Acute Lymphoblastic Leukemia, PediatricNCT04400071
Biology and Benefits of Music Play and Stories for Kids/Parents During ALL Treatment
A study testing Active Music Engagement and Audio Storybooks in people with Acute Lymphoblastic Leukemia, Pediatric and Pediatric Cancer, run by Indiana University at 4 sites in United States.
Trial summary
Music therapy has become a standard palliative care service in many pediatric and adult hospitals; however, a majority of music therapy research has focused on the use of music to improve psychosocial dimensions of health, without considering biological dimensions. Read more about this study
- Who is it for?
- Ages 3 to 8 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Pediatric, Pediatric Cancer
- What is being tested?
- Active Music Engagement and Audio Storybooks
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 4 sitesUnited States
- Study dates
- 7 Aug 2020to 11 Apr 2025
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 8 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Child is 3 - 8 years of age at time of enrollment
- Child has diagnosis of standard or high risk B- or T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LyLy)
- Child is currently receiving induction therapy
- One parent (>18 years of age) can be present for all sessions.
Who cannot join
- Child has Ph+ ALL,
- Child has Cushing disease,
- Child is taking steroid medication for asthma and/or has asthma that is not well controlled,
- The parent does not speak English, or
- The child has a significant cognitive impairment that might hinder participation (determination made in consultation with attending physician, oncologist, and parents).
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Riley Hospital for Children
Indianapolis, Indiana, 46202
Children's Mercy Hospital
Kansas City, Missouri, 64108
UCSF Benioff Children's Hospital
Oakland, California, 94609
About this study
Official title: Biologic Mechanisms and Dosing of Active Music Engagement in Children With Acute Lymphoblastic Leukemia and Parents
Music therapy has become a standard palliative care service in many pediatric and adult hospitals; however, a majority of music therapy research has focused on the use of music to improve psychosocial dimensions of health, without considering biological dimensions. This study builds on prior work examining the psychosocial mechanisms of action underlying an Active Music Engagement (AME) intervention, designed to help manage emotional distress and improve positive health outcomes in young children with cancer and parents, by examining its effects on biomarkers of stress and immune function. The purposes of this two group, randomized controlled trial are to examine biological mechanisms of effect and dose-response relationships of AME on child/parent stress during the consolidation phase of Acute Lymphoblastic Leukemia (ALL) treatment. Specific aims are to: Aim 1. Establish whether AME lowers child and parent cortisol during ALL treatment. Aim 2. Examine cortisol as a mediator of AME effects on child and parent outcomes during ALL treatment. Aim 3 (exploratory). Examine the dose-response relationship of AME on child and parent cortisol during ALL treatment. Findings will provide a more holistic understanding about how active music interventions work to mitigate cancer-related stress and its potential to improve immune function, with direct implications for the evidence-based use of music to improve health.
Read the detailed description
Music therapy has become a standard palliative care service in many pediatric and adult hospitals. However, a majority of music therapy research has focused on the use of music to improve psychosocial dimensions of health, without considering biological dimensions. In addition, few studies have examined dose-response relationships. Cancer treatment is an inherently stressful experience, and a significant number of young children and parents (caregivers) experience persistent, interrelated emotional distress and poor quality of life. Many parents also experience traumatic stress symptoms because of their child's cancer diagnosis and treatment. The investigators previously tested an Active Music Engagement (AME) intervention that uses active music play to diminish stressful attributes of cancer treatment to help manage emotional/traumatic distress experienced by young children (ages 3-8) and parents and improve quality of life. A recent AME trial is examining psychosocial mechanisms of action responsible for change in child/parent outcomes. The current study expands on this work by examining AME's effects on several biomarkers to provide a more holistic understanding about how active music interventions work to mitigate cancer-related stress and its potential to improve immune function. The purposes of this two group, randomized controlled trial are to examine biological mechanisms of effect and dose-response relationships of AME on child/parent stress during the consolidation phase of Acute Lymphoblastic Leukemia (ALL) treatment. Specific aims are to: 1) establish whether AME lowers child and parent cortisol, 2) examine cortisol as a mediator of AME effects on child and parent outcomes, and 3) examine the dose-response relationship of AME on child and parent cortisol. Child/parent dyads (n=250) will be stratified (by age, site, ALL risk level) and randomized in blocks of four to AME or attention control. Each group will receive one 45-minute session during weekly clinic visits for the duration of ALL consolidation (4 weeks standard risk; 8 weeks high risk). Parents will complete measures at baseline and following the last study session. Child and parent salivary cortisol samples will be taken pre and post-session for the first 4 AME or attention control sessions. Child blood samples will be reserved from routine blood draws prior to sessions 1 and 4 (all participants) and session 8 (high risk participants). Linear mixed models will be used to estimate AME's effect on child and parent cortisol. Examining child and parent cortisol as mediators of AME effects on child and parent outcomes will be performed in an ANCOVA setting, fitting the appropriate mediation models using MPlus and then testing indirect effects using the percentile bootstrap approach to estimate the indirect effect. Graphical plots and non-linear repeated measures models will be used to examine the dose-response relationship of AME on child and parent cortisol.
