Adults with Acute Myeloid Leukaemia or High-Risk Myelodysplastic Syndrome (AML19)

ISRCTN	ISRCTN78449203
DOI	https://doi.org/10.1186/ISRCTN78449203
EudraCT/CTIS number	2014-002195-90
Secondary identifying numbers	SPON1334-04

Submission date: 30/09/2014
Registration date: 08/12/2014
Last edited: 02/04/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-different-treatments-for-acute-myeloid-leukaemia-and-high-risk-myelodysplastic
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-treatment-for-acute-promyelocytic-leukaemia-aml-19

Study website

Contact information

Prof Nigel Russell
Scientific

Nottingham University
Haematology Department
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Email	nigel.russell@nottingham.ac.uk

Study information

Study design	Randomized controlled open-label phase III trial, factorial design
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Patient information sheets are provided through the patients hospital setting
Scientific title	Adults with Acute Myeloid Leukaemia or High-Risk Myelodysplastic Syndrome (AML19): a randomised, controlled, open label Phase III trial
Study acronym	AML19
Study hypothesis	Current study hypothesis as of 25/02/2021: Primary Objective: To compare overall survival in patient groups of differing risk status by assessing time from randomisation into particular arms of the study until death from any cause Secondary Objectives: 1. To assess achievement of complete remission (CR) after treatment in all patient groups by calculating time of randomisation until time of first CR 2.To assess duration of CR by reviewing time from first CR to first relapse, and see if rate of relapse varies by treatment group 3. To assess the toxicities experienced in each course of treatment in all patient groups 4. To evaluate the safety and efficacy of Midostaurin in patients with a FLT3 mutation who have received DA chemotherapy combined with Gemtuzumab Ozogamicin (Mylotarg) 5. To assess quality of life in all patient groups Exploratory Objectives: To evaluate the therapeutic relevance of morphological, cytogenetic, molecular-genetic (genomic) and immunophenotypic assessments, in particular: 1. The relevance of the molecular and immunophenotypic detection of minimal residual disease 2. To associate molecular genotype (genomics) with clinical outcome 3. To store excess diagnostic material for future research Previous study hypothesis: For patients with acute myeloid leukaemia (AML) the aims of the AML19 trial are: 1. To compare four induction chemotherapy schedules (namely DA + Mylotarg (3mg/m2) or DA + Mylotarg (3mg/m2 x2, maximum 5mg per day)versus FLAG-Ida + Mylotarg (3mg/m2) or FLAG-Ida + Mylotarg (3mg/m2 x2, maximum 5mg per day)) in patients who are not known at entry to have adverse cytogenetics 2. For patients receiving FLAG-Ida to compare one or two courses of HDAC consolidation versus no further treatment 3. Patients with FLT3 mutations may enter the AML19 pilot trial 4. To assess the value of Ganetespib in patients who lack a FLT3 mutation and are not high risk 5. In high risk patients, and those known to have adverse cytogenetics at entry, to compare novel treatment, CPX-351 vs FLAG-Ida 6. In high risk patients who have received 2 courses of FLAG-Ida induction, to evaluate in a non randomised fashion the combination of Fludarabine + CPX-351 7. In high risk patients, to evaluate, the value of allogeneic stem cell transplantation (SCT), from sibling or alternative donors 8. To assess the clinical value of minimal residual disease monitoring for patients overall survival For patients with APL the aims of the AML19 trial are: 1. To evaluate the Idarubicin based, AIDA Schedule 2. Endpoints for Patients who have non-APL AML. The main endpoints for each comparison will be: 2.1. Overall survival (OS) 2.2. Complete remission (CR) achievement and reasons for failure (for induction questions) 2.3. Duration of remission, relapse rates and deaths in first CR 2.4. Toxicity, both haematological and non-haematological 2.5. Quality of life for patients in the disease monitoring randomisation 2.6. Supportive care requirements (and other aspects of health economics)
Ethics approval(s)	Wales REC 3, 12/08/2014, ref. 14/WA/1056
Condition	Acute myeloid leukaemia and myelodysplastic syndrome
