Clinical trial NCT04275154: Immunological Parameters, Neurocognitive Changes, Activity, & Driving Fitness in Patients Undergoing CAR-T Cell Therapy
Official title: Evaluating Immunological Parameters, Neurocognitive Changes, Activity Levels, and Driving Fitness in Hematological Malignancy Patients Undergoing Chimeric Antigen Receptor (CAR)-T Cell Therapy
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Hematologic Neoplasms
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2020-02-19
Enrollment: 0
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Relapsed or refractory DLBCL or ALL with intent to undergo commercially available CAR-T cell therapy

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate the relationship between immunologic markers of CRS and ICANS in hematologic malignancy patients undergoing CAR-T cell therapy
timeFrame: 6 weeks
measure: Evaluate the relationship between neurologic markers of CRS and ICANS in hematologic malignancy patients undergoing CAR-T cell therapy
timeFrame: 6 weeks
measure: Activity level parameters- daily number of steps
timeFrame: 6 weeks
measure: On-Road Driving Performance
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Nebraska
name: Matthew Lunning, DO
role: PRINCIPAL_INVESTIGATOR
References: