Physical Activity and Exercise During Early Treatment Phases for Childhood Acute Lymphoblastic Leukaemia to Protect Against Muscle Loss and Improve Frailty Outcomes (PROTECT)

The PROTECT Trial Physical Activity and Exercise During Early Treatment for Children With Acute Lymphoblastic Leukaemia to Protect Against Sarcopenia and Improve Frailty Outcomes: a Pilot Randomised Controlled Trial

This is a small trial testing out a new approach before doing a bigger study. Researchers are observing a group of children/adolescents (ages 5-17) with acute lymphoblastic leukemia (ALL) and testing a physical activity and exercise program on a group of them who after 5 weeks of treatment show signs of weakness or frailty.

Kids who are NOT losing muscle aren't part of the exercise trial - they're just monitored over time to see how they do.

The goal:

To see if an exercise program helps kids who are getting weaker from acute lymphoblastic leukemia treatment build back/maintain their strength, compared to kids who don't do the extra intervention. The study will also look at if this way of measuring muscle weakness works well for kids with cancer.

Study Overview

• Status: Recruiting
• Conditions: Sarcopenia; Acute Lymphoblastic Leukemia
• Intervention / Treatment: Behavioral: Exercise

Detailed Description

This is a pilot randomised controlled trial with a hybrid implementation design. In this pilot study, we are exploring a range of outcome measures to assess feasibility, acceptability, and preliminary variability. Data from these measures will inform the selection of the most appropriate primary and secondary outcomes, and estimate sample size for a future definitive trial. At 5 weeks following an acute lymphoblastic leukaemia diagnosis children/adolescents (5-17 years) will be assessed for frailty using a novel frailty framework, to evaluate their frailty risk and identify those with signs of sarcopenia. Children with signs of sarcopenia will be randomised to one of two groups: 1. Standard care only, or,2. Physical activity and strengthening intervention plus activity tracking with a Fitbit (A wearable electronic activity tracker). This study will evaluate if the implementability of this intervention as well as the limited efficacy and investigate the framework for frailty used in this study. It is known that children undergoing acute treatment for ALL experience signs of frailty from as early as 6 weeks post diagnosis. It is known that physical activity and exercise is safe and effective for children though it is most commonly conducted as a reactive therapy when children have already significantly deteriorated. Very little is known regarding the pathophysiology that drives sarcopenia in children with cancer, there is optional consent for participants to have their blood samples biobanked for future studies. There are no standardised diagnostic criteria, assessment tools or treatments for sarcopenia or frailty. Often studies limit diagnosis to imaging modalities alone, omitting functional assessment. We will use a standardised criteria incorporating muscle mass and functional measurements (such as hand grip strength). This study aims to explore factor that contribute the frailty including sarcopenia assessment ("muscle strength" and muscle mass "loss of muscle") as well as "slowness", "poor endurance", "low physical activity" The intervention aims to reduce the risk of frailty for participants with early signs of sarcopenia and currently there are no interventions that target frailty directly in children with cancer nor has frailty been investigated in the acute treatment phases of treatment.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sarah Grimshaw, PhD Physiotherapy; Phone Number: +61417162166; Email: sarah.grimshaw@mcri.edu.au
• Study Contact Backup: Name: Ella Thorburn, Bachelor of Physiotherapy(hon); Phone Number: +61415066889; Email: ella.thorburn@student.unimelb.edu.au

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3052
      • Recruiting
      • Royal Children's Hospital
      • Contact: Sarah Grimshaw, PhD Physiotherapy; Phone Number: +61417162166; Email: sarah.grimshaw@mcri.edu.au
      • Contact: Ella Thorburn, Bachelor of Physiotherapy(hon); Phone Number: +61415066889; Email: ella.thorburn@student.unimelb.edu.au
      • Principal Investigator: Sarah Grimshaw, PhD Physiotherapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 5-17 years at the time of consent
• New diagnosis of acute lymphoblastic leukaemia <7 days
• Is planned to receive management for their cancer treatment at the trial site for the duration of the trial period
• Has a legally acceptable representative capable of understanding the informed consent document in English and providing consent on the participant's behalf
• Have a family electronic device that can be linked with the tool to be used (Fitbit)

Exclusion Criteria:

• none

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observation cohort; These participants did not have early signs of sarcopenia at the post induction therapy assessment point, but will be followed up at all timepoints to better understand the natural progression of acute lymphoblastic leukaemia. Usual care is a ward based physiotherapist service which is reactive and referral based only.
No Intervention: Usual care control group; These participants demonstrated early signs of sarcopenia at the post induction phase of treatment assessment point and were randomised to the control group. Usual care is a ward based physiotherapist service which is reactive and referral based only.
Experimental: Intervention group; These participants demonstrated early signs of sarcopenia at the post induction phase of treatment assessment point and were randomised to the intervention group. The intervention group receives 9 weeks of goal setting and physical activity behaviour change coaching, as well as concurrently receiving 8 weeks of structured exercise sessions weekly (45-60 minutes per session x 3/week). These sessions are individualised based on the participant's functional performance outcomes from the assessment prior to randomisation, with a resistance strength training and progressive overload principles. The delivery of the specific exercises will be based on a pragmatic, participation based focus and will incorporate the individual's development stage, age, interests and enjoyment.	Behavioral: Exercise; These participants demonstrated early signs of sarcopenia at the post induction phase of treatment assessment point and were randomised to the intervention group. The intervention group receives 9 weeks of goal setting and physical activity behaviour change coaching (with activity tracking via Fitbit for continuous feedback) as well as concurrent 8 weeks of 3x45-60 minute structured exercise sessions weekly. These are individualised based on their functional performance outcomes from the assessment prior to randomisation with a resistance strength training and progressive overload principles. The delivery of the specific exercises will be based on a pragmatic, participation based focus and will incorporate the individuals development stage, age, interests and enjoyment.; Other Names: physical activity; wearable device; behaviour change

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Qualitative acceptability	Measured by a semi-structured interview designed with Theoretical Domains Framework (TDF) and TFA theory	16 weeks
Mean change in muscle mass of rectus femoris on muscle ultrasound	Muscle mass is measured via ultrasound by cross-sectional area and thickness of rectus femoris at enrolment/diagnosis compared with pre-delayed intensification (post-intervention). This will be used to determine the sample size required for a future randomised controlled trial.	Baseline, 16 weeks
Mean change in grip strength with handheld dynamometry	Grip strength is measured by handheld dynamometry at post-induction (pre-intervention) compared with pre-delayed intensification (post-intervention). This will be used to determine the sample size required for a future randomised controlled trial.	5 weeks, 16 weeks
Mean change in knee extension strength on handheld dynamometry	Knee extension strength is measured by using handheld dynamometry at post-induction (pre-intervention) and pre-delayed intensification (post-intervention). This will be used to determine the sample size required for a future randomised controlled trial.	5 weeks, 16 weeks
Mean change in lean muscle mass on Dual-Energy X-ray Absorptiometry (DEXA) scan	Quantity of lean muscle mass as measured on DEXA scan. This will be used to determine the sample size required for a future randomised controlled trial.	5 weeks and 24 weeks
Fidelity of the intervention	Measured using the National Institutes of Health Behavior Change Consortium (NIH BCC) framework for fidelity of delivery, receipt and enactment.	Post-randomisation through to the final intervention session [anticipated at 15 weeks]
Feasibility of the trial measured by recruitment rate	Number of participants recruited compared with those given the study brief, and reasons for refusal.	through study recruitment completion, approximately 15 months
Feasibility of the trial measured by lost recruitment opportunities	the number of participants screened by the research team compared to number of eligible children admitted to ward across the study period.	through study recruitment completion, approximately 15 months
Feasibility of the intervention measured by the attrition rate	Rate and reasons for attrition of participants from the trial	through study completion, approximately 17 months
Trial safety is measured by the frequency and severity of recorded adverse events related to the trial	Adverse events will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0	through study completion, approximately 17 months
Feasibility of assessments is measured by the number of completed assessments	Percentage of data recorded for each individual outcome measure compared to the number of planned outcome measures, and reasons for non-completed data.	Through study completion, approximately 17 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptability measured by Theoretical Framework of Acceptability (TFA) survey	The TFA is a generic survey specifically altered for the PROTECT study with 9 questions scoring 1-5. A score of 36 or higher is considered acceptable.	Baseline, mid intervention (4-7 weeks), 16 weeks (post intervention)
Satisfaction of participants during the intervention	Using a Smiley face likert scale (5-point scale) of enjoyment, the children will be asked to rate their satisfaction following the completion of the intervention. A score of 4 or more is considered 'enjoyed'.	Post-randomisation through to the final intervention session [anticipated at 15 weeks]
Mean change in lower limb endurance as measured by the 30 second chair stand	Lower limb endurance is measured by the number of stands (established as full hip and knee extension) achieved in 30 seconds. The assessment will be completed in line with the standardised procedures. Change will be measured over time.	5 weeks, 16 weeks and 24 weeks
Mean change in upper limb endurance as measured by the 30 second timed push ups	Upper limb endurance is measured by the number of knee push ups a participant can complete in 30 seconds. This assessment will be carried out in-line with the standardised sub-section of the Bruininks-Oseretsky Test of Motor Proficiency, 2nd Edition (BOT-2).	5 weeks, 16 weeks and 24 weeks
mean change in mobility as assessed by the 10 meter walk run test	Mobility is assessed using the 10-meter walk/run test (10MWRT). This is a timed test that measures walking or running speed over a 10m distance. It's used to assess mobility, gait, and balance. The assessment will be completed in line with the standardised procedures.	5 weeks, 16 weeks and 24 weeks
Mean change in subjective fatigue evaluated by the PROMIS-Fatigue module questionnaire	PROMIS is a set of person-centred measures that evaluates and monitors physical, mental, and social health in children. The PROMIS measures across several health domains. Each domain takes ~ 3 min to complete. Within PROTECT we will use the parent proxy (age 5-17) and Pediatric (age 8-17	5 weeks, 16 weeks, 24 weeks