- Being tested
- Active Music Engagement, Audio Storybooks
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Music EngagementBehavioural
Weekly 30-minute sessions with a board-certified music therapist delivered during weekly clinic visits for the consolidation phase of ALL treatment. Children with standard risk ALL will receive 4 sessions over 4 weeks. Children with high risk ALL will receive 8 sessions over 8 weeks. Sessions are delivered in a private setting during regularly scheduled clinic appointments. During the first visit, parent and child will receive information on how they can use music play activities to help manage distress during treatment. The music therapist will lead parent and child in a variety of music play activities. Parent and child will receive a music kit that includes items such as hand-held rhythm instruments, puppets, and a music CD. During subsequent visits the music therapist will lead parent and child through the music play activities, answer questions, and make suggestions for using these activities in the hospital and at home.
Audio StorybooksBehavioural
Weekly 30-minute sessions with a trained provider delivered during weekly clinic visits for the consolidation phase of ALL treatment. Children with standard risk ALL will receive 4 sessions over 4 weeks. Children with high risk ALL will receive 8 sessions over 8 weeks. Sessions are delivered in a private setting during regularly scheduled clinic appointments. Each session children/parents will choose and listen to one of three illustrated children's books with audio-recorded narration.
| Study group | Role | What they receive |
|---|---|---|
| Active Music Engagement | Experimental | See intervention description. Receives: Behavioral: Active Music Engagement |
| Audio Storybooks | Active comparator | See intervention description. Receives: Behavioral: Audio Storybooks |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Child Stress (Salivary Cortisol)
The primary outcome will be the percent change in child salivary cortisol from pre- to post-session at each session number (2, 3 and 4) for each child. This outcome will be calculated as 100*ln(post/pre) to represent the percentage change in cortisol levels (ln=natural logarithm function). Negative values will indicate a reduction in cortisol relative to the pre-session value. Investigators will use a linear mixed effects model for repeated measures to examine change in the cortisol levels over time with child as a subject effect. Predictors will include session number (2, 3, 4), intervention group (AME vs Storybooks) and patient risk level (High vs Standard). A variety of covariance structures will be examined and one will be chosen exhibiting the smallest Akaike's Information Criterion (AIC) value.
Measured: Pre/Post-Sessions 2, 3, and 4 (each session is 7 days apart; each session has a 30 min. duration).
Percent Change in Parent Stress (Salivary Cortisol)
The primary outcome will be the percent change in parent salivary cortisol from pre- to post-session at each session number (1, 2, 3 and 4) for each parent. This outcome will be calculated as 100*ln(post/pre) to represent the percentage change in cortisol levels (ln=natural logarithm function). Negative values will indicate a reduction in cortisol relative to the pre-session value. Investigators will use a linear mixed effects model for repeated measures to examine change in the cortisol levels over time with parent as a subject effect. Predictors will include session number (1, 2, 3, 4), intervention group (AME vs Storybooks) and patient risk level (High vs Standard). A variety of covariance structures will be examined and one will be chosen exhibiting the smallest Akaike's Information Criterion (AIC) value.
Measured: Pre/Post-Sessions 1, 2, 3, and 4 (each session is 7 days apart; each session has a 30 min. duration).
Change in Child Immune Function - IL-10 Cytokine
IL-10 is a cytokine broadly produced by many cells in the immune system. It is a feedback regulator known to limit inflammatory responses. IL-10 was measured using the BioRad BioPlex Human 7-plex assay. This assay uses antibodies to detect and quantify cytokine levels. Most assay values were below the limit of detection (LOD). For all participants with values below the LOD, the lowest non-zero calibrator (6.9 pg/mL) was assigned.
Measured: Pre-session 1 (all children); Pre-Session 4 (all children); Pre-Session 8 (high risk children only)
Change in Child Immune Function - IL-13 Cytokine
IL-13 is a cytokine that helps drive type 2 responses allowing the body to defend against parasites by activating mast cells, basophils, and eosinophils. IL-13 was measured using the BioRad BioPlex Human 7-plex assay. This assay uses antibodies to detect and quantify cytokine levels. Most assay values were below the limit of detection (LOD). For all participants with values below the LOD, the lowest non-zero calibrator (1.9 pg/mL) was assigned.
