Acute Lymphoblastic Leukemia
Conditions
Keywords
Acute lymphoblastic leukemia, CAR T-cell therapy, Pediatric oncology, Neuropsychology, Mindfulness, Biopsychosocial outcomes
Brief summary
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.
Detailed description
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.
Interventions
BEHAVIORALDigital 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.
BEHAVIORALOnline 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.
Sponsors
Hospital Universitario La Paz
Instituto de Investigación Hospital Universitario La Paz
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized block design (based on the BRIEF-2 Emotional Regulation Index score), waitlist control group and counterbalanced intervention sequences.
Eligibility
Sex/Gender
ALL
Age
8 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* Diagnosis of intellectual disability, autism spectrum disorder, or acquired brain injury. * Presence of uncontrolled or unstable medical or psychiatric conditions unrelated to leukemia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symbol Digit Modalities Test (SDMT). | Baseline | It assesses processing speed based on the total number of items completed in 90 seconds. Scores range from 0 to a maximum determined by the speed of task completion. Higher scores indicate better processing speed. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Continuous Performance Test, third edition (CPT-3) | Baseline | It assesses sustained visual attention, impulsivity, and vigilance through continuous performance tasks that require responses to target stimuli and inhibition of non-target stimuli. Outcome measures include omission errors, commission errors, reaction time, and variability, which are expressed as standardized T-scores. Higher T-scores indicate poorer performance. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Clinical Assessment of Memory (ECM) | Baseline | It assesses working memory and immediate memory in auditory-verbal and visuospatial modalities. Scores are expressed as standardized scores based on Spanish norms. Higher scores indicate better memory performance. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Verbal Fluency Test (VFT) | Baseline | Assesses linguistic and executive functions, including phonological and semantic fluency. The score is the total number of correct words generated in 60 seconds. Higher scores indicate better performance. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Stroop. Test of Colors and Words. Revised edition. | Baseline | It measures attention and executive functioning, specifically the ability to inhibit automatic responses and resist interference from established behavior patterns. Scores are based on the number of correct responses completed in 45 seconds, depending on the condition. Higher scores indicate better executive functioning. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Symbol Digit Modalities Test (SDMT) | 6 months | It assesses processing speed based on the total number of items completed in 90 seconds. Scores range from 0 to a maximum determined by the speed of task completion. Higher scores indicate better processing speed. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Stroop. Test of Colors and Words. Revised edition | 6 months | It measures attention and executive functioning, specifically the ability to inhibit automatic responses and resist interference from established behavior patterns. Scores are based on the number of correct responses completed in 45 seconds, depending on the condition. Higher scores indicate better executive functioning. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Behavior Rating Inventory of Executive Function, second edition (BRIEF-2) | Baseline | 63-item questionnaire that assesses the patient's executive functions (completed by parents). Higher scores in each domain indicate a worse outcome. Spanish norms in T scores (mean = 50; standard deviation = 10). The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Behavior Assessment System for Children, third edition (BASC-3) | Baseline | It measures patients' emotional and behavioral problems, both in the version completed by the patient's legal guardians and in the self-assessment carried out by the patient themselves. It is a report of 139 items, scored on a 4-point Likert frequency scale. High scores indicate problematic levels of functioning. Scores are reported as T-scores (mean = 50; standard deviation = 10). The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Brief Pain Inventory (BPI) | Baseline | This 10-question questionnaire includes questions (from 0 to 10, referring to the last 7 days) covering two dimensions: pain intensity (the most intense and mildest pain of the week, average pain, and current pain) and pain interference (in general activity, mood, walking, school, sleep, and enjoyment of life). Higher scores on a Likert scale of 0 to 10 indicate more pain. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Adolescent Insomnia Questionnaire (AIQ) | Baseline | This is a 13-item questionnaire, the original version of which is in English. In this study, the questionnaire will be adapted and validated in Spanish. Higher scores on a Likert scale of 0 to 4 indicate greater insomnia. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Pediatric Sleep Disturbances Short Form (PROMIS) | Baseline | A 4-question questionnaire that assesses problems falling asleep and staying asleep over the past 7 days. Higher scores on a Likert scale of 1 to 5 indicate poorer sleep. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Child and Adolescent Mindfulness Measure (CAMM). | Baseline | Assesses mindfulness skills related to present moment awareness and nonjudgmental acceptance. Total scores range from 0 to 40. Higher scores indicate greater mindfulness ability. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
| Brain Functional Connectivity | Baseline | EEG-based measures including spectral power, frequency analysis, functional connectivity indices, and graph theory metrics. |
| Biomarkers | Baseline | White blood cells, platelets, and C-reactive protein. |
| Child and Adolescent Mindfulness Measure (CAMM) | 3 months | Assesses mindfulness skills related to present moment awareness and nonjudgmental acceptance. Total scores range from 0 to 40. Higher scores indicate greater mindfulness ability. The scores will be converted to z-scores (mean = 0; standard deviation = 1) to equate and compare the values of instruments with different units of measurement. |
Countries
Spain
Contacts
CONTACTEduardo Fernandez Jimenes, Phd
Outcome results
None listed