Personalised prehabilitation in acute myeloid leukaemia

Plain English Summary

Background and study aims
Patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome with excess blasts (MDS-EB2) (types of blood cancer) often present as a medical emergency and require urgent intensive treatment of chemotherapy and in some cases a haematopoietic stem cell transplant (HSCT) for up to 6 months. Patients say that going through this treatment can make them feel very tired (fatigued), have low mood, poor nutrition and be unable to do any exercise. Being able to complete the treatment is very important to improve the chances of survival for people with AML. Programmes that help patients and their carers to prepare for treatment by providing extra information or treatment to improve nutrition, exercise and mood are known as prehabilitation programmes. Currently, prehabilitation prior to chemotherapy or stem cell transplant is not always offered to people with AML or MDS and there is no research in this area. However, research in other cancers for people undergoing surgery has shown that prehabilitation can improve quality of life and survival, reduce tiredness and complications, and help patients complete their treatment. This study aims to see if prehabilitation can help patients with AML or MDS get through all cycles of intensive chemotherapy and HSCT. The researchers are investigating if a prehabilitation prescription that includes remote support for emotional wellbeing, nutrition and exercise can reduce tiredness, improve quality of life, and treatment outcomes for patients with AML or MDS when compared to any prehabilitation that is offered in hospitals now.

Who can participate?
Patients aged 16 years and over with AML or MDS-EB2 in complete remission following induction chemotherapy

What does the study involve?
Participants will be randomly allocated to either:
1. Best practice usual care (control) which is in addition to prehabilitation care received as standard practice at site. It involves a 30-minute virtual prehabilitation discussion with a member of the central team, the participant with or without their caregiver where appropriate, once only and prior to the first cycle of consolidation chemotherapy. It will be based on Maggie’s Prehabilitation Guidance and provides the participant with online or printed generic and freely available prehabilitation information on emotional wellbeing, nutrition, and physical activity.
2. Personalised Prehabilitation Care Plan (PPCP) is in addition to prehabilitation care received as standard practice at site. It involves information plus personalised support for emotional wellbeing, nutrition and physical activity. It will be offered before each consolidation cycle of chemotherapy and HSCT, if given. The PPCP will be developed based on screening and assessment of the person with AML by a central team of prehabilitation experts, with input from local staff and a caregiver (if appropriate). The PPCP will include advice on nutrition, physical activity and managing emotional well-being as required. Additionally, participants will be offered a range of remote support sessions delivered by a central specialist team (psychological wellbeing practitioners with clinical psychologist supervision, clinical exercise physiologist/physiotherapist/ Can-REHAB coaches and dietitians). Local staff will be trained to provide ongoing behavioural support to participants via regular check-ins, to encourage adherence to the intervention. PPCP will mirror each consolidation cycle of chemotherapy and HSCT (if given).

What are the possible benefits and risks of participating?
We do not know whether the remote prehabilitation care package will improve your quality of life or ability to tolerate treatment, but you may feel more supported, whichever group you are in. You may not directly benefit from taking part in this research, but your participation may provide evidence to help guide treatment in this area in the future for patients with AML or MDS.
We do not anticipate there to be any serious risks to you, and we do not expect any patients to come to harm. There is a very small chance exercise can make you feel unwell. Exercise may also cause tiredness, breathlessness and sore muscles, but this should get a bit easier each time you exercise. For your safety, we recommend that you have another person nearby when exercising at home during your first few exercise sessions. During an inpatient stay you may wish to ask a member of staff on your ward to be present or do the session during a visit from a friend or family. Sometimes, people can also find the support sessions upsetting. Our PROPEL specialists are fully trained and will provide appropriate support and assistance if needed.

Where is the study run from?
Warwick Clinical Trials Unit, University of Warwick (UK)

When is the study starting and how long is it expected to run for?
September 2022 to August 2027

Who is funding the study?
National Institute for Health and Care Research (NIHR) Health Technology Assessment Programme (UK)

Who is the main contact?
PROPEL@warwick.ac.uk

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-personalised-prehabilitation-for-myeloid-leukaemia-and-myelodysplastic-syndrome

Study website

https://warwick.ac.uk/fac/sci/med/research/ctu/trials/propel/

Type

Scientific

Contact name

Dr Alice Longe

ORCID ID

Contact details

Warwick Medical School
University of Warwick
Coventry
CV4 7AL
United Kingdom
+44 (0)2476 151 661
Alice.longe@warwick.ac.uk

EudraCT/CTIS number

Nil known

IRAS number

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 56018, IRAS 320489

Scientific title

PROPEL: Evaluation of PeRsOnalised PrEhabilitation in people with acute myeloid Leukaemia

Acronym

PROPEL

Study hypothesis

Personalised prehabilitation care package (PPCP) will improve patients’ experience of fatigue during treatment in comparison to best practice usual care (BPUC), by supporting patients to manage their emotions, be physically active, and eat an appropriate diet.