Measured: Pre-session 1 (all children); Pre-Session 4 (all children); Pre-Session 8 (high risk children only)
Change in Child Immune Function - IL-6 Cytokine
IL- 6 is a pro-inflammatory cytokine that activates the JAK/STAT pathway. IL-6 is part of defense against infections; however, overproduction can lead to severe complications. IL-6 was measured using the BioRad BioPlex Human 7-plex assay. This assay uses antibodies to detect and quantify cytokine levels. Most assay values were below the limit of detection (LOD). For all participants with values below the LOD, the lowest non-zero calibrator (1.4 pg/mL) was assigned.
Measured: Pre-session 1 (all children); Pre-Session 4 (all children); Pre-Session 8 (high risk children only)
Change in Child Immune Function - TNF-α Cytokine
TNF-α is a pro-inflammatory cytokine known activate innate and adaptive immune responses. The chemical signals from TNF will affect the body's response to infection. TNF-α was measured using the BioRad BioPlex Human 7-plex assay. This assay uses antibodies to detect and quantify cytokine levels. Most assay values were below the limit of detection (LOD). For all participants with values below the LOD, the lowest non-zero calibrator (26.7 pg/mL) was assigned.
Measured: Pre-session 1 (all children); Pre-Session 4 (all children); Pre-Session 8 (high risk children only)
Percent Change in Salivary Cortisol and Child Health Questionnaire-Mental Health Subscale (CHQ)
Using Mplus software, investigators will conduct a parallel mediation analysis within a structural equation modeling (SEM) framework to evaluate the mechanisms of the intervention. The model will simultaneously test two indirect effects (a*b): (1) the intervention's impact on child mental health through percent change in child cortisol, and (2) the impact through percent change in parent cortisol. CHQ mental health scores range from 16 - 80 with higher scores indicating better mental health. Mediators will be calculated as an average of pre to post session change in salivary cortisol across sessions for both children and parents. The model will be adjusted for patient risk level (high vs. standard), age, study site and baseline version of outcome as covariates. Percentile bootstrap approach (5,000 resamples) will be used to generate 95% confidence intervals. Missing data will be handled via Full Information Maximum Likelihood (FIML) to ensure robust parameter estimation.
Measured: Baseline; Follow-up Post-Session Week 4 (standard risk participants); Follow-up Post-Session Week 8 (high risk participants)
Percent Change in Salivary Cortisol and KINDLR Questionnaire for Measuring Health-Related Quality of Life in Children
Using Mplus software, investigators will conduct a parallel mediation analysis within a structural equation modeling (SEM) framework to evaluate the mechanisms of the intervention. The model will simultaneously test two indirect effects (a*b): (1) the intervention's impact on child quality of life through percent change in child cortisol, and (2) the impact through percent change in parent cortisol. KINDLR quality of life scores range from 20 - 100 with higher scores indicating better quality of life. Mediators will be calculated as an average of pre to post session change in salivary cortisol across sessions for both children and parents. The model will be adjusted for patient risk level (high vs. standard), age, study site and baseline version of outcome as covariates. Percentile bootstrap approach (5,000 resamples) will be used to generate 95% confidence intervals. Missing data will be handled via Full Information Maximum Likelihood (FIML) to ensure robust parameter estimation.
Measured: Baseline; Follow-up Post-Session Week 4 (standard risk participants); Follow-up Post-Session Week 8 (high risk participants)
Percent Change in Salivary Cortisol and Profile of Mood States - Short Form (POMS-SF)
Using Mplus software, investigators will conduct a parallel mediation analysis within a structural equation modeling (SEM) framework to evaluate the mechanisms of the intervention. The model will simultaneously test two indirect effects (a*b): (1) the intervention's impact on child's mood disturbance through percent change in child cortisol, and (2) the impact through percent change in parent cortisol. POMS-SF scores range from -32-116 with higher scores indicating greater mood disturbance. Mediators will be calculated as an average of pre to post session change in salivary cortisol across sessions for both children and parents. The model will be adjusted for patient risk level (high vs. standard), age, study site and baseline version of outcome as covariates. Percentile bootstrap approach (5,000 resamples) will be used to generate 95% confidence intervals. Missing data will be handled via Full Information Maximum Likelihood (FIML) to ensure robust parameter estimation.
