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

Official title

Randomized, Multicenter, Controlled Clinical Trial to Evaluate the Efficacy of Non-Pharmacological Interventions on Neurotoxicity Associated With CAR-T Therapy in Hematologic Patients

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.

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.

Interventions

• Other Physical activity
  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 e
• Other Physical activity and nutrition
  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 o

Primary outcome measures

• Incidence and severity of neurotoxicity as assessed by American Society for Transplantation and Cellular Therapy (ASCT) Immune Effector Cell-Associated Encephalopathy (ICE) consensus grading system [Time frame: At baseline and from the infusion of treatment until 15 days after CAR-T therapy.]

Secondary outcome measures (5)

• Functional independence as assessed by the Lawton and Brody Instrumental Activities of Daily Living (IADL) scale [Time frame: At baseline and from the infusion of treatment until 15 days after CAR-T therapy.]
• Physical activity level as assessed by the International Physical Activity Questionnaire (IPAQ) [Time frame: At baseline and from the infusion of treatment until 15 days after CAR-T therapy.]
• Nutritional status as assessed by the Patient-Generated Subjective Global Assessment (PG-SGA) [Time frame: At baseline and from the infusion of treatment until 15 days after CAR-T therapy.]
• Quality of life as assessed by the Short Form 12 (SF-12) [Time frame: At baseline and from the infusion of treatment until 15 days after CAR-T therapy.]
• Adherence to interventions [Time frame: At baseline and from the infusion of treatment until 15 days after CAR-T therapy.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Supportive care

Study locations

Spain · 2 centers

• Hospital Clínico Universitario de Valencia — Valencia
• Hospital Universitario y Politécnico La Fe — Valencia

Publications

• Borsati A, Murri A, Natalucci V, Cerulli C, Barbieri E, Lucertini F, Lanza M, Parisi A, Galvani C, Buono P, Mancini A, Fischetti F, Poli L, Di Blasio A, Iannaccone A, Avancini A, Mauri C, Ferri Marini C, Grazioli E. The Effect of Exercise-Based Interventions on Health-Related Quality of Life of Patients with Hematological Malignancies: A Systematic Review and Meta-Analysis. Healthcare (Basel). 202 PMID 40077029
• Richards J, Arensberg MB, Thomas S, Kerr KW, Hegazi R, Bastasch M. Impact of Early Incorporation of Nutrition Interventions as a Component of Cancer Therapy in Adults: A Review. Nutrients. 2020 Nov 5;12(11):3403. doi: 10.3390/nu12113403. PMID 33167544
• Hayden PJ, Roddie C, Bader P, Basak GW, Bonig H, Bonini C, Chabannon C, Ciceri F, Corbacioglu S, Ellard R, Sanchez-Guijo F, Jager U, Hildebrandt M, Hudecek M, Kersten MJ, Kohl U, Kuball J, Mielke S, Mohty M, Murray J, Nagler A, Rees J, Rioufol C, Saccardi R, Snowden JA, Styczynski J, Subklewe M, Thieblemont C, Topp M, Ispizua AU, Chen D, Vrhovac R, Gribben JG, Kroger N, Einsele H, Yakoub-Agha I. M PMID 34923107
• Han MW, Jeong SY, Suh CH, Park H, Guenette JP, Huang RY, Kim KW, Yoon DH. Incidence of immune effector cell-associated neurotoxicity among patients treated with CAR T-cell therapy for hematologic malignancies: systematic review and meta-analysis. Front Neurol. 2024 Oct 15;15:1392831. doi: 10.3389/fneur.2024.1392831. eCollection 2024. PMID 39474369

Identifiers

NCT: NCT07173166 · 2025/185

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