Telematic Cognitive Training and Mindfulness in Pediatric Patients After CAR-T Cell Therapy, Single Hematopoietic Allogeneic Transplant or Chemotherapy

Официальное название

Randomized Controlled Clinical Trial of Telematic Cognitive Training and Mindfulness in Pediatric Patients After CAR-T Cell Therapy, Single Hematopoietic Allogeneic Transplant or Chemotherapy. The PsyCARTkids Project

Обзор

This randomized controlled clinical trial evaluates neurocognitive, biopsychological, and brain connectome outcomes in children and adolescents with acute lymphoblastic leukemia who have previously received Chimeric Antigen Receptor T-cell therapy (CAR T-cell therapy), chemotherapy, and/or hematopoietic stem cell transplantation (HSCT). Participants will receive a multimodal, telematic psychological intervention combining digital cognitive training and an adapted mindfulness-based emotional regulation program. Outcomes will be compared with a waitlist control group and intervention sequences will be counterbalanced: (1) cognitive training followed by mindfulness; and (2) mindfulness followed by cognitive training. Neurocognitive performance, emotional-behavioral functioning, executive functioning and EEG-based functional connectivity will be assessed at baseline, post-intervention and at 6 months follow-up.

Подробное описание

Children and adolescents treated for acute lymphoblastic leukemia are at increased risk of long-term neurocognitive, emotional, and psychosocial difficulties, particularly following intensive treatments such as CAR T-cell therapy, chemotherapy, and hematopoietic stem cell transplantation. Despite increasing survival rates, evidence-based psychological interventions targeting these sequelae remain limited.

This single-center randomized controlled clinical trial aims to evaluate the efficacy of a multimodal psychological intervention delivered remotely. The intervention combines digital cognitive training with a mindfulness-based stress reduction (MBSR) program adapted for pediatric populations.

Participants will be randomly assigned either to an immediate intervention group or to a waitlist control group. Within the intervention group, participants will be further allocated to one of two counterbalanced intervention sequences: (1) cognitive training followed by mindfulness or (2) mindfulness followed by cognitive training.

Assessments will include standardized neurocognitive tests administered in person, parent- and self-report questionnaires completed online via secure platforms, and electroencephalography (EEG) recordings to evaluate functional brain connectivity. Outcome measurements will be conducted at baseline, immediately following the intervention, and at a 6-month follow-up.

Вмешательства

• Поведенческое Digital cognitive training
  Adaptive exercises targeting attention, processing speed, memory and executive functions. Twelve-week intervention via Sincrolab online platform (4 practices per week, 15 minutes each), with a weekly online group session to encourage adherence.
• Поведенческое Online Mindfulness-Based Intervention
  Adapted Mindfulness-Based Stress Reduction (MBSR) program for children and adolescents. Twelve weekly online group sessions with guided home practice (4 practices, 15 minutes each) using audio materials.

Первичные конечные точки

• Symbol Digit Modalities Test (SDMT). [Срок оценки: Baseline]
• Continuous Performance Test, third edition (CPT-3) [Срок оценки: Baseline]
• Clinical Assessment of Memory (ECM) [Срок оценки: Baseline]
• Verbal Fluency Test (VFT) [Срок оценки: Baseline]
• Stroop. Test of Colors and Words. Revised edition. [Срок оценки: Baseline]
• Symbol Digit Modalities Test (SDMT) [Срок оценки: 6 months]
• Continuous Performance Test, third edition (CPT-3) [Срок оценки: 6 months]
• Clinical Assessment of Memory (ECM) [Срок оценки: 6 months]
• Stroop. Test of Colors and Words. Revised edition [Срок оценки: 6 months]
• Verbal Fluency Test (VFT) [Срок оценки: 6 months]

Вторичные конечные точки (12)

• Behavior Rating Inventory of Executive Function, second edition (BRIEF-2) [Срок оценки: Baseline]
• Behavior Assessment System for Children, third edition (BASC-3) [Срок оценки: Baseline]
• Brief Pain Inventory (BPI) [Срок оценки: Baseline]
• Adolescent Insomnia Questionnaire (AIQ) [Срок оценки: Baseline]
• Pediatric Sleep Disturbances Short Form (PROMIS) [Срок оценки: Baseline]
• Child and Adolescent Mindfulness Measure (CAMM). [Срок оценки: Baseline]
• Brain Functional Connectivity [Срок оценки: Baseline]
• Biomarkers [Срок оценки: Baseline]
• Behavior Assessment System for Children, third edition (BASC-3) [Срок оценки: 3 months]
• Brief Pain Inventory (BPI) [Срок оценки: 3 months]
• Adolescent Insomnia Questionnaire (AIQ) [Срок оценки: 3 months]
• Pediatric Sleep Disturbances Short Form (PROMIS) [Срок оценки: 3 months]

Критерии участия

Критерии включения

• Diagnosis of acute B-cell lymphoblastic leukemia.
• Previous treatment with CAR-T therapy, chemotherapy, and/or hematopoietic stem cell transplantation.
• Age between 8 and 18 years.
• Native Spanish speaker or high proficiency in Spanish sufficient to understand study procedures and complete assessment instruments.
• Access to a computer, tablet, or smartphone with an Internet connection.

Критерии исключения

• Diagnosis of intellectual disability, autism spectrum disorder, or acquired brain injury.
• Presence of uncontrolled or unstable medical or psychiatric conditions unrelated to leukemia.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Испания · 1 центр

• Hospital Universitario La Paz — Madrid

Публикации

• Ragoonanan D, Sheikh IN, Gupta S, Khazal SJ, Tewari P, Petropoulos D, Li S, Mahadeo KM. The Evolution of Chimeric Antigen Receptor T-Cell Therapy in Children, Adolescents and Young Adults with Acute Lymphoblastic Leukemia. Biomedicines. 2022 Sep 14;10(9):2286. doi: 10.3390/biomedicines10092286. PMID 36140387
• Caes L, Dick B, Duncan C, Allan J. The Cyclical Relation Between Chronic Pain, Executive Functioning, Emotional Regulation, and Self-Management. J Pediatr Psychol. 2021 Mar 18;46(3):286-292. doi: 10.1093/jpepsy/jsaa114. PMID 33249502
• Kamal M, Joseph J, Greenbaum U, Hicklen R, Kebriaei P, Srour SA, Wang XS. Patient-Reported Outcomes for Cancer Patients with Hematological Malignancies Undergoing Chimeric Antigen Receptor T Cell Therapy: A Systematic Review. Transplant Cell Ther. 2021 May;27(5):390.e1-390.e7. doi: 10.1016/j.jtct.2021.01.003. Epub 2021 Jan 7. PMID 33965176
• Ruark J, Mullane E, Cleary N, Cordeiro A, Bezerra ED, Wu V, Voutsinas J, Shaw BE, Flynn KE, Lee SJ, Turtle CJ, Maloney DG, Fann JR, Bar M. Patient-Reported Neuropsychiatric Outcomes of Long-Term Survivors after Chimeric Antigen Receptor T Cell Therapy. Biol Blood Marrow Transplant. 2020 Jan;26(1):34-43. doi: 10.1016/j.bbmt.2019.09.037. Epub 2019 Oct 9. PMID 31605820
• Thompson J, Fisher B, Sung L, Dvorak C, Dang H, Lo T, Alexander S. Musculoskeletal impairments in children receiving intensive therapy for acute leukemia or undergoing hematopoietic stem cell transplant: A report from the Children's Oncology Group. Pediatr Blood Cancer. 2021 Aug;68(8):e29053. doi: 10.1002/pbc.29053. Epub 2021 Apr 23. PMID 33890409
• Barata A, Hoogland AI, Kommalapati A, Logue J, Welniak T, Hyland KA, Eisel SL, Small BJ, Jayani RV, Booth-Jones M, Oswald LB, Gonzalez BD, Kirtane KS, Jain MD, Mokhtari S, Chavez JC, Lazaryan A, Shah BD, Locke FL, Jim HSL. Change in Patients' Perceived Cognition Following Chimeric Antigen Receptor T-Cell Therapy for Lymphoma. Transplant Cell Ther. 2022 Jul;28(7):401.e1-401.e7. doi: 10.1016/j.jtct. PMID 35580732
• Taylor MR, Steineck A, Lahijani S, Hall AG, Jim HSL, Phelan R, Knight JM. Biobehavioral Implications of Chimeric Antigen Receptor T-cell Therapy: Current State and Future Directions. Transplant Cell Ther. 2023 Jan;29(1):19-26. doi: 10.1016/j.jtct.2022.09.029. Epub 2022 Oct 5. PMID 36208728
• Shalabi H, Gust J, Taraseviciute A, Wolters PL, Leahy AB, Sandi C, Laetsch TW, Wiener L, Gardner RA, Nussenblatt V, Hill JA, Curran KJ, Olson TS, Annesley C, Wang HW, Khan J, Pasquini MC, Duncan CN, Grupp SA, Pulsipher MA, Shah NN. Beyond the storm - subacute toxicities and late effects in children receiving CAR T cells. Nat Rev Clin Oncol. 2021 Jun;18(6):363-378. doi: 10.1038/s41571-020-00456-y. PMID 33495553

Идентификаторы

NCT: NCT07479927 · PI23/00179 · 2023.832

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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