Non-Pharmacological Interventions for Neurotoxicity in Hematologic Patients Receiving CAR-T Therapy

Not Applicable

Recruiting

• Conditions: Hematologic Cancer

• Registration Number: NCT07173166
• Lead Sponsor: Instituto de Investigacion Sanitaria INCLIVA

Brief Summary

The goal of this clinical trial is to learn if two non-pharmacological strategies can help reduce neurotoxicity caused by CAR-T cell therapy in adult patients with hematologic cancer, both sexes, aged 18 to 80 years. The strategies are:

* A structured physical activity program.

* A combination of physical activity and nutritional recommendations.

The main questions it aims to answer are:

* Does physical activity help lower the risk or severity of neurotoxicity after CAR-T therapy?

* Does combining physical activity with nutritional recommendations provide greater protection against neurotoxicity than physical activity alone?

Researchers will compare two intervention groups with a control group (no intervention) to see which approach is most effective in reducing neurotoxicity and improving recovery.

Participants will be randomly assigned to one of three groups using stratified randomization to ensure balanced clinical and demographic characteristics:

* Group A: Structured physical activity program.

* Group B: Structured physical activity program combined wuth nutritional recommendations.

* Group C: No intervention; used to establish baseline patterns.

Participants will be evaluated periodically by study professionals. Comprehensive records of symptoms, health measurements, and relevant lifestyle data will be maintained throughout the study.

Detailed Description

A parallel-group, multicenter and randomized controlled clinical trial will be conducted from July 2025 to July 2027. The study will evaluate the effectiveness of two non-pharmacological interventions in reducing neurotoxicity associated with CAR-T cell therapy in adult patients with hematologic cancer.

A total of 100 patients will be enrolled and randomly assigned into three groups using stratified randomization performed by an individual external to the research team.

The intervention will begin at least one month prior to CAR-T cell infusion. Participants will be followed weekly before, during, and for four weeks after therapy. Interventions and evaluations will be carried out in the same hospital where the patient receives treatment, and always by the same multidisciplinary team (hematologists, nurses, nutritionists, physiotherapists).

Primary and secondary outcomes will be assessed at baseline (prior to intervention), during treatment, and post-treatment follow-up. Written informed consent will be obtained from all participants before enrollment.

Study Timeline

• Study Start: 2025-07-06
• Study First Submitted: 2025-08-16
• Status Verified: 2025-09
• Study First Submitted QC: 2025-09-07
• Last Update Submitted: 2025-09-07
• Study First Posted: 2025-09-15
• Last Update Posted: 2025-09-15
• Primary Completion: 2027-07
• Study Completion: 2028-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Male and female patients, aged 18 to 80 years.
• Diagnosed with a hematological condition.
• Initiating antineoplastic treatment with CAR-T cell therapy.

Exclusion Criteria

• Presence of language barriers or physical and/or cognitive impairments that hinder the understanding of the interventions or prevent proper completion of the assessment tools used in the study.
• Pre-existing neurological or psychiatric comorbidities that may interfere with the evaluation of neurotoxic effects of the hematologic treatment.
• Concomitant treatment with additional neurotoxic drugs not related to the study protocol.
• History of abusive consumption of neurotoxic substances.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Incidence and severity of neurotoxicity as assessed by CTCAE v5.0 and Immune Effector Cell-Associated Encephalopathy (ICE) score following CAR-T therapy	At baseline and from the infusion of treatment until 6 months after CAR-T therapy.	Patients will undergo a standardised neurological assessment. Neurotoxicity will be graded according to version 5.0 of the Common Terminology Criteria for Adverse Events (CTCAE). The Immune Effector Cell-Associated Encephalopathy (ICE) score will also be used to evaluate five cognitive domains, for which the maximum possible score is 10. The following will be assessed: orientation (year, month, city, hospital; 4 points); object naming (three objects; 3 points); following commands (two-step command; 1 point); writing a coherent sentence (1 point); and attention (counting backwards from 100 in tens; 1 point). Lower ICE scores reflect greater neurological impairment.

Secondary Outcome Measures

Name	Time	Method
Functional independence as assessed by the Lawton and Brody Instrumental Activities of Daily Living (IADL) scale	At baseline and from the infusion of treatment until 6 months after CAR-T therapy.	Functional capacity will be assessed using the Lawton and Brody Instrumental Activities of Daily Living (IADL) scale . This instrument evaluates the patient's ability to perform eight instrumental activities essential for independent living (e.g., using the telephone, shopping, preparing meals, housekeeping, laundry, transportation, medication management, and financial management). Each item is scored as 0 (dependent) or 1 (independent), yielding a total score ranging from 0 (total dependence) to 8 (complete independence). Higher scores indicate greater independence and better functional status.
Physical activity level as assessed by the International Physical Activity Questionnaire (IPAQ)	At baseline and from the infusion of treatment until 6 months after CAR-T therapy.	Physical activity will be quantified using the International Physical Activity Questionnaire (IPAQ). The instrument comprises seven items and provides information on the time spent walking, performing moderate-intensity activities, vigorous-intensity activities, and sedentary behaviour during the last seven days. The results are expressed in metabolic equivalent task minutes per week (MET-min/week) and categorised into three levels of physical activity: * Low: no or insufficient activity.; * Moderate: ≥3 days of vigorous activity (20 minutes/day), ≥5 days of moderate activity or walking (30 minutes/day), or a combination reaching ≥600 MET-min/week.; * High: vigorous activity on ≥3 days achieving ≥1,500 MET-min/week, or 7 days of any combination reaching ≥3,000 MET-min/week.; This classification allows the identification of patients at risk of inactivity and facilitates monitoring of changes across the intervention.
Nutritional status as assessed by the Patient-Generated Subjective Global Assessment (PG-SGA)	At baseline and from the infusion of treatment until 6 months after CAR-T therapy.	Nutritional status will be evaluated using the Patient-Generated Subjective Global Assessment (PG-SGA), a tool that has been validated for the purpose of nutritional screening in oncohematology. The PG-SGA combines patient-reported data and clinician assessment, including weight changes, dietary intake, nutrition impact symptoms, functional capacity, and physical examination findings. Patients are categorised into three groups: well-nourished, moderately malnourished/at risk of malnutrition, or severely malnourished. The instrument facilitates the identification of patients requiring nutritional interventions, thereby providing a comprehensive overview of nutritional risk within the study population.
Quality of life as assessed by the Short Form 12 (SF-12)	At baseline and from the infusion of treatment until 6 months after CAR-T therapy.	Quality of life will be assessed using the Short Form 12 (SF-12) health survey. The SF-12 evaluates eight health domains, which are aggregated into two summary scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Each domain is scored according to the SF-12 scoring algorithm, resulting in standardized scores ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Adherence to interventions	At baseline and from the infusion of treatment until 6 month after CAR-T therapy.	The researcher collected attendance records, food records and self-reported activity levels as part of the follow-up of the subjects.

Trial Locations

Locations (2)

Hospital Clínico Universitario de Valencia; 🇪🇸 Valencia, Valencia, Spain

Hospital Universitario y Politécnico La Fe; 🇪🇸 Valencia, Valencia, Spain