Investigating COVID-19 infection in patients with acute myeloid leukaemia (AML) undergoing chemotherapy

Plain English summary of protocol

Background and study aims
The pandemic of Coronavirus disease 2019 (COVID-19) is having major implications on healthcare globally with an estimated around 1-2% of patients dying from the disease. This risk increases with age and this is particularly important for patients with cancer where age is also a risk factor. It is possible a large proportion of the population could become infected with COVID-19. As the prevalence of COVID-19 in the UK is not known due to limited testing, it is not possible to accurately estimate what proportion of patients will have a history of, or will go on to develop, COVID-19. In patients over the age of 60, the hospitalisation rate is estimated to be around 16%, with a quarter requiring Intensive care support and a death rate of 2%.

Acute Myeloid Leukaemia (AML) is a type of cancer that starts in the bone marrow, where the blood cells that fight infections in the body are produced. AML affects predominantly the elderly with a peak of cases at over 70 years of age. There is some early evidence to suggest that patients with cancer are more likely to develop severe COVID-19 disease. Patients during the pandemic will continue to develop AML and it is not possible to delay starting treatment for this aggressive disease for the number of months it may take for the current pandemic to subside. AML is potentially curable with intensive chemotherapy and therefore the recommendation has been not to delay starting treatment. However, there is no data to inform practice in patients with AML who develop COVID-19. A recommendation is to test all patients with a new diagnosis of AML for COVID-19. At present, it is not clear whether patients should be managed with intensive, inpatient standard chemotherapy schedules that will leave patients more immunosuppressed but with better cancer survival rates. This will also require a longer bed occupancy which is a critical issue during this coronavirus pandemic. Furthermore, early evidence suggests that SARS-CoV2 transmission between cancer patients is largely dependent on hospital-acquired transmission. Therefore, it will be important to understand the survival of patients treated with both intensive and non-intensive chemotherapy schedules during this era.

A further complication is that patients with AML are well established to be vulnerable to severe invasive bacterial and fungal infections; infection remains a major cause of morbidity and mortality in AML. It is important to rapidly define the impact of COVID-19 infection on the mortality rate and how best to manage COVID-19 alongside these expected bacteria/fungal invasive infections.

This study aims to collect data on the outcomes of patients with AML who develop COVID-19 infection, and the rates and severity of all infections in patients with AML undergoing intensive chemotherapy, including in those who have recovered from prior COVID-19 infection or who develop COVID-19. This information will be essential to design new studies and update current recommendations.

Who can participate?
Adult patients with acute myeloid leukaemia (AML) or Myelodysplastic Syndrome With Excess Blasts (MDS-EB2) currently receiving, or due to receive, treatment.

What does the study involve?
Demographic data and medical history will be collected for all participants at the start of the study. This will include pre-existing conditions such as diabetes and any history of COVID-19 infection. All patients will also be tested at baseline for COVID-19 and this data will be collected. Data will also be collected on the patient's treatment plan for their AML.

For the 6 months after joining the study, data will be collected on each participant on a weekly basis. Information can be obtained from the hospital notes so patients do not need to attend the clinic. This will include data on any COVID-19 diagnosis, symptoms and outcome, and data on any hospital admissions. Type of infection, diagnostic assessments, antibiotic/antifungal prophylaxis, and how these are treated will be reported. At monthly intervals, there will be an additional form to provide data on any bone marrow assessments the patient has had for their AML and also their survival status. Patients will be followed up for survival until the end of the study. Then, for the following 6 months, patients will be followed up 3 monthly for evidence of COVID-19 infection, AML treatment, and disease response and survival.

If the patient has consented to participate in the sampling sub-study, blood, stool, saliva, and sputum samples would be requested upon entry into the sub-study, and every month for 6 months. Additional samples are requested if the patient is hospitalised with an infection (upon admission to hospital, and 4 weeks later). If a patient doesn't wish to provide a certain sample, or if it is inappropriate to ask for a sample at a certain timepoint, the time point should be missed.

What are the possible benefits and risks of participating?
Participants will be fully informed of the risks and benefits of taking part in the study, along with the burdens involved. As the main study is a non-interventional study that will only collect data and there are no assessments additional to standard of care, the risks are minimal. Any additional risks and burdens through participating in the optional sampling sub-study have been described in the PIS. It is hoped the information gained from this study may help to improve the care of AML patients in the future. The sample collection in the sub-study will not result in any additional visits for patients and blood samples would be taken at the same time as any routine samples.

Where is the study run from?
University of Birmingham (UK)

When is the study starting and how long is it expected to run for?
From January 2020 to March 2023

Who is funding the study?
Cure Leukaemia (UK) and the National Institute for Health Research (UK)

Who is the main contact?
pace@trials.bham.ac.uk

Contact information

Prof Simon Standworth
Principal Investigator

University of Oxford
John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

ORCID ID	0000-0002-7414-4950
Phone	+44 (0)1865 741166
Email	simon.stanworth@nhsbt.nhs.uk

Ms Tina Tang
Public

Cancer Research UK Clinical Trials Unit (CRCTU)
Centre of Clinical Haematology
University of Birmingham
Edgbaston
Birmingham
B15 2TH
United Kingdom

Phone	+44 (0)121 371 7863
Email	pace@trials.bham.ac.uk

Study information

Eligibility

Locations

Countries of recruitment

• England
• Northern Ireland
• Scotland
• United Kingdom
• Wales

Study participating centres

Sponsor information

University of Birmingham
Hospital/treatment centre

Research Support Group
Birmingham
B15 2TT
England
United Kingdom

Phone	+44 (0)121 4158011
Email	researchgovernance@contacts.bham.ac.uk
Website	http://www.birmingham.ac.uk/index.aspx
"ROR"	https://ror.org/03angcq70

Funders

Funder type

Charity

Results and Publications

Study outputs

Additional files

39925_PIS_Retrospective_v1.0_30Nov20.pdf

39925_PIS_Prospective study and vaccine cohort_v7.0_07Dec21.pdf

39925_PIS_Vaccine cohort_v3.0_07Dec21.pdf

ISRCTN16865769_BasicResults_18Jul24.pdf

Editorial Notes

30/07/2024: Basic results added.
11/04/2023: The following changes were made to the trial record:
1. Total final enrolment added.
2. The overall trial end date was changed from 01/04/2023 to 31/03/2023.
3. The intention to publish date was changed from 31/12/2023 to 31/03/2024.
12/12/2022: The overall end date was changed from 31/12/2022 to 01/04/2023.
30/11/2022: Internal review.
20/05/2021: Trial’s existence confirmed by the National Institute for Health Research (NIHR).