Immunological Parameters, Neurocognitive Changes, Activity, & Driving Fitness in Patients Undergoing CAR-T Cell Therapy

Study Overview
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Brief Summary
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Chimeric antigen receptor (CAR) T-cell therapy is a promising new treatment that re-programs patient immune cells to target and destroy cancer cells. Importantly, CAR T-cell therapy has improved overall response rate and durability in patients with refractory or relapsed diffuse large B-cell lymphoma (DLCBL) and acute lymphoblastic leukemia (ALL). Toxicities following CAR T-cell therapy remain a major limitation to expanding access to this promising cancer treatment. Biological predictors of CAR-T-related toxicities are currently lacking, and it remains unknown whether CAR-T-related toxicities lead to subsequent impairments in instrumental activities of daily living. The overarching goal of this project aims to link biological predictors of CAR-T-related toxicities to instrumental activities of daily living, such as physical activity and driving performance. The current study proposes to test the hypothesis that CAR T-cell therapy causes changes in immunological and neurological markers that predict changes in physical activity levels and driving performance.

Detailed Description
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Study specific aims are: (1A) Evaluate changes in serum inflammatory cytokine protein markers in patients receiving CAR T-cell therapy; (1B) Evaluate changes in electroencephalographic and radiologic markers of CAR-T-related toxicities in comparison to neurocognitive function following CAR T-cell therapy; (2A) Assess changes in activity levels using actigraphy/accelerometry to continuously monitor physical activity; and (2B) Assess changes in driving performance using a standardized on-road instrumented vehicle drive. Patients (n=20) will be recruited into the study if they are diagnosed with relapsed or refractory DLBCL or ALL, and scheduled to undergo commercially-available CAR T-cell therapy. The following measures will be completed during primary study visits: prior to apheresis (T0) and 8-weeks post CAR-T cell infusion (T6). (1) blood inflammatory proteins; (2) brain wave recordings (or EEG), brain imaging, and neurocognitive assessment; (3) free-living activity levels; and (4) driving performance and safety. EEG will assess neural activity patterns of brain dysfunction; brain imaging will look for brain abnormalities; neurocognitive assessments will evaluate changes in thinking, concentration, and memory. A research-grade activity monitor will be used to assess activity levels. Driving performance and safety will be evaluated using a driving simulator and an on-road vehicle designed to monitor behavior while drivers complete a driving course. Analyses will assess changes between study visits, as well as relationships between immunological, neurological, activity, and driving measures.

Official Title
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Evaluating Immunological Parameters, Neurocognitive Changes, Activity Levels, and Driving Fitness in Hematological Malignancy Patients Undergoing Chimeric Antigen Receptor (CAR)-T Cell Therapy

Conditions
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Hematologic Neoplasms

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: R/R DLBCL or R/R ALL diagnosis Scheduled to receive commercial CAR-T cell therapy (Axi-Cel or Tisagenlecleucel) greater than or equal to 19 years of age Legally licensed to drive for at least 5 years Previously drove an average of 50 miles/week or at least 1 hour/week Normal visual acuity (20/40 or better) Fluent in English Exclusion Criteria: (1) Cognitive impairment (MMSE score < 21) prior to baseline assessment

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CAR-T patients<br>Relapsed or refractory Diffuse large B-cell lymphoma (DLBCL) or acute lymphoblastic leukemia (ALL) with intent to undergo commercially available CAR-T cell therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the relationship between immunologic markers of CRS and ICANS in hematologic malignancy patients undergoing CAR-T cell therapy | Change in serum inflammatory cytokine (IL-2, IL-4, IL-6, IL-10, TNF-alpha IFN-gamma, and IL-17A) concentrations from baseline | 6 weeks | 
| Evaluate the relationship between neurologic markers of CRS and ICANS in hematologic malignancy patients undergoing CAR-T cell therapy | Change in number of pathological EEG events from baseline | 6 weeks | 
| Activity level parameters- daily number of steps | Change in daily number of steps from baseline | 6 weeks | 
| On-Road Driving Performance | Change in number of driving safety errors from baseline | 6 weeks |