Measured: Baseline; Follow-up Post-Session Week 4 (standard risk participants); Follow-up Post-Session Week 8 (high risk participants)
Percent Change in Salivary Cortisol and Impact of Events Scale - Revised (IES-R)
Using Mplus software, investigators will conduct a parallel mediation analysis within a structural equation modeling (SEM) framework to evaluate the mechanisms of the intervention. The model will simultaneously test two indirect effects (a*b): (1) the intervention's impact on child's traumatic stress symptoms through percent change in child cortisol, and (2) the impact through percent change in parent cortisol. IES-R scores range from 0-12 with higher scores indicating greater traumatic stress symptoms. Mediators will be calculated as an average of pre to post session change in salivary cortisol across sessions for both children and parents. The model will be adjusted for patient risk level (high vs. standard), age, study site and baseline version of outcome as covariates. Percentile bootstrap approach (5,000 resamples) will be used to generate 95% confidence intervals. Missing data will be handled via Full Information Maximum Likelihood (FIML) to ensure robust parameter estimation.
Measured: Baseline; Follow-up Post-Session Week 4 (standard risk participants); Follow-up Post-Session Week 8 (high risk participants)
Percent Change in Salivary Cortisol and Index of Well-being
Using Mplus software, investigators will conduct a parallel mediation analysis within a structural equation modeling (SEM) framework to evaluate the mechanisms of the intervention. The model will simultaneously test two indirect effects (a*b): (1) the intervention's impact on child's well-being through percent change in child cortisol, and (2) the impact through percent change in parent cortisol. IWB scores range from 9-63 with higher scores indicating greater well-being. Mediators will be calculated as an average of pre to post session change in salivary cortisol across sessions for both children and parents. The model will be adjusted for patient risk level (high vs. standard), age, study site and baseline version of outcome as covariates. Percentile bootstrap approach (5,000 resamples) will be used to generate 95% confidence intervals. Missing data will be handled via Full Information Maximum Likelihood (FIML) to ensure robust parameter estimation.
Measured: Baseline; Follow-up Post-Session Week 4 (standard risk participants); Follow-up Post-Session Week 8 (high risk participants)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2020
- Study start7 Aug 2020
- Primary completion11 Apr 2025
- Study completion11 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic Leukemia, PediatricStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Mercy Hospital Kansas City, Ann & Robert H Lurie Children's Hospital of Chicago, National Institute of Nursing Research (NINR), James Whitcomb Riley Hospital for Children, UCSF Benioff Children's Hospital Oakland
- Responsible party
- Principal investigator, Sheri Robb, Indiana University
- Investigators
- Sheri L Robb, PhD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04400071
- Sponsor's protocol ID
- R01NR019190
- Other IDs
- 5R01NR019190-05
- Status last verified
- Oct 2026
- First submitted
- 15 May 2020
- Last updated
- 28 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Robb SL, Clair AA, Watanabe M, Monahan PO, Azzouz F, Stouffer JW, Ebberts A, Darsie E, Whitmer C, Walker J, Nelson K, Hanson-Abromeit D, Lane D, Hannan A. A non-randomized [corrected] controlled trial of the active music engagement (AME) intervention on children with cancer. Psychooncology. 2008 Jul;17(7):699-708. doi: 10.1002/pon.1301.
PubMed 18033724Robb SL, Haase JE, Perkins SM, Haut PR, Henley AK, Knafl KA, Tong Y. Pilot Randomized Trial of Active Music Engagement Intervention Parent Delivery for Young Children With Cancer. J Pediatr Psychol. 2017 Mar 1;42(2):208-219. doi: 10.1093/jpepsy/jsw050.
PubMed 27289068Robb SL. The effect of therapeutic music interventions on the behavior of hospitalized children in isolation: developing a contextual support model of music therapy. J Music Ther. 2000 Summer;37(2):118-46. doi: 10.1093/jmt/37.2.118.
PubMed 10932125MacLean JA, Stegenga KA, Henley AK, Robb SL. Implementing NIH Behavior Change Consortium Treatment Fidelity Recommendations in a Multi-Site Randomized Controlled Trial of an Active Music Engagement Intervention for Young Children with Cancer and Parents. Integr Cancer Ther. 2022 Jan-Dec;21:15347354221140491. doi: 10.1177/15347354221140491.
PubMed 36510388Robb SL, Russ KA, Holochwost SJ, Stegenga K, Perkins SM, Jacob SA, Henley AK, MacLean JA. Protocol and biomarker strategy for a multi-site randomized controlled trial examining biological mechanisms and dosing of active music engagement in children with acute lymphoblastic leukemia and lymphoma and parents. BMC Complement Med Ther. 2023 Mar 27;23(1):90. doi: 10.1186/s12906-023-03909-w.
