Title: Evaluation of PeRsOnalised PrEhabilitation in acute myeloid Leukaemia (PROPEL)
Funder: Department of Health and Social Care

Abstract: Background: Acute myeloid leukaemia (AML), the most common acute leukaemia, is an ‘aggressive’ blood cancer with around 20% of affected adults surviving at 5 years. AML often presents as a medical emergency. Treatment starts within days. After the initial course of urgent anticancer therapy, people with AML receive repeated intensive courses of chemotherapy aimed at cure, that may include ‘haemopoietic’ (blood) stem cell transplantation. They need to remain in hospital during courses of treatment, often in isolation, due to risk of infection, with short periods at home to recover. This treatment results in huge effects on physical, nutritional and mental health. Caregivers are also deeply affected by the care pathway. Cancer-related fatigue is the most debilitating problem for people with AML, and often continues long into recovery, affecting life beyond cancer for survivors._x000D_ _x000D_ The research: ‘Prehabilitation’ aims to improve physical and psychological wellbeing after diagnosis, to help people with AML get through the intensive treatment courses including to stem cell transplant which is often critical for cure. Our research will test whether a package of enhanced personalised prehabilitation can help people with AML cope better with treatment, with less fatigue, compared to prehabilitation care that happens now (best practice usual care). _x000D_ _x000D_ We have designed a clinical trial, ‘PROPEL’, involving 600 people treated for AML, who will be allocated at random by computer into either:_x000D_ _x000D_ 1. Best practice usual care, i.e. online or printed prehabilitation information on caring for psychological health, nutrition and physical activity and a 30 minute conversation with a health professional, given once, before the second chemotherapy course; or _x000D_ 2. A ‘prehabilitation’ care package comprising information plus a personalised care plan of tailored support for psychological wellbeing, nutrition and physical activity offered before chemotherapy courses 2 and 3 where given, including transplant. The personalised care plan will be developed by the person with AML and their nominated carer (if present) with input from the central expert team (psychologist, dietitian, physical activity and behaviour specialists) and according to the person’s need, via remote consultation._x000D_ _x000D_ Delivery: The trial will be conducted through hospital nurses and allied healthcare professionals (local team). Different local staff will be trained to deliver usual care or the personalised care plan, supported by the core central expert team._x000D_ _x000D_ Measurements: A questionnaire booklet (completed on paper or online) will be used to capture information on fatigue, wellbeing, mood and distress plus a food diary before each chemotherapy and three months after treatment completion; weight and other physical measurements will also be collected. Costs of the trial options will be estimated to explore value for money for the National Health Service (NHS)._x000D_ _x000D_ We will also interview people with AML and healthcare professionals, to explore views on PROPEL and on taking prehabilitation into the NHS._x000D_ _x000D_ Team: Our team includes people with AML, caregivers, haematologists and experts in research, clinical psychology, behaviour, nutrition and physical activity._x000D_ _x000D_ PROPEL has potential to change prehabilitation for people with AML nationally and globally, improving treatment experience and future wellbeing whilst being value for money.

Lay abstract: BACKGROUND_x000D_ Acute myeloid leukaemia (AML) is the most common acute leukaemia; 5-year survival in adults is around 20%. Treatment aimed at cure requires multiple courses of intensive chemotherapy that may include haemopoietic stem cell transplant (HSCT). Fatigue from disease and treatment is hugely debilitating for people with AML and is linked with poor appetite, muscle loss and low psychological wellbeing. Prehabilitation may improve fatigue and result in physical and psychological resilience, enabling completion of treatment courses, yet is not formally offered in the NHS. Uncertainty remains on the impact of prehabilitation for people with AML._x000D_ _x000D_ AIM AND OBJECTIVES_x000D_ Aim: 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 receiving remission consolidation treatment for AML or high-risk myelodysplastic syndromes with excess blasts (MDS-EB2)._x000D_ _x000D_ Primary Objective: To compare fatigue measured by the Functional Assessment of Chronic Illness Therapy fatigue (FACIT-F) scale._x000D_ _x000D_ Secondary Objectives: To assess QoL and emotional wellbeing, survival, and cost-effectiveness and to conduct a process evaluation. _x000D_ _x000D_ METHODS_x000D_ Design: Multicentre, open-label randomised controlled trial comparing BPUC with PPCP incorporating a 12-month internal pilot, parallel process evaluation and economic evaluation._x000D_ _x000D_ Setting: UK hospitals caring for people with AML. _x000D_ _x000D_ Population: Diagnosis of AML or MDS-EB2, in complete remission following induction chemotherapy._x000D_ _x000D_ Interventions: _x000D_ BPUC: Online or printed prehabilitation information on emotional wellbeing, nutrition and physical activity, given once, prior to second chemotherapy course._x000D_ PPCP: Information plus tailored support for emotional wellbeing, nutrition and physical activity offered before each chemotherapy course and HSCT, if given. PPCP is developed by the person with AML and caregiver with advice from a central team of experts, delivered by trained local staff._x000D_ _x000D_ Primary outcome: Fatigue_x000D_ Secondary outcomes:_x000D_ • Wellbeing, QoL, distress, physical function, weight change, macronutrient intake _x000D_ • Onward referrals for ‘specialist’ services_x000D_ • Completion of treatment courses_x000D_ • Overall and relapse-free survival_x000D_ • Cost-effectiveness_x000D_ • Process Evaluation_x000D_ _x000D_ Sample size: 300 patients in each arm will allow the detection of a standardised difference of 0.3 (e.g. 4 point difference with standard deviation of 13) in the FACIT-F fatigue subscale scores with 90% power, 5% two-sided significance, allowing for 20% dropout._x000D_ _x000D_ Primary analysis: A longitudinal mixed effects regression model will be used to estimate the effect of BPUC compared to PPCP on fatigue, adjusted for patient factors including age, performance status, treatment received._x000D_ _x000D_ TIMELINE _x000D_ 60-month grant: 6 months set up, recruitment over 30 months from 50 sites at an average of 20-30 patients per month, 24 months for intervention delivery, follow-up, process evaluation, analyses, write up and dissemination._x000D_ _x000D_ ANTICIPATED IMPACT AND DISSEMINATION _x000D_ PROPEL has the potential to change practice nationally and globally. Results will be presented at scientific meetings and published in leading journals. Working with patient partners, charities and guideline writers will ensure timely dissemination using appropriate media.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS