Clinical trial NCT04614987: Serum Neurofilament Light (NfL) as a Marker for Brain Injury in Individuals Undergoing Chimeric Antigen Receptor-modified T Therapy
Official title: Serum Neurofilament Light (NfL) as a Marker for Brain Injury in Individuals Undergoing Chimeric Antigen Receptor-modified T Therapy
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Neurotoxicity
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: McDonnell Center
name: Paula and Roger Riney Blood Cancer Research
name: National Cancer Institute (NCI)
First posted: 2020-11-04
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent changes in given biomarker levels
timeFrame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)
Secondary outcomes:
measure: Cross-sectional biomarker profiles
timeFrame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)
measure: Cross-sectional imaging profile
timeFrame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)
measure: Cytokine profiles
timeFrame: From baseline to up to 180 days post-transfusion (estimated to be 7 months)
measure: Changes in cognitive assessment as measured by Symbol Digit Modalities Test (SDMT)
timeFrame: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
measure: Changes in cognitive assessment as measured by Trail Making Test A/B
timeFrame: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
measure: Changes in cognitive assessment as measured by Letter-Number Sequencing
timeFrame: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
measure: Changes in cognitive assessment as measured by Hopkins Verbal Learning Test-Received (HVLT-R3)
timeFrame: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
measure: Changes in cognitive assessment as measured by Montreal-Cognitive Assessment (MocA)
timeFrame: Baseline, 30 days, 90 days, and 180 days post-transfusion (estimated to be 7 months)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Armin Ghobadi, M.D.
role: PRINCIPAL_INVESTIGATOR
References: