Evaluation of PeRsOnalised PrEhabilitation in acute myeloid Leukaemia (PROPEL)

BACKGROUND

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. AIM AND OBJECTIVES

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).

Primary Objective: To compare fatigue measured by the Functional Assessment of Chronic Illness Therapy fatigue (FACIT-F) scale.

Secondary Objectives: To assess QoL and emotional wellbeing, survival, and cost-effectiveness and to conduct a process evaluation. METHODS

Design: Multicentre, open-label randomised controlled trial comparing BPUC with PPCP incorporating a 12-month internal pilot, parallel process evaluation and economic evaluation. Setting: UK hospitals caring for people with AML. Population: Diagnosis of AML or MDS-EB2, in complete remission following induction chemotherapy.

Interventions:

BPUC: Online or printed prehabilitation information on emotional wellbeing, nutrition and physical activity, given once, prior to second chemotherapy course.

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. Primary outcome: Fatigue

Secondary outcomes: • Wellbeing, QoL, distress, physical function, weight change, macronutrient intake • Onward referrals for ‘specialist’ services • Completion of treatment courses • Overall and relapse-free survival • Cost-effectiveness • Process Evaluation

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.

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. TIMELINE

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. ANTICIPATED IMPACT AND DISSEMINATION

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.