Ethics approval(s)

Approved 30/05/2023, London – Surrey Borders (Currently being held remotely via Teleconference/ZOOM, London, None available, United Kingdom; +44 (0)207 104 8057; surreyborders.rec@hra.nhs.uk), ref: 3/LO/0347

Study design

Randomized; Interventional; Design type: Treatment, Prevention, Education or Self-Management, Dietary, Psychological & Behavioural, Complex Intervention, Physical, Rehabilitation

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Study setting(s)

Hospital, Internet/virtual

Study type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Acute myeloid leukaemia (AML)

Intervention

PROPEL is a multicentre, randomised controlled trial comparing best practice usual care (BPUC) with a personalised prehabilitation care package (PPCP) incorporating a 12-month internal pilot, parallel process evaluation and economic evaluation. The aim is to establish the clinical impact and cost-effectiveness of best practice usual care (BPUC) compared to a multiphasic, multimodal personalised prehabilitation care package (PPCP) on fatigue, emotional wellbeing, and quality of life (QoL) in patients in remission following induction chemotherapy. PROPEL plans to recruit 600 participants, who will be randomised on a 1:1 basis.

Patients who are confirmed to be eligible will be invited to take part in the study and if, following a review of the patient information sheet, they decide to participate, written informed consent will be obtained.

Participants will be eligible if they are aged 16 years or over, have a diagnosis of AML or MDS-EB2 and are in complete remission following induction chemotherapy or have relapsed AML for which they have achieved a further complete remission with an intent to deliver further intensive consolidation treatment +/- haematopoietic stem cell transplantation (HSCT).

Baseline: Prior to randomisation, participants will be issued with a baseline questionnaire, they will also be asked to complete a number of assessments including food diaries, a 6-minute walk test, a hand grip strength test, calf circumference as well as providing clinical information.

Participants will be randomised on a 1:1 basis using a computer minimisation algorithm based on the following variables:
1. Age (<= 60; >60 years)
2. Baseline fatigue (none, mild, moderate, severe)
3. Performance status (Karnofsky performance status: 100-80; 70-50; 40-0)
4. Intention to proceed to HSCT (yes; no)

Participants either receive:
1. BPUC: BPUC is a 30-minute virtual prehabilitation discussion with a member of the central team, the participant +/- their caregiver where appropriate, once only and prior to the first cycle of consolidation chemotherapy. It will be based on Maggie's prehabilitation guidance and provides the participant with online or printed generic and freely available prehabilitation information on emotional wellbeing, nutrition, and physical activity.
2. PPCP: PPCP is information plus personalised support for emotional wellbeing, nutrition and physical activity. It will be offered before each consolidation cycle of chemotherapy and HSCT, if given. The PPCP will be developed based on screening and assessment of the person with AML by a central team of prehabilitation experts, with input from local staff and a caregiver (if appropriate). The PPCP will include advice on nutrition, physical activity and managing emotional well-being as required. Additionally, participants will be offered a range of remote support sessions delivered by a central specialist team (psychological wellbeing practitioners with clinical psychologist supervision, clinical Exercise physiologist/ physiotherapist/Can-REHAB coaches and dietitians). Local staff will be trained to provide ongoing behavioural support to participants via regular check-ins, to encourage adherence to the intervention.

PPCP will mirror each consolidation cycle of chemotherapy and HSCT and should commence on day 28 +/- 7 days [post nadir, at least 8 days prior to commencing the next consolidation cycle]. The intervention will continue throughout each cycle and HSCT (if given)

Follow-up: To limit the burden on participants, only primary outcome and key secondary outcome data will be collected prior to each cycle of chemotherapy. Primary and secondary outcomes will be assessed in person at 3 months follow-up post-completion of treatment (either chemotherapy or HSCT) and at 24 months post-randomisation. Follow-up data for relapse and death will be collected for a minimum of 24 months after trial entry and up to 5 years.

Process evaluation: A theoretically informed mixed methods process evaluation consisting of a fidelity and intervention dose assessment across all intervention sites, measurement of any behaviour change differences between intervention and control groups across all sites, and a qualitative interview study focused on six sites. Up to 4 participants per arm, as well as local healthcare professionals (HCPs), key managers and intervention specialists will be interviewed.

Aims: To investigate issues that may affect the delivery and outcomes of the intervention and assess the feasibility of implementing the intervention widely in the NHS

Objectives:
1. To investigate intervention delivery fidelity and impact dose of the PROPEL intervention model.
2. To investigate patients’, local site PROPEL Trained HCPs’, managers’, remote delivery practitioners and central research team multidisciplinary hub members’ experiences of the intervention, how and why the intervention did or did not facilitate change among participants, at a sample of six sites, and
3. To explore how the intervention delivery was implemented by the remote delivery practitioners at the sample of six sites and how that implementation affected how the intervention package was delivered and received.

Intervention type

Behavioural

Primary outcome measure

Subjective levels of fatigue measured using Functional Assessment of Chronic Illness Therapy (FACIT-F) fatigue scale at baseline, following each cycle of treatment, 3 months post EOT and 24 months post randomisation

Secondary outcome measures

1. Emotional wellbeing measured using the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) at baseline, following each cycle of treatment, 3 months post EOT and 24 months post randomisation
2. Anxiety and depression measured using the Patient Health Questionnaire 9-item (PHQ-9) and General Anxiety Disorder 7-item (GAD7) at baseline, following each cycle of treatment, 3 months post EOT and 24 months post randomisation
3. Health-related quality of life measured using FACIT-F and EQ-5D-5L at baseline, following each cycle of treatment, 3 months post EOT and 24 months post randomisation
4. Physical function measured using Karnofsky Performance Scale at baseline, following each cycle of treatment, 3 months post EOT and 24 months post randomisation
5. Physical function measured using 6-min walk test at baseline, 3 months post EOT and 24 months post randomisation
6. Physical function measured using hand grip strength test at baseline, EOT, 3 months post EOT and 24 months post randomisation
7. Presence or absence of sarcopenia measured using SARC-F and calf circumference at baseline, EOT, 3 months post EOT and 24 months post randomisation
8. Incidence of malnutrition and its determinants measured using MUST, percentage weight change; BMI at baseline, following each cycle of treatment, 3 months post EOT and 24 months post randomisation
9. Incidence of malnutrition and its determinants measured using dietary intake from a 3-day food diary at baseline, following each cycle of treatment and 3 months post EOT
10. Completion of treatment cycles assessed using the number of cycles of chemotherapy completed +/- HSCT following each cycle of treatment
11. Onward referrals for ‘specialist’ services measured using the number of onward referrals to local services for ‘specialist’ therapies following each cycle of treatment
12. Overall and relapse-free survival assessed using clinical records at up to 5 years post randomisation
13. Readmissions to hospital, ICU admission, number of transfusions, complications of HSCT, adverse events and serious adverse events assessed using clinical hospital records following each cycle of treatment
14. Cost, cost-effectiveness and cost-utility measured using resource use costs, cost and EQ-5D-5L following each cycle of treatment, 3 months post EOT and 24 months post randomisation
15. Process evaluation: fidelity to intervention delivery and dose of intervention received for each component assessed using research records collected throughout the intervention, assessed at the end of intervention delivery
16. Process evaluation: evaluation through qualitative interviews at six sites. 2 sites will be identified during the pilot phase (12 months), with the remaining four identified during the main trial
17. Mechanisms of action: psychological flexibility and motivation measured using CompACT questionnaires and adapted COMB-Q at baseline, following each cycle of treatment, 3 months post EOT and 24 months post randomisation

Overall study start date

01/09/2022

Overall study end date

31/08/2027

Reason abandoned (if study stopped)

Participant inclusion criteria

1. Age ≥16 years, treated on adult AML pathway
And either:
2. Diagnosis of either AML or MDS-EB2 (MDS with 10% blasts in the bone marrow)
3. In complete remission at the completion of induction chemotherapy (defined <5% blasts)
4. Intention to undertake consolidation treatment (chemotherapy +/- HSCT)
*Patients undergoing venetoclax-based treatment are only eligible if an HSCT is planned
OR
5. Relapsed AML who have achieved a further complete remission, with an intent to deliver further intensive consolidation treatment +/- HSCT
6. Access to the internet and an email address
7. Willing to use videoconferencing to undertake the appointments and sessions

Participant type(s)

Patient

Age group

Adult

Lower age limit

16 Years

Sex

Both

Target number of participants

Planned Sample Size: 600; UK Sample Size: 600

Participant exclusion criteria

1. Diagnosis of acute promyelocytic leukaemia
2. Undergoing non-intensive treatment (e.g. single-agent azacitidine, low-dose cytarabine)

Recruitment start date

01/06/2023

Recruitment end date

31/08/2025

Countries of recruitment

England, United Kingdom, Wales

Study participating centre

Doncaster Royal Infirmary
Armthorpe Road
Doncaster
DN2 5LT
United Kingdom

Study participating centre

Queen Elizabeth Hospital
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom

Study participating centre

St James University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom

Study participating centre

Rotherham General Hospital
Moorgate Road
Rotherham
S60 2UD
United Kingdom

Study participating centre

Manchester Royal Royal Infirmary
Cobbett House
Oxford Road
Manchester
M13 9WL
United Kingdom