Intervention	Current interventions as of 25/02/2021: Patients with CD33 positive de novo AML are randomised in a 1:1 ratio between DA chemotherapy and one dose of Mylotarg (given at a dose of 3 mg/m² on Day 1 of Course 1), and DA chemotherapy and two doses of Mylotarg (given at a dose of 3 mg/m² up to maximum of 5 mg, on Day 1 and Day 4 of course 1). Patients who have a FLT3 mutation identified by the AML19 laboratory will have Midostaurin added to their treatment regimen, at a dose of 50 mg PO twice daily (Days 11-24 of Course 1). All patients have DA chemotherapy alone in Course 2, and recieve high dose Ara-C as consolidation treatment in Courses 3 and 4. Those who recieve Midostaurin will take this on Days 9-22 of Course 1, and Days 8-21 of Courses 3 and 4. Patients on Midostaurin will then have Midostaurin maintenance therapy for 12 cycles of 28 days. If a patient is identified to be high-risk at any time, they should be taken off-trial and FLAG-Ida/transplant is recommended. Previous interventions: The AML19 trial looks to build upon previous trials in AML. It is known that the condition can present with one of two subtypes, and this is taken into account in the trial design. In the majority of patients (those who do not have the APL-subtype), the trial looks to refine the current standard of care (which is a combination of drugs called DA) by asking a number of questions: 1. To compare two drug combinations (Daunorubicin/Ara-C DA vs Fludarabine/Ara-C/G-CSF/Idarubicin FLAG-Ida) to see which gives better survival 2. To identify the best way of giving the drug Mylotarg in addition to chemotherapy either at a single dose of 3mg/m2 or in 2 doses of either 3mg/m2 or 5mg whichever is smaller. (This randomisation will only be available to patients who are suitable to receive Mylotarg). 3. In patients who receive FLAG-Ida, to work out the optimal number of courses of treatment. In particular, how much if any consolidation treatment with Ara-C is required a randomisation between 0,1 and 2 courses of consolidation 4. To see if inhibiting a protein called HSP-90 with a drug called Ganetespib will improve outcomes 5. For poor risk patients, to see if a new drug called CPX-351 is any better than standard of care, which is FLAG-Ida 6. In patients who fail following 2 courses of FLAG-Ida (and so would not be suitable for further FLAG-Ida treatment) to evaluate a combination of Fludarabine and CPX-351 7. To evaluate whether a stem-cell transplant (e.g a bone marrow transplant) from either a matched sibling or unrelated donor can improve outcomes 8. To see whether monitoring patients bone marrow and blood sequentially can improve outcomes by successfully predicting patients who are likely to relapse, and what effect his has on quality of life. Additionally patients who are found to have a FLT-3 mutation will be able to access the AML19 Pilot Trial of Ponatinib. In patients with the APL subtype we will continue to assess the real-world effectiveness of standard of care, which is a combination of drugs called AIDA (ATRA plus Idarubicin), and to allow patients to access residual disease monitoring.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Gemtuzumab ozogamicin, daunorubicin, cytarabine, midostaurin
Primary outcome measure	Current primary outcome measure as of 25/02/2021: Overall survival in patient groups of differing risk status by measuring time from randomisation into particular arms of the study until death from any cause Previous primary outcome measure: To be assessed at the end of trial. The AML19 trial looks to build upon previous trials in AML. It is known that the condition can present with one of two subtypes, and this is taken into account in the trial design. In the majority of patients (those who do not have the APL-subtype), the trial looks to refine the current standard of care (which is a combination of drugs called DA) by asking a number of questions: 1. To compare two drug combinations (Daunorubicin/Ara-C DA vs Fludarabine/Ara-C/G-CSF/Idarubicin FLAG-Ida) to see which gives better survival 2. To identify the best way of giving the drug Mylotarg in addition to chemotherapy either at a single dose of 3mg/m2 or in 2 doses of either 3mg/m2 or 5mg whichever is smaller. (This randomisation will only be available to patients who are suitable to receive Mylotarg). 3. In patients who receive FLAG-Ida, to work out the optimal number of courses of treatment. In particular, how much if any consolidation treatment with Ara-C is required a randomisation between 0,1 and 2 courses of consolidation 4. To see if inhibiting a protein called HSP-90 with a drug called Ganetespib will improve outcomes 5. For poor risk patients, to see if a new drug called CPX-351 is any better than standard of care, which is FLAG-Ida 6. In patients who fail following 2 courses of FLAG-Ida (and so would not be suitable for further FLAG-Ida treatment) to evaluate a combination of Fludarabine and CPX-351 7. To evaluate whether a stem-cell transplant (e.g a bone marrow transplant) from either a matched sibling or unrelated donor can improve outcomes 8. To see whether monitoring patients bone marrow and blood sequentially can improve outcomes by successfully predicting patients who are likely to relapse, and what effect his has on quality of life. Additionally patients who are found to have a FLT-3 mutation will be able to access the AML19 Pilot Trial of Ponatinib. In patients with the APL subtype we will continue to assess the real-world effectiveness of standard of care, which is a combination of drugs called AIDA (ATRA plus Idarubicin), and to allow patients to access residual disease monitoring.
Secondary outcome measures	Current secondary outcome measures as of 01/03/2021: 1. Achievement of complete remission (CR) after treatment in all patient groups by measuring time from randomisation until time of first CR 2. Duration of CR by measuring time from first CR to first relapse 3. Rate of relapse by treatment group measured using number of events of relapse following CR recorded in participant notes between randomisation and the end of the study 4. Toxicities experienced in each course of treatment in all patient groups measured using number of events of toxicity recorded in participant notes between randomisation and the end of the study 5. Safety and efficacy of Midostaurin in patients with a FLT3 mutation who have received DA chemotherapy combined with Gemtuzumab Ozogamicin (Mylotarg) measured using number of adverse events recorded in participant notes between randomisation and the end of the study and overall survival from randomisation until death from any cause 6. Quality of life in all patient groups measured using the EORTC QLQ-C30 Version 3 questionnaire at baseline, prior to C2 (~6 weeks), 3, 6, 9, and 12 months after randomisation Previous secondary outcome measures as of 25/02/2021: 1. Achievement of complete remission (CR) after treatment in all patient groups by measuring time from randomisation until time of first CR 2. Duration of CR by measuring time from first CR to first relapse 3. Rate of relapse by treatment group measured using number of events of relapse following CR recorded in participant notes between randomisation and the end of the study 4. Toxicities experienced in each course of treatment in all patient groups measured using number of events of toxicity recorded in participant notes between randomisation and the end of the study 5. Safety and efficacy of Midostaurin in patients with a FLT3 mutation who have received DA chemotherapy combined with Gemtuzumab Ozogamicin (Mylotarg) measured using number of adverse events recorded in participant notes between randomisation and the end of the study and overall survival from randomisation until death from any cause 6. Quality of life in all patient groups Previous secondary outcome measures: To be reviewed at the end of the trial. In addition to the main clinical questions above, the trial will collect a lot of data on a well characterised group of patients. This will enable the following questions to be addressed: 1. What is the relevance of detecting minimal residual disease using one of two methods (molecular and immunophenotypic) 2. Are there biomarkers or other molecular (laboratory) measurements that correlate with clinical outcome Consent will be taken to store any excess diagnostic material for future research that will inform future trials.
Overall study start date	01/01/2015
Overall study end date	31/07/2023