PubMed 36973774Holochwost SJ, Harman E, Stegenga K, Jacob SA, Robb SL. Who benefits from active music engagement during cancer treatment? Associations of sociodemographic characteristics and risk factors with moderators of intervention effects. Front Psychol. 2025 Jul 29;16:1550051. doi: 10.3389/fpsyg.2025.1550051. eCollection 2025.
PubMed 40799339
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biologic Mechanisms and Dosing of Active Music Engagement in Children With Acute Lymphoblastic Leukemia and Parents
- ClinicalTrials.gov ID
- NCT04400071
- Acronym / sponsor ID
- R01NR019190
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- Children's Mercy Hospital Kansas City, Ann & Robert H Lurie Children's Hospital of Chicago, National Institute of Nursing Research (NINR), James Whitcomb Riley Hospital for Children, UCSF Benioff Children's Hospital Oakland
- Study start
- 7 Aug 2020 (actual)
- Primary completion
- 11 Apr 2025 (actual)
- Study completion
- 11 Apr 2025 (actual)
- First posted
- 22 May 2020 (actual)
- Results
- Posted 28 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Music therapy has become a standard palliative care service in many pediatric and adult hospitals; however, a majority of music therapy research has focused on the use of music to improve psychosocial dimensions of health, without considering biological dimensions. This study builds on prior work examining the psychosocial mechanisms of action underlying an Active Music Engagement (AME) intervention, designed to help manage emotional distress and improve positive health outcomes in young children with cancer and parents, by examining its effects on biomarkers of stress and immune function. The purposes of this two group, randomized controlled trial are to examine biological mechanisms of effect and dose-response relationships of AME on child/parent stress during the consolidation phase of Acute Lymphoblastic Leukemia (ALL) treatment. Specific aims are to: Aim 1. Establish whether AME lowers child and parent cortisol during ALL treatment. Aim 2. Examine cortisol as a mediator of AME effects on child and parent outcomes during ALL treatment. Aim 3 (exploratory). Examine the dose-response relationship of AME on child and parent cortisol during ALL treatment. Findings will provide a more holistic understanding about how active music interventions work to mitigate cancer-related stress and its potential to improve immune function, with direct implications for the evidence-based use of music to improve health.
Detailed description
Music therapy has become a standard palliative care service in many pediatric and adult hospitals. However, a majority of music therapy research has focused on the use of music to improve psychosocial dimensions of health, without considering biological dimensions. In addition, few studies have examined dose-response relationships. Cancer treatment is an inherently stressful experience, and a significant number of young children and parents (caregivers) experience persistent, interrelated emotional distress and poor quality of life. Many parents also experience traumatic stress symptoms because of their child's cancer diagnosis and treatment. The investigators previously tested an Active Music Engagement (AME) intervention that uses active music play to diminish stressful attributes of cancer treatment to help manage emotional/traumatic distress experienced by young children (ages 3-8) and parents and improve quality of life. A recent AME trial is examining psychosocial mechanisms of action responsible for change in child/parent outcomes. The current study expands on this work by examining AME's effects on several biomarkers to provide a more holistic understanding about how active music interventions work to mitigate cancer-related stress and its potential to improve immune function. The purposes of this two group, randomized controlled trial are to examine biological mechanisms of effect and dose-response relationships of AME on child/parent stress during the consolidation phase of Acute Lymphoblastic Leukemia (ALL) treatment. Specific aims are to: 1) establish whether AME lowers child and parent cortisol, 2) examine cortisol as a mediator of AME effects on child and parent outcomes, and 3) examine the dose-response relationship of AME on child and parent cortisol. Child/parent dyads (n=250) will be stratified (by age, site, ALL risk level) and randomized in blocks of four to AME or attention control. Each group will receive one 45-minute session during weekly clinic visits for the duration of ALL consolidation (4 weeks standard risk; 8 weeks high risk). Parents will complete measures at baseline and following the last study session. Child and parent salivary cortisol samples will be taken pre and post-session for the first 4 AME or attention control sessions. Child blood samples will be reserved from routine blood draws prior to sessions 1 and 4 (all participants) and session 8 (high risk participants). Linear mixed models will be used to estimate AME's effect on child and parent cortisol. Examining child and parent cortisol as mediators of AME effects on child and parent outcomes will be performed in an ANCOVA setting, fitting the appropriate mediation models using MPlus and then testing indirect effects using the percentile bootstrap approach to estimate the indirect effect. Graphical plots and non-linear repeated measures models will be used to examine the dose-response relationship of AME on child and parent cortisol.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Music Engagement | Experimental | Behavioral: Active Music EngagementSee intervention description. |
| Audio Storybooks | Active comparator | Behavioral: Audio StorybooksSee intervention description. |
Who may qualify
- Ages
- 3 to 8 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Child is 3 - 8 years of age at time of enrollment
- Child has diagnosis of standard or high risk B- or T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LyLy)
- Child is currently receiving induction therapy
- One parent (>18 years of age) can be present for all sessions.
Key exclusion criteria (5 listed)
- Child has Ph+ ALL,
- Child has Cushing disease,
- Child is taking steroid medication for asthma and/or has asthma that is not well controlled,
- The parent does not speak English, or
- The child has a significant cognitive impairment that might hinder participation (determination made in consultation with attending physician, oncologist, and parents).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Music EngagementWeekly 30-minute sessions with a board-certified music therapist delivered during weekly clinic visits for the consolidation phase of ALL treatment. Children with standard risk ALL will receive 4 sessions over 4 weeks. Children with high risk ALL will receive 8 sessions over 8 weeks. Sessions are delivered in a private setting during regularly scheduled clinic appointments. During the first visit, parent and child will receive information on how they can use music play activities to help manage distress during treatment. The music therapist will lead parent and child in a variety of music play activities. Parent and child will receive a music kit that includes items such as hand-held rhythm instruments, puppets, and a music CD. During subsequent visits the music therapist will lead parent and child through the music play activities, answer questions, and make suggestions for using these activities in the hospital and at home. | Behavioural | Active Music Engagement |
| Audio StorybooksWeekly 30-minute sessions with a trained provider delivered during weekly clinic visits for the consolidation phase of ALL treatment. Children with standard risk ALL will receive 4 sessions over 4 weeks. Children with high risk ALL will receive 8 sessions over 8 weeks. Sessions are delivered in a private setting during regularly scheduled clinic appointments. Each session children/parents will choose and listen to one of three illustrated children's books with audio-recorded narration. | Behavioural | Audio Storybooks |
Primary outcome
Percent Change in Child Stress (Salivary Cortisol)
Time frame: Pre/Post-Sessions 2, 3, and 4 (each session is 7 days apart; each session has a 30 min. duration).
The primary outcome will be the percent change in child salivary cortisol from pre- to post-session at each session number (2, 3 and 4) for each child. This outcome will be calculated as 100*ln(post/pre) to represent the percentage change in cortisol levels (ln=natural logarithm function). Negative values will indicate a reduction in cortisol relative to the pre-session value. Investigators will use a linear mixed effects model for repeated measures to examine change in the cortisol levels over time with child as a subject effect. Predictors will include session number (2, 3, 4), intervention group (AME vs Storybooks) and patient risk level (High vs Standard). A variety of covariance structures will be examined and one will be chosen exhibiting the smallest Akaike's Information Criterion (AIC) value.
Percent Change in Parent Stress (Salivary Cortisol)
Time frame: Pre/Post-Sessions 1, 2, 3, and 4 (each session is 7 days apart; each session has a 30 min. duration).
The primary outcome will be the percent change in parent salivary cortisol from pre- to post-session at each session number (1, 2, 3 and 4) for each parent. This outcome will be calculated as 100*ln(post/pre) to represent the percentage change in cortisol levels (ln=natural logarithm function). Negative values will indicate a reduction in cortisol relative to the pre-session value. Investigators will use a linear mixed effects model for repeated measures to examine change in the cortisol levels over time with parent as a subject effect. Predictors will include session number (1, 2, 3, 4), intervention group (AME vs Storybooks) and patient risk level (High vs Standard). A variety of covariance structures will be examined and one will be chosen exhibiting the smallest Akaike's Information Criterion (AIC) value.
Change in Child Immune Function - IL-10 Cytokine
Time frame: Pre-session 1 (all children); Pre-Session 4 (all children); Pre-Session 8 (high risk children only)
IL-10 is a cytokine broadly produced by many cells in the immune system. It is a feedback regulator known to limit inflammatory responses. IL-10 was measured using the BioRad BioPlex Human 7-plex assay. This assay uses antibodies to detect and quantify cytokine levels. Most assay values were below the limit of detection (LOD). For all participants with values below the LOD, the lowest non-zero calibrator (6.9 pg/mL) was assigned.
Change in Child Immune Function - IL-13 Cytokine
Time frame: Pre-session 1 (all children); Pre-Session 4 (all children); Pre-Session 8 (high risk children only)
IL-13 is a cytokine that helps drive type 2 responses allowing the body to defend against parasites by activating mast cells, basophils, and eosinophils. IL-13 was measured using the BioRad BioPlex Human 7-plex assay. This assay uses antibodies to detect and quantify cytokine levels. Most assay values were below the limit of detection (LOD). For all participants with values below the LOD, the lowest non-zero calibrator (1.9 pg/mL) was assigned.
