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

The Washington University

Status: Terminated

Conditions: Neurotoxicity

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT04614987

K12CA167540 (U.S. NIH Grant/Contract)

202009118

Details and patient eligibility

About

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.

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

17 participants in 1 patient group

Participants undergoing CAR T transfusion

Description:

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.