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	16 Years
Upper age limit	60 Years
Sex	Both
Target number of participants	2150 (1888 patients recruited prior to the COVID-19 pandemic, 250 to be recruited under the new protocol)
Total final enrolment	1033
Participant inclusion criteria	Current participant inclusion criteria as of 25/02/2021: 1. One of the forms of CD33 positive (any level), favourable, standard risk or unknown cytogenetics de novo AML as defined by theWHO Classification 2. WHO performance status 0-2 3. Considered suitable for intensive chemotherapy 4. Aged 16 to 60 years with the following caveats: 4.1. If intensive therapy is considered a suitable option those aged >60 years are eligible 4.2. To receive midostaurin: aged ≥18 years 5. A negative pregnancy test within 2 weeks prior to trial entry in WOCBP to be repeated throughout the trial prior to each course of protocol treatment 6. Sexually active participants must agree to use an adequate and medically accepted method of contraception throughout the study, and for 6 months following treatment (female participants receiving Mylotarg should continue for 7 months following treatment), if they, or their sexual partners, are women of childbearing potential (WOCBP) 7. Written informed consent provided 8. Patients must have Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5 × upper limit of normal (ULN) and bilirubin ≤2 × ULN 9. To receive midostaurin: FLT3-TKD or FLT3-ITD mutation detected by the central laboratory in Cardiff Previous participant inclusion criteria: AML Patients: 1. They have one of the forms of acute myeloid leukaemia as defined by the WHO Classification (Appendix A) this can be any type of de novo or secondary AML or high risk Myelodysplastic Syndrome (defined as >10% bone marrow blasts) 2. Patients with acute promyelocytic leukaemia (APL) are eligible and should be entered into the randomisations specifically for APL (see Section 9) 3. They are considered suitable for intensive chemotherapy 4. They should normally be 18 years up to the age of 60, but patients over this age are eligible if = intensive therapy is considered a suitable option 5. The serum creatinine should be ≤ 1.5 × ULN (upper limit of normal) 6. Patients eligible for the Mylotarg randomisation must have Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤2.5 × ULN and bilirubin ≤2.× ULN (Note: Patients who do not comply with the liver inclusion criteria are eligible to enter the trial but will be excluded from the Mylotarg randomisation) 7. Sexually mature males must agree to use an adequate and medically accepted method of contraception throughout the study if their sexual partners are women of child bearing potential (WOCBP). Similarly women must agree to adequate contraceptive measures. This applies to APL and AML patients. In both males and females these measures must be in place for at least 30 days after the last administration of ganetespib 8. They have given written informed consent APL Patients: 1. They have provided signed written informed consent (PIS 3) 2. They have a morphological diagnosis of APL (if cytogenetic or molecular diagnosis is not confirmed patients will transfer to the non-APL treatments) 3. They should be over 18 years 4. They have WHO performance status 0-2 5. Their serum total bilirubin is < 2.0 mg/dL (≤51 µmol/L) 6. Their serum creatinine is < 3.0 mg/dL (< 260 µmol/L)
Participant exclusion criteria	Current participant exclusion criteria as of 25/02/2021: 1. Patients with APL, secondary AML, therapy-related AML, high-risk myelodysplastic syndrome with <20% bone marrow blasts, or de novo AML with known adverse risk cytogenetics 2. Patients who have previously received cytotoxic chemotherapy for AML. Hydroxycarbamide, or similar low-dose therapy, to control the white count prior to initiation of intensive therapy is not an exclusion. 3. Blast transformation of chronic myeloid leukaemia (CML) 4. Concurrent active malignancy requiring treatment 5. Pregnant or lactating Previous participant exclusion criteria: Patients are not eligible for the AML arms of the AML19 trial if: 1. They have previously received cytotoxic chemotherapy for AML. [Hydroxycarbamide, or similar low-dose therapy, to control the white count prior to initiation of intensive therapy is not an exclusion.] 2. They have received demethylation therapy for AML or high risk MDS defined as marrow blasts >10%. Patients treated for lower risk MDS who progress to AML are eligible 3. They are in blast transformation of chronic myeloid leukaemia (CML) 4. They have a concurrent active malignancy requiring treatment 5. They are pregnant or lactating 6. The physician and patient consider that intensive therapy is not an appropriate treatment option 7. Known infection with Human Immunodeficiency Virus (HIV) 8. Patients with AST or ALT more than 2.5 times the local upper limit of normal or Bilirubin more than twice upper limit of normal, are not eligible for the Mylotarg randomisations For Ganetespib randomisation there are specific cardiac exclusions: 1. A myocardial infarction within 12 months 2. Uncontrolled angina within 6 months 3. Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless an echocardiogram (ECHO) or Multiple Gated Acquisition Scan (MUGA) performed either within 1 month prior to study screening or during screening results in a left ventricular ejection fraction (LVEF) that is ≥ 45% (or institutional lower limit of normal value) 4. Diagnosed or suspected congenital long QT syndrome. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes [TdP]) or any history of arrhythmia will be discussed with the Clinical Coordinator/Safety Physician prior to patients entry into the study 5. Prolonged QTcF interval on pre-entry ECG (≥450 ms) 6. Any history of second or third degree heart block (may be eligible if the patient currently has a pacemaker 7. Heart rate <50/minute on pre-entry ECG 8. Uncontrolled hypertension 9. Obligate need for a cardiac pacemaker 10. Complete left bundle branch block 11. Atrial fibrillation APL Patients: 1. They are aged < 18 2. They have an active malignancy requiring treatment at time of study entry 3. There is a lack of subsequent diagnostic confirmation of PML-RARA fusion at molecular level 4. Known infection with Human Immunodeficiency Virus (HIV) 5. Significant arrhythmias, ECG abnormalities or neuropathy are apparent 6. Severe uncontrolled pulmonary or cardiac disease is apparent 7. They are pregnant or lactating
Recruitment start date	01/01/2015
Recruitment end date	29/10/2021

