Randomized, Multicenter, Controlled Clinical Trial to Evaluate the Efficacy of Non-Pharmacological Interventions on Neurotoxicity Associated With CAR-T Therapy in Hematologic Patients
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 338
- 试验地点
- 2
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients, aged 18 to 80 years.
- •Diagnosed with a hematological condition.
- •Initiating antineoplastic treatment with CAR-T cell therapy.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Physical activity (Other)
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.
干预措施: Physical activity (Other)
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.
干预措施: Physical activity and nutrition (Other)
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.
结局指标
主要结局
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
时间窗: At baseline and from the infusion of treatment until 15 days after CAR-T therapy.
Patients will undergo a standardised neurological evaluation. The American Society for Transplantation and Cellular Therapy (ASCT) classifies immune effector cell-associated encephalopathy (ICE), which grades the associated neurotoxicity from 1 to 4. It consists of five domains: ICE score, decreased level of consciousness, convulsions, motor findings and elevated intracranial pressure or cerebral oedema. The ICE score evaluates five cognitive domains (orientation, object naming, following instructions, writing and attention) with a maximum score of 10 points.
次要结局
- 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 15 days 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 15 days 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 15 days 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 15 days after CAR-T therapy.)
- Adherence to interventions(At baseline and from the infusion of treatment until 15 days after CAR-T therapy.)
研究者
Marina Hernández Aliaga
Principal Investigator
Instituto de Investigacion Sanitaria INCLIVA