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

NCT07173166 | Recruiting

• 1 other identifier: 2025/185
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

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.

Conditions

Hematologic Cancer

Keywords

CAR-T therapy; Neurotoxicity; Nutrition; Physical activity

Outcome Measures

Primary Outcomes (1)

• 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.

  At baseline and from the infusion of treatment until 6 months after CAR-T therapy.

Secondary Outcomes (5)

• 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.

• 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.

• 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.

• 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.

• Adherence to interventions

  At baseline and from the infusion of treatment until 6 month after CAR-T therapy.

Other Outcomes (2)

• Length of initial hospital stay

  From the infusion of treatment until 6 months after CAR-T therapy.

• Number of hospital readmissions

  From the infusion of treatment until 6 months after CAR-T therapy.

Study Arms (3)

Physical activity

EXPERIMENTAL

Patients assigned to intervention group A will follow a supervised programme of physical activity and exercise at home and during their hospital stay. These recommendations are designed and supervised by a physiotherapist. The programme will include three weekly aerobic exercise sessions and two resistance exercise sessions, as recommended in the literature. Each session will last approximately 35 minutes and will include a warm-up, training and cool-down. All patients will follow the same exercise programme, which will be adapted to a basic, intermediate and advanced level to adapt to the patients' physical condition. The loads, intensity and number of sets will be adapted for each level. The programme is scheduled to commence one month prior to the initiation of CAR-T therapy. It is recommended that patients adhere to the professional's guidelines for a period of at least one month following treatment.

Other: Physical activity

Physical activity and nutrition

EXPERIMENTAL

The intervention combines a structured physical activity programme with individualised nutritional recommendations based on the Mediterranean diet. These recommendations are designed and supervised by a nutritionist and a physiotherapist. The macronutrient distribution followed standard guidelines (50-55% carbohydrates, 30-35% fats, 10-15% proteins), emphasising vegetables, fruits, legumes, cereals, dairy, lean meats, fish, nuts, and olive oil. Each food group contributes bioactive compounds with anti-inflammatory and antioxidant properties, including lycopene, quercetin, anthocyanins, genistein, ferulic acid, SCFAs, omega-3 fatty acids and polyphenols. These have been shown to mitigate oxidative stress, inflammation and toxicological effects, thereby supporting cardio. The programme is scheduled to commence one month prior to the initiation of CAR-T therapy. It is recommended that patients adhere to the professional's guidelines for a period of at least one month following treatment.

Other: Physical activity; Other: Physical activity and nutrition

Control

NO INTERVENTION

The control group will serve to establish a baseline for identifying clinical, demographic, and response patterns of the studied variables. All procedures and interventions will be conducted in accordance with the center's standard clinical practice.

Interventions

Physical activity OTHER

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; Physical activity and nutrition

Physical activity and nutrition OTHER

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.

Physical activity and nutrition

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto de Investigacion Sanitaria INCLIVA: lead

Study Sites (2)

Hospital Clínico Universitario de Valencia

Valencia, Valencia, 46010, Spain

RECRUITING

Hospital Universitario y Politécnico La Fe

Valencia, Valencia, 46026, Spain

ACTIVE NOT RECRUITING

Related Publications (4)

• 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). 2025 Feb 21;13(5):467. doi: 10.3390/healthcare13050467.

  PMID: 40077029 BACKGROUND

• 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 BACKGROUND

• 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. Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA). Ann Oncol. 2022 Mar;33(3):259-275. doi: 10.1016/j.annonc.2021.12.003. Epub 2021 Dec 16.

  PMID: 34923107 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Hematologic Neoplasms; Neurotoxicity Syndromes; Motor Activity

Interventions

Exercise; Nutritional Status

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Health Status; Demography; Population Characteristics

Study Officials

• Marina Hernandez Aliaga, RN, MSc, PhD(c)

  Instituto de Investigacion Sanitaria INCLIVA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marina Hernandez Aliaga, RN, MSc, PhD(c)

CONTACT

+34 655707385; marinaheral27@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The intervention is assigned and administered by external staff. Investigators do not participate in delivering the interventions. Outcome assessors are also blinded. Participants are aware of their assigned intervention.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 16, 2025
• First Posted: September 15, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: March 10, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)