FLAIR: a randomised phase 3 trial comparing treatments containing ibrutinib with standard first treatment for chronic lymphocytic leukaemia (CLL)
The aim of this trial is to see if ibrutinib-containing treatments work better than the standard treatment for chronic lymphocytic leukaemia (CLL) .
Note that this trial is now only recruiting people with CLL who have 'high-risk’ genetic changes (genetic changes that mean the CLL is likely to be faster-growing).
Trial aim and background
CLL is often treated with a combination called FCR. This is fludarabine and cyclophosphamide chemotherapy with the antibody treatment rituximab.
Ibrutinib is already used to treat CLL that has come back after treatment (relapsed). Now researchers want to test it in CLL at an earlier stage. They are testing it on its own, with rituximab or with venetoclax. The researchers want to find out:
- which drug combination works better as a first treatment for CLL
- more about the side effects of ibrutinib
- whether ibrutinib affects quality of life compared to FCR.
This is a randomised trial. Participants are randomised to one of three groups:
- standard treatment of fludarabine, cyclophosphamide and rituximab
- ibrutinib alone
- ibrutinib and venetoclax.
Another group testing ibrutinib and rituximab is now closed to recruitment as enough people have already been recruited for that group.
You can’t choose which treatment you have and neither can your doctor. You are told what treatment you are having and given information about it.
Ibrutinib is a cell signal blocker. It blocks signals that encourage leukaemia cells to grow. Rituximab is a monoclonal antibody. Venetoclax targets and blocks a protein important for survival of some lymphoma cells, called Bcl-2.
- If you are in the FCR group, you have rituximab every 4 weeks for 6 months. In addition, you have cyclophosphamide and fludarabine chemotherapy as tablets or intravenously.
- If you are in the ibrutinib alone group, you take ibrutinib capsules every day for up to 6 years.
- If you are in the ibrutinib and venetoclax group, you take ibrutinib capsules every day for up to 6 years. You take venetoclax every day from week 9 onwards for up to 6 years. The dose of venetoclax is gradually increased over the first few weeks of treatment.
If you are in one of the ibrutinib-containing groups, your treatment will stop if levels of lymphoma fall to a very low level in the first three years of treatment. If the levels of lymphoma rise again within six years, the treatment will be started again. Treatment can continue for up to a total of 6 years of treatment.
After 6 years, people who have received ibrutinib as part of the FLAIR trial will be eligible to enter a trial called STATIC if they would like to. STATIC is comparing continuous ibrutinib treatment with intermittent ibrutinib treatment. It is due to open in September 2021.
You have regular blood tests during treatment and then 6 monthly or yearly for several years afterwards. You may need a bone marrow test before you start treatment and everyone will need a bone marrow test at nine months after entering the trial. If you are taking ibrutinib, you will need another bone marrow test when you finish treatment with ibrutinib.
Who can enter
If you are an adult with symptomatic CLL requiring treatment and a faulty or missing part of the TP53 gene and are fit enough for treatment you may be eligible to apply for this trial.
Locations
Recruitment is taking place in the following UK locations:
- Aberdeen
- Abergavenny
- Airdrie
- Aylesbury
- Ayr
- Bangor
- Basildon
- Basingstoke
- Bath
- Belfast
- Birmingham
- Blackpool
- Boston
- Bournemouth
- Bradford
- Bristol
- Cambridge
- Cardiff
- Carshalton
- Cheltenham
- Chester
- Chichester
- Colchester
- Coventry
- Craigavon
- Croydon
- Derby
- Doncaster
- Dorchester
- Dudley
- Dunfermline
- Edinburgh
- Exeter
- Gateshead
- Glasgow
- Gloucester
- Grantham
- Grimsby
- Guildford
- Halifax
- Harrogate
- Hemel Hempstead
- High Wycombe
- Huddersfield
- Hull
- Inverness
- Ipswich
- Kettering
- Kidderminster
- Kilmarnock
- Kirkcaldy
- Lancaster
- Leeds
- Leicester
- Lincoln
- Liverpool
- London
- Londonderry
- Manchester
- Middlesbrough
- Middlesex
- Milton Keynes
- Newport (IOW)
- Northallerton
- Northampton
- Nottingham
- Nuneaton
- Oldham
- Oxford
- Paisley
- Peterborough
- Plymouth
- Poole
- Portsmouth
- Redditch
- Redhill
- Romford
- Rotherham
- Roxburghshire
- Salford
- Salisbury
- Sheffield
- Shrewsbury
- Southampton
- Stoke-on-Trent
- Sutton
- Sutton Coldfield
- Sutton in Ashfield
- Swansea
- Taunton
- Torquay
- Truro
- Watford
- West Bromwich
- Wigan
- Winchester
- Worcester
- Worthing
- Wrexham
- York
Further information
More information about what treatments are involved, the criteria you must meet in order to take part in the trial and where this trial is taking place are available at Cancer Research UK.
Lymphoma Action are not able to refer people to specific trials. If you are interested in taking part in this trial we recommend that you print the trial summary and discuss it with your medical team. They can advise you on whether you might be eligible for the trial and how you can take part based on your individual circumstances.