Locations

Countries of recruitment

Denmark
England
New Zealand
Northern Ireland
Scotland
United Kingdom
Wales

Study participating centres

Nottingham University

Nottingham
NG5 1PB
United Kingdom

Aalborg University Hospital

Dept. of Haematology
Clinical Trial Unit
Moelleparkvej 4
Aalborg
DK-9000
Denmark

Aarhus University Hospital

Tage-Hansens Gade 2
Aarhus
8000
Denmark

Aberdeen Royal Infirmary

Haemotology Day Unit
Ward 307
Foreseter Hill
Aberdeen
AB25 2ZN
United Kingdom

Addenbrookes University Hospital

Addenbrookes Hospital
Cambridge University Hospitals NHS Foundation
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Aintree University Hospital

Aintree Hospital
Lower Lane
Liverpool
L9 7AL
United Kingdom

Arrowe Park Hospital

Arrowe Park Road
Upton
Wirral
CH49 5PE
United Kingdom

Auckland Hospital

2 Park Road
Grafton
Auckland
1023
New Zealand

Basingstoke and North Hampshire Hospital

Aldermaston Road
Basingstoke
RG24 9NA
United Kingdom

Beatson WOS Cancer Centre

Cancer Research UK Clinical Trials Unit
West of Scotland Beatson Cancer Centre, Level 0
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Belfast City Hospital

51 Lisburn Road
Belfast
BT9 7AB
United Kingdom

Birmingham Heartlands Hospital

Bordesley Green East
Birmingham
B9 5SS
United Kingdom

Blackpool Victoria Infirmary

Blackpool Victoria Hospital
Whinney Heys Road
Blackpool
FY3 8NR
United Kingdom

Bradford Royal Infirmary

Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Bristol Haematology and Oncology Centre

Horfield Road
Bristol
BS2 8ED
United Kingdom

Castle Hill Hospital

Queens Centre for Oncology & Haematology
Castle Road
Cottingham
HU16 5JQ
United Kingdom

Cheltenham General Hospital

Sandford Road
Cheltenham
GL53 7AN
United Kingdom

Chesterfield Royal Hospital

Calow
Chesterfield
S44 5BL
United Kingdom

Christchurch Hospital

Riccarton Road
Christchurch
8011
New Zealand

The Christie Haematology and Transplant Unit

Wilmslow Road
Withington
Mancester
M20 4BX
United Kingdom

Churchill Hospital

Cancer and Haematology Centre
Level 2
Old Road
Headington
Oxford
OX3 9EP
United Kingdom

Clatterbridge Cancer Centre

The Royal Liverpool Hospital
Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom

Conquest Hospital

Sussex Cancer Research Team
St Anne’s House
729 The Ridge
East Sussex
TN37 7PT
United Kingdom

Countess of Chester Hospital

Liverpool Road
Chester
Cheshire
CH2 1UL
United Kingdom

Croydon University Hospital

Research Office
1st Floor Woodcroft Wing
London Road
Croydon
CR7 7YE
United Kingdom

Derriford Hospital

Derriford Road
Plymouth
PL6 8DH
United Kingdom

Doncaster Hospital

Doncaster & Bassetlaw Hospitals NHS Foundation Trust
Armthorpe Road
Doncaster
DN2 5LT
United Kingdom

Dunedin Hospital

Dunedin Hospital
Southern Blood and Cancer Service
201 Great King Street
Dunedin
9016
New Zealand

Eastbourne District General Hospital

Kings Drive
Eastbourne
BN21 2UD
United Kingdom

Forth Valley Royal Hospital

Oncology Department
Stirling Road
Larbet
FK5 4WR
United Kingdom

Freeman Hospital

Haematology Research
Level 2 NCCC
Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle Upon Tyne
NE7 7DN
United Kingdom

Glan Clwyd Hospital

Bodelwyddan
Denbighshire
LL18 5UJ
United Kingdom

Gloucestershire Royal Hospital

Great Western Road
Gloucester
GL1 3NN
United Kingdom

Guy's Hospital

Guy's and St Thomas NHS Trust
Great Maze Pond
Clinical Haematology
4th Floor Southwark Wing
London
SE1 9RT
United Kingdom

Herlev and Gentofte Hospital

Herlev Ringvej 75
Herlev
2730
Denmark

Hillingdon Hospital

Pield Heath Road
Uxbridge
UB8 3NN
United Kingdom

Ipswich Hospital

Heath Road
Ipswich
IP4 5PD
United Kingdom

James Cook University Hospital

NIHR- Clinical Research Network North East and Cumbria
Department of Radiotherapy and Oncology
Marton Road
Middlesbrough
TS4 3BW
United Kingdom

James Paget Hospital

Lowestoft Road
Gorleston-on-Sea
Great Yarmouth
Norfolk
NR31 6LA
United Kingdom

Kettering General Hospital

Rothwell Road
Kettering
NN16 8U2
United Kingdom

Leicester Royal Infirmary

The Hope Clinical Trials Unit
Level 2 Osborne Building
Infirmary Square
Leicester
LE1 SWW
United Kingdom

Lewisham

Lewisham High St
London
SE13 6LH
United Kingdom

Lincoln County Hospital

Greetwell Road
Lincoln
LN2 5QY
United Kingdom

Manchester Royal Infirmary

Oxford Road
Manchester
M13 9W
United Kingdom

Medway Maritime Hospital

Windmill Road
Gillingham
ME7 5NY
United Kingdom

Milton Keynes Hospital

Standing Way
Eaglestone
Milton Keynes
MK6 5LD
United Kingdom

Monklands Hospital

Monkscourt Ave
Airdrie
ML6 0JS
United Kingdom

Musgrove Park Hospital

Parkfield Drive
Taunton
TA1 5DA
United Kingdom

New Cross Hospital

Wednesfield Road
Wolverhampton
WV10 0QP
United Kingdom

New Victoria Hospital

The New Victoria Ach
Grange Road
Glasgow
G42 9LF
United Kingdom

Ninewells Hospital and Medical Centre

James Arrott Drive
Dundee
DD1 9SY
United Kingdom

Norfolk and Norwich University Hospital

Colney Lane
Norwich
NR4 7UY
United Kingdom

Northampton General Hospital

Haematology Day Unit
Cliftonville
Northampton
NN1 5BD
United Kingdom

Centre for Clinical Haematology

Nottingham University Hospitals NHS Trust
City Hospital Campus
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Odense University Hospital

