A trial of ibrutinib with rituximab for chronic lymphocytic leukaemia (FLAIR)

Cancer type:

Blood cancers
Chronic leukaemia
Chronic lymphocytic leukaemia (CLL)
Leukaemia

Status:

Open

Phase:

Phase 3

This trial is comparing ibrutinib alongside rituximab with fludarabine, cyclophosphamide, rituximab and venetoclax for chronic lymphocytic leukaemia. This trial is for people who haven’t yet had treatment for their chronic lymphocytic leukaemia (CLL).

Cancer Research UK supports this trial.

More about this trial

Doctors often treat chronic lymphocytic leukaemia (CLL) with the drugs fludarabine, cyclophosphamide and rituximab (FCR). Fludarabine and cyclophosphamide are chemotherapy. Rituximab is a biological therapy called a monoclonal antibody. It seeks out cancer cells by looking for particular proteins. This combination of drugs works but researchers are always looking for ways to improve treatment.

Ibrutinib is a biological therapy called a cancer growth blocker. It stops signals that cancer cells use to divide and grow. We know from research that ibrutinib has helped people whose CLL had continued to grow during treatment or had come back after treatment.

Venetoclax is also a biological therapy. It blocks the functions of a protein found in CLL cells. This causes these cells to die. Another trial is looking at ibrutinib and venetoclax to treat CLL that has come back. The initial results of this trial show that this combination is safe and could help people with CLL. 

The researchers think that ibrutinib with rituximab, or venetoclax, might work well for people with CLL who haven’t yet had treatment. To find this out they want to compare:

  • fludarabine, cyclophosphamide and rituximab (FCR)
  • ibrutinib and rituximab
  • ibrutinib and venetoclax
  • ibrutinib

The aims of this trial are to find out:

  • which treatment is the best for people with CLL that hasn't been treated  
  • how safe these treatments are
  • what are the side effects of these treatments

Who can enter

You may be able to join this trial if you have at least one of the following symptoms:

  • without meaning to, you have lost 10% or more of your body weight in the past 6 months
  • you are very tired and this affects your daily activities
  • you have had a fever for 2 weeks or more but have no sign of an infection
  • you have had night sweats Open a glossary item for more than a month and have no sign of an infection

You must also:

You cannot join this trial if any of these apply:

  • you have already had treatment for your leukaemia
  • your leukaemia has transformed into Richter’s syndrome
  • you have leukaemia in your brain or spinal cord
  • you are to have major surgery within 4 weeks of taking part in this trial
  • you have an infection
  • at least 1 in 5 (20%) of your leukaemia cells have a faulty or missing p53 gene (your doctor can tell you this)
  • you have serious problems with your heart, breathing or digestive system Open a glossary item (the trial team can advise you about this)
  • you have got HIV, hepatitis B or hepatitis C
  • you have had another cancer in the past 3 years apart from successfully treated non melanoma skin cancer and carcinoma in situ of the cervix
  • you have had a stroke in the past 6 months
  • you take other medication that affects body substances called CYP enzymes (your doctor can advise you about this)
  • you are taking medication to thin your blood, such as warfarin
  • you have any other medical condition or mental health problem that the trial team think could affect you taking part
  • you are pregnant or breastfeeding

Trial design

This is a phase 3 trial. The researchers need 1,576 people to join.

It is a randomised trial. The people taking part are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in.

  • group 1 have ibrutinib
  • group 2 have ibrutinib and rituximab
  • group 3 have ibrutinib and venetoclax
  • group 4 have fludarabine, cyclophosphamide and rituximab (FCR)

FLAIR trial diagram
Group 1

Ibrutinib is a capsule. You take 3 capsules every day. You take the capsules 30 minutes before eating or 2 hours after a meal.

You continue to take ibrutinib for 6 years. You might stop and restart treatment during this time. This depends on how your CLL responds. Your doctor will talk to you about this. 

Group 2

Ibrutinib is a capsule. You take 3 capsules every day. You take the capsules 30 minutes before eating or 2 hours after a meal.

