verbal sections. Participants are scored on the number of correct answers out of 30 (i.e. scores range from 0-30), with higher scores reflecting improved cognitive performance. By doing so, an indirect measure surveying multiple cognitive domains 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
Measured: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2020
- Study start25 Feb 2021
- Primary completion13 Sep 2023
- Study completion13 Sep 2023
Why it stopped: PI decided to close study early.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeurotoxicityStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- McDonnell Center, Paula and Roger Riney Blood Cancer Research, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Armin Ghobadi, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04614987
- Sponsor's protocol ID
- 202009118
- Other IDs
- K12CA167540
- Status last verified
- May 2025
- First submitted
- 7 Oct 2020
- Last updated
- 6 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data collected during the trial will be available, after deidentification. This will include the study protocol, statistical analysis plan, and analytic code, beginning 3 months after the start of the study with no end date. 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
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serum Neurofilament Light (NfL) as a Marker for Brain Injury in Individuals Undergoing Chimeric Antigen Receptor-modified T Therapy
- ClinicalTrials.gov ID
- NCT04614987
- Acronym / sponsor ID
- 202009118
- Conditions
- Neurotoxicity
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: PI decided to close study early.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- McDonnell Center, Paula and Roger Riney Blood Cancer Research, National Cancer Institute (NCI)
- Study start
- 25 Feb 2021 (actual)
- Primary completion
- 13 Sep 2023 (actual)
- Study completion
- 13 Sep 2023 (actual)
- First posted
- 4 Nov 2020 (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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Percent changes in given biomarker levels
Time frame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)
* 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.
8 secondary outcomes
Cross-sectional biomarker profiles
Time frame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)
Cross-sectional imaging profile
Time frame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)
Cytokine profiles
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)
Time frame: 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
Time frame: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
Changes in cognitive assessment as measured by Letter-Number Sequencing
Time frame: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
Changes in cognitive assessment as measured by Hopkins Verbal Learning Test-Received (HVLT-R3)
Time frame: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
Changes in cognitive assessment as measured by Montreal-Cognitive Assessment (MocA)
Time frame: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
Results and safety
The study was stopped early (reason given: PI decided to close study early.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2025.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data collected during the trial will be available, after deidentification. This will include the study protocol, statistical analysis plan, and analytic code, beginning 3 months after the start of the study with no end date. 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
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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.
Armin Ghobadi, M.D. principal investigator
Washington University School of Medicine
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 Neurotoxicity, run by Washington University School of Medicine at 1 site in United States.
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 5 inclusion and 7 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: stopped early, as of the sponsor's last update on 6 May 2025. 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 United States. 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 was stopped early (reason given: PI decided to close study early.). Results are not available in the source record.
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?
Percent changes in given biomarker levels (time frame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 May 2025.