Study participating centre

University Hospitals Coventry & Warwickshire
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Study participating centre

Bristol Haematology & Oncology Centre
Horfield Road
Bristol
BS2 8ED
United Kingdom

Study participating centre

Royal Sussex County Hospital
Eastern Road
Brighton
BN2 5BE
United Kingdom

Study participating centre

Basingstoke and North Hampshire Hospital
Aldermaston Road
Basingstoke
RG24 9NA
United Kingdom

Study participating centre

Northwick Park & St Marks Hospital
Watford Road
Harrow
HA1 3UJ
United Kingdom

Study participating centre

Clatterbridge Cancer Centre - Liverpool
65 Pembroke PLACE
Liverpool
L7 8YA
United Kingdom

Study participating centre

City Hospital
Dudley Road
Birmingham
B18 7QH
United Kingdom

Study participating centre

Hinchingbrooke Hospital
Hinchingbrooke Park
Huntingdon
PE29 6NT
United Kingdom

Study participating centre

St Georges Hospital
Blackshaw Road
Tooting
London
SW17 0QT
United Kingdom

Study participating centre

Hammersmith Hospital
Du Cane Road
Hammersmith
London
W12 0HS
United Kingdom

Study participating centre

Glan Clwd Hospital
Ysbyty Glan Clwydd
Bodelwyddan
Rhyl
LL18 5UJ
United Kingdom

Study participating centre

Uclh
250 Euston Road
London
NW1 2PQ
United Kingdom

Study participating centre

Freeman Road Hospital
Freeman Road
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Study participating centre

Great Western Hospital
Marlborough Road
Swindon
SN3 6BB
United Kingdom

Study participating centre

Nottingham City Hospital
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Study participating centre

Wirral University Teaching Hospital
Arrowe Park Road
Wirral
CH49 5PE
United Kingdom

Study participating centre

Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom

Study participating centre

Doncaster Royal Infirmary
Armthorpe Road
Doncaster
DN2 5LT
United Kingdom

Study participating centre

Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom

Study participating centre

Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
United Kingdom

Study participating centre

University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom

Study participating centre

Stoke Mandeville Hospital
Mandeville Road
Aylesbury
HP21 8AL
United Kingdom

Study participating centre

Salisbury District Hospital
Salisbury District Hospital
Odstock Road
Salisbury
SP2 8BJ
United Kingdom

Study participating centre

Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Study participating centre

Aberdeen Royal Infirmary
Foresterhill Road
Aberdeen
AB25 2ZN
United Kingdom

Study participating centre

Victoria Hospital (blackpool)
Whinney Heys Road
Blackpool
FY3 8NR
United Kingdom

Study participating centre

The Royal Marsden Hospital
Fulham Road
London
SW3 6JJ
United Kingdom

Study participating centre

Addenbrookes
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Study participating centre

James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Study participating centre

Royal Cornwall Hospital (treliske)
Treliske
Truro
TR1 3LJ
United Kingdom

Study participating centre

Raigmore Hospital
Old Perth Rd
Inverness
IV2 3UJ
United Kingdom

Study participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Study participating centre

Pinderfields Hospital
Aberford Road
Wakefield
WF1 4DG
United Kingdom

Study participating centre

Kings College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom

Study participating centre

Royal Devon and Exeter Hospital
Royal Devon & Exeter Hospital
Barrack Road
Exeter
EX2 5DW
United Kingdom

Study participating centre

Christie Hospital
550 Wilmslow Road
Withinton
Manchester
M20 4BX
United Kingdom

Organisation

University of Warwick

Sponsor details

University House
Gibbet Hill Road
Coventry
CV4 7AL
England
United Kingdom
+44 (0)24 765 75733
sponsorship@warwick.ac.uk

Sponsor type

University/education

Website

http://www2.warwick.ac.uk/

ROR

https://ror.org/01a77tt86

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR134257

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

The definitive research findings will be reported via a published HTA monograph (NIHR Library), alongside publications in open-access, high-impact, peer-review journals (trial protocol, primary clinical results, economic evaluation, process evaluation). These will be linked with presentations at relevant conferences, nationally and internationally (haematology and other societies), to which PPI members will be invited within 1 year after the overall study end date.

Intention to publish date

31/08/2028

Individual participant data (IPD) sharing plan

The datasets generated during the current study will be available upon request through the CI (PROPEL@warwick.ac.uk) after trial publication. A proposal describing the purpose, scope, data items requested, analysis plan and including appropriate acknowledgment of the PROPEL trial management group) should be provided for approval from the PROPEL TMG. Any data transfer would be in accordance with the University of Warwick SOPs and require data sharing/processing agreements to be in place. Participant Consent for future research is requested.

IPD sharing plan summary

Available on request

Study outputs