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

NCT ID: NCT07173166

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-06
• Study Completion Date: 2028-09-30

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.

Conditions

Hematologic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: SINGLE

Study Groups

Physical activity

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.

Group Type: EXPERIMENTAL

Physical activity

Intervention Type: 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 and nutrition

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.

Group Type: EXPERIMENTAL

Physical activity

Intervention Type: 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 and nutrition

Intervention Type: 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.

Control

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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 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.

Intervention Type: 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 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.

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto de Investigacion Sanitaria INCLIVA

OTHER

Sponsor Role: lead

Responsible Party

Marina Hernández Aliaga

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

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

Role: PRINCIPAL_INVESTIGATOR

Instituto de Investigacion Sanitaria INCLIVA

Locations

Hospital Clínico Universitario de Valencia

Valencia, Valencia, Spain

Site Status: RECRUITING

Hospital Universitario y Politécnico La Fe

Valencia, Valencia, Spain

Site Status: ACTIVE_NOT_RECRUITING

Countries

Spain

Central Contacts

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

Role: CONTACT

marinaheral27@gmail.com

+34 655707385

Facility Contacts

Marina Hernández Aliaga

Role: primary

marinaheral27@gmail.com

+34 655707385

References

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.

Reference Type: BACKGROUND

PMID: 40077029 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33167544 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34923107 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 39474369 (View on PubMed)

Other Identifiers

2025/185

Identifier Type: -

Identifier Source: org_study_id