You have rituximab as a drip into a vein. You have it every 4 weeks. Each 4 week period is called a cycle of treatment. You have 6 cycles of rituximab.

Group 3

Ibrutinib is a capsule. You take 3 capsules every day. You take the capsules 30 minutes before eating or 2 hours after a meal.

Venetoclax is a tablet. For 8 weeks you take ibrutinib only. You then start taking a small dose of venetoclax. Your doctor will increase the dose of venetoclax each week for the next 5 weeks. You continue treatment for 6 years as long as it is helping.

Group 4

You have rituximab as a drip into a vein. You have it every 4 weeks. Each 4 week period is called a cycle of treatment. You have 6 cycles of rituximab.

You can have fludarabine and cyclophosphamide as tablets or as a drip into a vein. Your doctor will talk to you about what is the best way for you to have them. You have 6 cycles of FCR.

Quality of life

The trial team will ask you to fill out a questionnaire:

  • before you start treatment
  • people in group 2 and 4 fill out a questionnaire after you finish rituximab or FCR 
  • every 6 months for 6 years (starting a year after being put into your group)

The questionnaire will ask about side effects and how you’ve been feeling. This is called a quality of life study.

Blood and bone marrow samples

The researchers will ask for blood samples before you start treatment, 3 months after your last rituximab treatment and 3 months after that. Then you will have blood tests every 6 months if you had ibrutinib, or every year if you had FCR, for another 6 years.

They will also ask for a bone marrow sample Open a glossary item before you start treatment and 3 months after your last rituximab treatment. If you are having ibrutinib they might take another 1 or 2 samples depending on how your CLL responds. 

Hospital visits

You see the doctor to have some tests before taking part in this trial. These tests include:

During treatment you see the doctor every 4 weeks for a physical examination and blood tests. 

People in group 3 have a CT scan at 8 weeks before starting venetoclax. 

Three months after your last rituximab treatment you see the doctor for the same tests you had at the start, apart from the heart trace. You continue to see the doctor every 6 months for another 6 years. At these appointments, you have a physical examination and blood tests.

Side effects

The most common side effects of ibrutinib are:

The most common side effects of venetoclax include:

  • a drop in blood cells causing an increased risk of infection, bruising and bleeding
  • diarrhoea or constipation
  • tiredness
  • feeling or being sick
  • chest infection or urinary infection
  • tumour lysis syndrome

We have information about the side effects of FCR.

Your doctor will talk to you about the possible side effects of treatment before you agree to take part in the trial.

Location

Aberdeen
Airdrie
Aylesbury
Bangor
Basildon
Basingstoke
Birmingham
Blackpool
Boston
Bournemouth
Bradford
Bristol
Cambridge
Canterbury
Cardiff
Carmarthen
Carshalton
Cheltenham
Chichester
Colchester
Coventry
Craigavon
Croydon
Derby
Doncaster
Dudley
Dunfermline
Edinburgh
Gateshead
Gloucester
Grantham
Grimsby
Guildford
Halifax
Harrogate
Huddersfield
Hull
Inverness
Ipswich
Kirkcaldy
Leeds
Leicester
Lincoln
Liverpool
London
Londonderry
Manchester
Middlesbrough
Milton Keynes
Northampton
Nottingham
Orpington
Oxford
Paisley
Poole
Redhill
Rhyl
Romford
Roxburghshire
Salford
Salisbury
Scarborough
Scunthorpe
Sheffield
Southampton
Stoke-on-Trent
Sutton
Sutton Coldfield
Sutton in Ashfield
Swansea
Swindon
Taunton
Torquay
Truro
West Bromwich
Wigan
Worcester
Worthing
Wrexham
York

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Professor Peter Hillmen

Supported by

Cancer Research UK 
Abbvie
Experimental Cancer Medicine Centre (ECMC)
Janssen Pharmaceuticals
University of Leeds

Other information

This is Cancer Research UK trial number CRUK/12/037.

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

10515

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Charlie took part in a trial to try new treatments

A picture of Charlie

“I think it’s really important that people keep signing up to these type of trials to push research forward.”

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