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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Hematologic Neoplasms

Detailed Description

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.

• Study Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Relapsed or refractory DLBCL or ALL with intent to undergo commercially available CAR-T cell therapy

Description

Inclusion Criteria:

1. R/R DLBCL or R/R ALL diagnosis
2. Scheduled to receive commercial CAR-T cell therapy (Axi-Cel or Tisagenlecleucel)
3. greater than or equal to 19 years of age
4. Legally licensed to drive for at least 5 years
5. Previously drove an average of 50 miles/week or at least 1 hour/week
6. Normal visual acuity (20/40 or better)
7. Fluent in English

Exclusion Criteria:

(1) Cognitive impairment (MMSE score < 21) prior to baseline assessment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
CAR-T patients; 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?

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

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Principal Investigator: Matthew Lunning, DO, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2020
• Primary Completion (Actual): May 25, 2021
• Study Completion (Actual): May 25, 2021

Study Registration Dates

• First Submitted: February 14, 2020
• First Submitted That Met QC Criteria: February 14, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 18, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: 0157-19-FB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No