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

Instituto de Investigacion Sanitaria INCLIVA100 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Interventions

Physical activityOTHER

Patients assigned to intervention group A will follow a supervised programme of physical activity and exercise at home and during hospitalisation. All patients will follow the same exercise programme, which will be adapted to a basic, intermediate and advanced level to suit the patients' physical condition. The loads, intensity and number of sets will be adapted to each level. Aerobic exercise will consist of walking and/or cycling at an intensity of between two and five on the Borg perceived exertion (RPE) scale. Resistance exercise will consist of one session focusing on the trunk and upper limbs, and another on the lower limbs. Both sessions will include seven exercises, performed at an intensity of between three and four on the Borg RPE scale.

Physical activity and nutritionOTHER

The intervention integrates a structured physical activity programme with individualized nutritional recommendations based on the Mediterranean diet. Macronutrient distribution was 50-55% carbohydrates, 30-35% fats, and 10-15% proteins. The protocol emphasized the intake of vegetables (≥2 servings/day, 200 g each), fruits (1-2 servings/day, 150 g each), legumes (≥3 servings/week, 150 g cooked), whole grains (1-2 servings/meal, 40-60 g), and low-fat dairy products (1-2 servings/day; 200 ml milk or 125 g yoghurt). Lean meats were prescribed at 3-4 servings/week (100-125 g each), fish and seafood at 4 servings/week (150 g each), nuts at 3-7 servings/week (30 g each), and olive oil as the principal fat source (≤4 tbsp/day). Micronutrients and bioactive compounds from these foods, including antioxidants, polyphenols, and essential fatty acids, were recognized as pivotal for modulating protective mechanisms and mitigating toxicological effects.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Incidence and severity of neurotoxicity as assessed by CTCAE v5.0 and Immune Effector Cell-Associated Encephalopathy (ICE) score following 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.