Hæmatologisk Forskningeenhed HFE-X
Kløvervænget 10,12 sal
Odense
5000
Denmark

Palmerston North Hospital

Regional Cancer Treatment Service
Department of Clinical Haematology
Private Bag 11036
Manawatu Mail Centre
Palmerston North
4442
New Zealand

Pinderfields General Hospital

Research Team
Rowan House
Aberford Road
Wakefield
WF1 4DG
United Kingdom

Poole Hospital

Poole Hospital NHS Trust
Longfleet Road
Poole
BH15 2JB
United Kingdom

Queen Alexandra Hospital

Haematology and Oncology Research
Cosham
Portsmouth
P06 3LY
United Kingdom

Queen Elizabeth Hospital

Edgbaston
Birmingham
B15 2TH
United Kingdom

Queen Elizabeth Hospital

Stadium Road
London
SE18 4QH
United Kingdom

Queens Hospital

9 Cancer Clinical Trials Unit
Rom Valley Way
Romford
RM7 0AG
United Kingdom

Raigmore Hospital

Old Perth Road
Inverness
IV2 3UJ
United Kingdom

Rigshospitalet

Blegdamsvej
Clinical Trial Team (KAT)- 4042
Copenhagen
2100
Denmark

Roskilde Sygehus

Hæmatologisk Afdeling
Klinisk Forskningsenhed
Indgang 27 A, 1. Sl
Roskilde
4000
Denmark

Rotherham General Hospital

Moorgate Road
Rotherham
S60 2UD
United Kingdom

Royal Berkshire Hospital

London Road
Reading
RG1 5AN
United Kingdom

Royal Bournemouth Hospital

Castle Lane East
Bournemouth
BH77DW
United Kingdom

Royal Cornwall Hospital

Haematology department
Treliske
Truro
TR1 3LJ
United Kingdom

Royal Derby Hosptial

Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Royal Devon and Exeter Hospital

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

Royal Hallamshire Hosptial

Glossop Road
Sheffield
S10 2JF
United Kingdom

Royal Marsden Hospital

The Royal Marsden NHS Foundation Trust
Downs Road
Sutton
SM2 5PT
United Kingdom

Royal Oldham Hospital

Marjorie Lees Unit, Room 31
Rochdale Road
Oldham
OL1 2JH
United Kingdom

Royal Stoke University Hospital

Newcastle Road
Stoke-on-Trent
ST4 6QG
United Kingdom

Royal Surrey County Hospital

St Lukes Cancer Centre
Royal Surrey County Hospital NHS Foundation Trust
Egerton Road
Guildford
GU2 7XX
United Kingdom

Royal United Hospitals

Royal United Hospitals NHS Foundation Trust
Dept A14
Combe Park
Bath
BA1 3NG
United Kingdom

Russells Hall Hospital

Pensnett Road
Dudley
DY1 2HQ
United Kingdom

Salford Royal Hospital

Oncology Research Department
Summerfield House
Salford Royal NHS Foundation Trust
Stott Lane
Salford
M6 8HD
United Kingdom

Salisbury District Hospital

Haematology Department, Pathology
Salisbury NHS Foundation Trust
Salisbury
SP2 8BJ
United Kingdom

Sandwell Hospital

Lyndon
West Bromwich
B71 4HJ
United Kingdom

Singleton Hospital

Sketty Lane
Swansea
SA2 8QA
United Kingdom

Southampton General Hospital

University Hospital Southampton NHS Foundation Trust
Tremona Road
Southampton
S016 6YD
United Kingdom

St Bartholomew's Hospital

West Smithfield
London
EC1A 7BE
United Kingdom

St George's University Hospital

Blackshaw Road
London
SW17 0QT
United Kingdom

St Helens Hospital

St Helens and Knowsley NHS Trust
Warrington Road
Prescot
Merseyside
L35 5DR
United Kingdom