Change in Child Immune Function - IL-6 Cytokine
Time frame: Pre-session 1 (all children); Pre-Session 4 (all children); Pre-Session 8 (high risk children only)
IL- 6 is a pro-inflammatory cytokine that activates the JAK/STAT pathway. IL-6 is part of defense against infections; however, overproduction can lead to severe complications. IL-6 was measured using the BioRad BioPlex Human 7-plex assay. This assay uses antibodies to detect and quantify cytokine levels. Most assay values were below the limit of detection (LOD). For all participants with values below the LOD, the lowest non-zero calibrator (1.4 pg/mL) was assigned.
Change in Child Immune Function - TNF-α Cytokine
Time frame: Pre-session 1 (all children); Pre-Session 4 (all children); Pre-Session 8 (high risk children only)
TNF-α is a pro-inflammatory cytokine known activate innate and adaptive immune responses. The chemical signals from TNF will affect the body's response to infection. TNF-α was measured using the BioRad BioPlex Human 7-plex assay. This assay uses antibodies to detect and quantify cytokine levels. Most assay values were below the limit of detection (LOD). For all participants with values below the LOD, the lowest non-zero calibrator (26.7 pg/mL) was assigned.
Percent Change in Salivary Cortisol and Child Health Questionnaire-Mental Health Subscale (CHQ)
Time frame: Baseline; Follow-up Post-Session Week 4 (standard risk participants); Follow-up Post-Session Week 8 (high risk participants)
Using Mplus software, investigators will conduct a parallel mediation analysis within a structural equation modeling (SEM) framework to evaluate the mechanisms of the intervention. The model will simultaneously test two indirect effects (a*b): (1) the intervention's impact on child mental health through percent change in child cortisol, and (2) the impact through percent change in parent cortisol. CHQ mental health scores range from 16 - 80 with higher scores indicating better mental health. Mediators will be calculated as an average of pre to post session change in salivary cortisol across sessions for both children and parents. The model will be adjusted for patient risk level (high vs. standard), age, study site and baseline version of outcome as covariates. Percentile bootstrap approach (5,000 resamples) will be used to generate 95% confidence intervals. Missing data will be handled via Full Information Maximum Likelihood (FIML) to ensure robust parameter estimation.
Percent Change in Salivary Cortisol and KINDLR Questionnaire for Measuring Health-Related Quality of Life in Children
Time frame: Baseline; Follow-up Post-Session Week 4 (standard risk participants); Follow-up Post-Session Week 8 (high risk participants)
Using Mplus software, investigators will conduct a parallel mediation analysis within a structural equation modeling (SEM) framework to evaluate the mechanisms of the intervention. The model will simultaneously test two indirect effects (a*b): (1) the intervention's impact on child quality of life through percent change in child cortisol, and (2) the impact through percent change in parent cortisol. KINDLR quality of life scores range from 20 - 100 with higher scores indicating better quality of life. Mediators will be calculated as an average of pre to post session change in salivary cortisol across sessions for both children and parents. The model will be adjusted for patient risk level (high vs. standard), age, study site and baseline version of outcome as covariates. Percentile bootstrap approach (5,000 resamples) will be used to generate 95% confidence intervals. Missing data will be handled via Full Information Maximum Likelihood (FIML) to ensure robust parameter estimation.
Percent Change in Salivary Cortisol and Profile of Mood States - Short Form (POMS-SF)
Time frame: Baseline; Follow-up Post-Session Week 4 (standard risk participants); Follow-up Post-Session Week 8 (high risk participants)
Using Mplus software, investigators will conduct a parallel mediation analysis within a structural equation modeling (SEM) framework to evaluate the mechanisms of the intervention. The model will simultaneously test two indirect effects (a*b): (1) the intervention's impact on child's mood disturbance through percent change in child cortisol, and (2) the impact through percent change in parent cortisol. POMS-SF scores range from -32-116 with higher scores indicating greater mood disturbance. Mediators will be calculated as an average of pre to post session change in salivary cortisol across sessions for both children and parents. The model will be adjusted for patient risk level (high vs. standard), age, study site and baseline version of outcome as covariates. Percentile bootstrap approach (5,000 resamples) will be used to generate 95% confidence intervals. Missing data will be handled via Full Information Maximum Likelihood (FIML) to ensure robust parameter estimation.
Percent Change in Salivary Cortisol and Impact of Events Scale - Revised (IES-R)
Time frame: Baseline; Follow-up Post-Session Week 4 (standard risk participants); Follow-up Post-Session Week 8 (high risk participants)
Using Mplus software, investigators will conduct a parallel mediation analysis within a structural equation modeling (SEM) framework to evaluate the mechanisms of the intervention. The model will simultaneously test two indirect effects (a*b): (1) the intervention's impact on child's traumatic stress symptoms through percent change in child cortisol, and (2) the impact through percent change in parent cortisol. IES-R scores range from 0-12 with higher scores indicating greater traumatic stress symptoms. Mediators will be calculated as an average of pre to post session change in salivary cortisol across sessions for both children and parents. The model will be adjusted for patient risk level (high vs. standard), age, study site and baseline version of outcome as covariates. Percentile bootstrap approach (5,000 resamples) will be used to generate 95% confidence intervals. Missing data will be handled via Full Information Maximum Likelihood (FIML) to ensure robust parameter estimation.
Percent Change in Salivary Cortisol and Index of Well-being
Time frame: Baseline; Follow-up Post-Session Week 4 (standard risk participants); Follow-up Post-Session Week 8 (high risk participants)
Using Mplus software, investigators will conduct a parallel mediation analysis within a structural equation modeling (SEM) framework to evaluate the mechanisms of the intervention. The model will simultaneously test two indirect effects (a*b): (1) the intervention's impact on child's well-being through percent change in child cortisol, and (2) the impact through percent change in parent cortisol. IWB scores range from 9-63 with higher scores indicating greater well-being. Mediators will be calculated as an average of pre to post session change in salivary cortisol across sessions for both children and parents. The model will be adjusted for patient risk level (high vs. standard), age, study site and baseline version of outcome as covariates. Percentile bootstrap approach (5,000 resamples) will be used to generate 95% confidence intervals. Missing data will be handled via Full Information Maximum Likelihood (FIML) to ensure robust parameter estimation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18033724Robb SL, Clair AA, Watanabe M, Monahan PO, Azzouz F, Stouffer JW, Ebberts A, Darsie E, Whitmer C, Walker J, Nelson K, Hanson-Abromeit D, Lane D, Hannan A. A non-randomized [corrected] controlled trial of the active music engagement (AME) intervention on children with cancer. Psychooncology. 2008 Jul;17(7):699-708. doi: 10.1002/pon.1301.
- Background: PubMed 27289068Robb SL, Haase JE, Perkins SM, Haut PR, Henley AK, Knafl KA, Tong Y. Pilot Randomized Trial of Active Music Engagement Intervention Parent Delivery for Young Children With Cancer. J Pediatr Psychol. 2017 Mar 1;42(2):208-219. doi: 10.1093/jpepsy/jsw050.
- Background: PubMed 10932125Robb SL. The effect of therapeutic music interventions on the behavior of hospitalized children in isolation: developing a contextual support model of music therapy. J Music Ther. 2000 Summer;37(2):118-46. doi: 10.1093/jmt/37.2.118.
- Background: PubMed 36510388MacLean JA, Stegenga KA, Henley AK, Robb SL. Implementing NIH Behavior Change Consortium Treatment Fidelity Recommendations in a Multi-Site Randomized Controlled Trial of an Active Music Engagement Intervention for Young Children with Cancer and Parents. Integr Cancer Ther. 2022 Jan-Dec;21:15347354221140491. doi: 10.1177/15347354221140491.
- Background: PubMed 36973774Robb SL, Russ KA, Holochwost SJ, Stegenga K, Perkins SM, Jacob SA, Henley AK, MacLean JA. Protocol and biomarker strategy for a multi-site randomized controlled trial examining biological mechanisms and dosing of active music engagement in children with acute lymphoblastic leukemia and lymphoma and parents. BMC Complement Med Ther. 2023 Mar 27;23(1):90. doi: 10.1186/s12906-023-03909-w.
- Background: PubMed 40799339Holochwost SJ, Harman E, Stegenga K, Jacob SA, Robb SL. Who benefits from active music engagement during cancer treatment? Associations of sociodemographic characteristics and risk factors with moderators of intervention effects. Front Psychol. 2025 Jul 29;16:1550051. doi: 10.3389/fpsyg.2025.1550051. eCollection 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sheri L Robb, PhD principal investigator
Indiana University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Music Engagement and Audio Storybooks in people with Acute Lymphoblastic Leukemia, Pediatric and Pediatric Cancer, run by Indiana University at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Child Stress (Salivary Cortisol) (time frame: Pre/Post-Sessions 2, 3, and 4 (each session is 7 days apart; each session has a 30 min. duration).). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04400071, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.