Mean change in subjective pain experience evaluated by the PROMIS-pain interference and behaviour module questionnaire	PROMIS is a set of person-centred measures that evaluates and monitors physical, mental, and social health in children. The PROMIS measures across several health domains. Each domain takes ~ 3 min to complete. Within PROTECT we will use the parent proxy (age 5-17) and Pediatric (age 8-17	5 weeks, 16 weeks and 24 weeks
Mean change in subjective sleep impairment evaluated by the PROMIS-sleep disturbance and impairment module questionnaire	PROMIS is a set of person-centred measures that evaluates and monitors physical, mental, and social health in children. The PROMIS measures across several health domains. Each domain takes ~ 3 min to complete. Within PROTECT we will use the parent proxy (age 5-17) and Pediatric (age 8-17	5 weeks, 16 weeks and 24 weeks
Mean change in subjective strength evaluated by the PROMIS-Strength impact questionnaire	PROMIS is a set of person-centred measures that evaluates and monitors physical, mental, and social health in children. The PROMIS measures across several health domains. Each domain takes ~ 3 min to complete. Within PROTECT we will use the parent proxy (age 5-17) and Pediatric (age 8-17	5 weeks, 16 weeks, 24 weeks
Mean change in subjective stress evaluated by the PROMIS-psychological stress questionnaire	PROMIS is a set of person-centred measures that evaluates and monitors physical, mental, and social health in children. The PROMIS measures across several health domains. Each domain takes ~ 3 min to complete. Within PROTECT we will use the parent proxy (age 5-17) and Pediatric (age 8-17	5 weeks, 16 weeks and 24 weeks
Mean change in Lumbar spine bone mineral density measured by DEXA	Change over time to Lumbar spine bone mineral density on DEXA scan	5 weeks and 24 weeks
Mean change of appendicular lean muscle mass on DEXA	Change over time to appendicular lean mass measured by DEXA.	5 weeks and 24 weeks
Mean change in hip bone mineral density measured by DEXA	Change over time to hip bone mineral density measured by DEXA.	5 weeks and 24 weeks
Mean change in grip strength with handheld dynamometry	Grip strength assessed with handheld dynamometry at post-induction (pre-intervention), compared to pre-delayed intensification (post-intervention), and post-delayed intensification	5 weeks, 16 weeks and 24 weeks
Mean change in knee extension strength with handheld dynamometry	Knee extension strength assessed with handheld dynamometry at post-induction (pre-intervention), compared to pre-delayed intensification (post-intervention), and post-delayed intensification	5 weeks, 16 weeks and 24 weeks
Mean change in tibialis anterior strength with handheld dynamometry	Tibialis anterior strength assessed with handheld dynamometry at post-induction (pre-intervention), compared to pre-delayed intensification (post-intervention), and post-delayed intensification	5 weeks, 16 weeks and 24 weeks
Mean change in rectus femoris muscle measured on muscle ultrasound	Muscle changes measured on ultrasound via the cross-sectional area, thickness and echogenicity of rectus femoris at enrolment/diagnosis compared with post-induction (pre-intervention) and pre delayed intensification (post-intervention), and post-delayed intensification.	Baseline, 5 weeks, 16 weeks, 24 weeks
Mean change in tibialis anterior muscle measured on muscle ultrasound	Muscle changes measured on ultrasound via the cross-sectional area, thickness and echogenicity of tibialis anterior at enrolment/diagnosis compared with post-induction (pre-intervention) and pre delayed intensification (post-intervention), and post-delayed intensification.	Baseline, 5 weeks, 16 weeks, 24 weeks
Mean change in vastus lateralis muscle measured on muscle ultrasound	Muscle changes measured on ultrasound via the cross-sectional area, thickness and echogenicity of vastus lateralis at enrolment/diagnosis compared with ultrasound at enrolment/diagnosis compared with post-induction (pre-intervention) and pre delayed intensification (post-intervention), and post-delayed intensification.	Baseline, 5 weeks, 16 weeks, 24 weeks
Mean change in steps per day	Measured using the Fitbit Inspire 3 for a 7 day period at post-induction (pre-intervention), compared to pre-delayed intensification (post-intervention), and post-delayed intensification.	5 weeks, 16 weeks, 24 weeks
Mean change in sedentary time per day	Measured using the Fitbit Inspire 3 for a 7 day period at post-induction (pre-intervention), compared to pre-delayed intensification (post-intervention), and post-delayed intensification.	5 weeks, 16 weeks, 24 weeks
Mean change in malnutrition measured by Malnutrition Score	The Malnutrition Score identifies the presence and severity of malnutrition based on changes in age-related z scores for BMI.	5 weeks, 16 weeks and 24 weeks
Mean change in lower limb power evaluated by Jump Forward	Long jump measures the furthest horizontal distance (cm) jumped from a standing start. The assessment will be completed in line with standardised procedures.	5 weeks, 16 weeks and 24 weeks
Mean change in mobility endurance evaluated by the 100-meter Timed Test (100mTT)	Mobility endurance is assessed using the 100mTT. This is a timed test that measures walking or running speed over a 100m distance. It's used to assess mobility, gait, and balance. The assessment will be completed in line with the standardised procedures.	5 weeks, 16 weeks, 24 weeks
Mean change for ability to climb stairs as measured by the Timed Up and Down Stairs (TUDS)	Ability to climb stairs will be measured using the TUDS conducted on a set of 13 stairs with handrails. The time taken to walk up the stairs, turn around, and walk back down as quickly as possible was recorded. The assessment will be completed in line with the standardised procedures.	5 weeks, 16 weeks and 24 weeks
Mean change in ability to rise from the floor as measured by the Time Rise from Floor - quality assessment (TRF)	Ability to rise from floor is measured by the TRF which starts in supine and the participant rises from the floor. A graded quality assessment is conducted. The test will be conducted in line with standardised procedures.	5 weeks, 16 weeks and 24 weeks
Mean change in ability to rise from the floor and walk 6m and sit back down evaluated by the Timed Floor To Stand - Natural (TFTS-N)	TFTS-N is a timed test conducted from sitting to standing, walking around a cone placed 3m away, and returning to sitting. The test will be conducted in line with standardised procedures.	5 weeks, 16 weeks, 24 weeks
Mean change in endurance as evaluated by the 6-Minute Walk Test (6MWT)	Measured by the total distance (m) walked in 6 minutes. The assessment will be completed in line with standardised procedures. Assessed at post-induction (pre-intervention), compared to pre-delayed intensification (post-intervention), and post-delayed intensification	5 weeks, 16 weeks and 24 weeks
Mean change in chemotherapy-induced peripheral neuropathy as measured by the Paediatric modified Total Neuropathy Score (Ped m-TNS)	Chemotherapy-induced peripheral neuropathy will be assessed using the Ped m-TNS. This is a standardised assessment that combines subjective and objective components, yielding a score indicating the severity of neuropathy. Assessment will be carried out in accordance with standard procedures. Assessed at post-induction (pre-intervention), compared to pre-delayed intensification (post-intervention), and post-delayed intensification.	5 weeks, 16 weeks and 24 weeks
Mean change in subjective physical activity evaluated by the Patient-Reported Outcomes Measurement Information System (PROMIS)-Physical Activity questionnaire	PROMIS is a set of person-centred measures that evaluates and monitors physical, mental, and social health in children. The PROMIS measures several health domains. Each domain takes ~ 3 min to complete. Within PROTECT, we will use the parent proxy (age 5-17) and the Paediatric (age 8-17) questionnaires. Assessed at post-induction (pre-intervention), compared to pre-delayed intensification (post-intervention), and post-delayed intensification.	5 weeks, 16 weeks and 24 weeks
Mean change in subjective sarcopenia measured via the Ped-SARC-F (Paediatric, Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls): subjective sarcopenia questionnaire	The PED-SARC-F is a screening tool used to identify sarcopenia in pediatric patients, particularly those undergoing haemato-oncology treatment. The PED-SARC-F is a child-specific version of the standard SARC-F questionnaire used to assess sarcopenia in adults.	5 weeks, 16 weeks and 24 weeks
Mean change in subjective upper limb function evaluated by the PROMIS-Upper Limb Function questionnaire	PROMIS is a set of person-centred measures that evaluates and monitors physical, mental, and social health in children. The PROMIS measures several health domains. Each domain takes ~ 3 min to complete. Within PROTECT, we will use the parent proxy (age 5-17) and the Paediatric (age 8-17) questionnaires. Assessed at post-induction (pre-intervention), compared to pre-delayed intensification (post-intervention), and post-delayed intensification.	5 weeks, 16 weeks and 24 weeks

Collaborators and Investigators

• Sponsor: Murdoch Childrens Research Institute
• Investigators: Study Director: Rachel Conyers, A/Prof Paediatric Oncologist, Murdoch Children's Research Institute, Royal Children's Hospital (Melbourne), University of Melbourne

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2026
• Primary Completion (Estimated): July 17, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: December 18, 2025
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Actual): January 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: physical activity; exercise; behaviour change; paediatrics
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Manifestations; Neoplasms; Pathological Conditions, Anatomical; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Muscular Atrophy; Atrophy; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sarcopenia; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Equipment and Supplies; Electrical Equipment and Supplies; Exercise; Wearable Electronic Devices
• Other Study ID Numbers: 2025/ETH01569

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is an optional consent for the data collected to be used in future studies however, there are no data sharing agreements in place and therefore future studies would be using data under the original data agreements and protocols. A protocol publication is planned and will be linked to the registration when it is complete.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No