St James University Hospital

Level 3 Bexley Wing
Becket Street
Leeds
LS9 7TF
United Kingdom

St Richard's Hospital

Spitalfield Lane
Chichester
PO19 6SE
United Kingdom

Stoke Mandeville Hospital

Mandeville Road
Aylesbury
HP21 8AL
United Kingdom

Sunderland Royal Hospital

Kayll Road
Sunderland
SR4 7TP
United Kingdom

Torbay District General Hospital

Lawes Bridge
Torquay
TQ2 7AA
United Kingdom

University College London Hospitals

Haematology CCTU
1st Floor Central
250 Euston Road
London
NW1 2PG
United Kingdom

University Hospital Ayr

Dalmellington Road
Ayr
KA6 6DX
United Kingdom

University Hospital Coventry

Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

University Hospital Crosshouse

Kilmarnock Road
Crosshouse
Kilmarnock
KA2 0BE
United Kingdom

University Hospital of Wales

Heath Park
Cardiff
CF14 4XW
United Kingdom

Victoria Hospital

Hayfield Road
Kirkcaldy
Fife
KY2 5AH
United Kingdom

Waikato Hospital

Waikato District Health Board
Pembroke Street
Private Bag 3200
Hamilton
3240
New Zealand

Western General Hospital

Haematology Department
Crewe Road South
Edinburgh
EH4 2XU
United Kingdom

Worcestershire Royal Hospital

Charles Hastings Way
Worcester
WR5 1DD
United Kingdom

Worthing Hospital

Lyndhurst Road
Worthing
BN11 2DH
United Kingdom

Wycombe Hospital

Queen Alexandra Road
High Wycombe
HP11 2TT
United Kingdom

York Hospital

Cancer Research Team, Research, and Development
Learning and Research Centre (LARC)
Wigginton Road
York
YO31 8HE
United Kingdom

Ysbyty Gwynedd

Penrhosgarnedd
Bangor
LL57 2PW
United Kingdom

Sponsor information

Cardiff University (UK)
University/education

Research, Innovation & Enterprise Services, 7th Floor, 30-36 Newport Road
Cardiff
CF10 3XQ
Wales
United Kingdom

Email	resgov@cardiff.ac.uk
"ROR"	https://ror.org/03kk7td41

Funders

Funder type

Charity

Cancer Research UK
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	12/05/2023	15/05/2023	Yes	No
HRA research summary		26/07/2023	No	No
Results article	12/01/2024	15/01/2024	Yes	No

Editorial Notes

02/04/2024: Total final enrolment added.
15/01/2024: Publication reference added.
15/05/2023: Publication reference added.
05/11/2021: The recruitment end date has been changed from 31/10/2021 to 29/10/2021.
01/03/2021: Recruitment for this study is no longer paused as of 04/11/2020 and the following changes have been made:
1. The target number of participants has been changed from 3000 to 2150 (1888 patients recruited prior to the COVID-19 pandemic, 250 to be recruited under the new protocol).
2. Total target enrolment has been changed from 3000 to 2150.
3. The secondary outcome measures have been updated.
26/02/2021: The trial participating centres have been added.
25/02/2021: The following changes have been made:
1. The recruitment end date has been changed from 01/01/2021 to 31/10/2021.
2. The overall trial end date has been changed from 01/01/2021 to 31/07/2023.
3. The study hypothesis has been updated.
4. The interventions been updated.
5. The primary outcome measure has been updated.
6. The secondary outcome measures have been updated.
7. The drug name(s) have been added.
8. The trial website has been added.
9. The participant inclusion criteria have been updated.
10. The participant exclusion criteria have been updated.
11. The countries of recruitment "Denmark" and "New Zealand" have been added.
01/05/2020: Recruitment for this study has been paused.
17/03/2020: Internal review.
27/04/2016: Plain English summary link added.