A trial of ibrutinib with rituximab for chronic lymphocytic leukaemia (FLAIR)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Status:
Phase:
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 
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 targeted cancer drug 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 targeted cancer drug. 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
There are 2 groups in this trial:
- standard risk group - this group is now closed to recruitment
- genetically high risk group
Which group you are in and the treatment you have depends on the results of test on some of your leukaemia cells. This test looks for a faulty or missing part of a gene called T53.
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
When you agree to join the trial your leukaemia cells are tested to find out if they have a faulty or missing part of a gene called TP53.
There are 2 groups in this trial. Which group you go into depends on the results of this test.
The standard risk group is for people who don't have a faulty or missing part of the gene called TP53. Please note that recruitment to this group is now closed.
The genetically high risk group is for people who do have a faulty or missing part of the TP53 gene.
You may be able to join either group 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 for more than a month and have no sign of an infection
You must also:
- have chronic lymphocytic leukaemia (CLL) that needs treating
- be well enough to be up and about for at least half the day (performance status 0, 1 or 2)
- have satisfactory blood test results
- be able to swallow tablets or capsules
- be willing to use reliable contraception during treatment and for a year afterwards if there is any chance you or your partner could become pregnant
- be between 18 and 75 years old (for people in the genetically high risk pathway there is no upper age limit)
People in the standard risk group must also be fit enough to have treatment with fludarabine, cyclophosphamide and rituximab (FCR).
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
- 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 (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 are taking medication for high blood pressure called an ACE inhibitor such as ramipril, lisinopril or any medication that contains an ACE inhibitor. You might be able to join if your doctor can change your medication to one that isn't an ACE inhibitor or doesn't contain an ACE inhibitor.
- 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
As well as the above for people in the genetically high risk group you cannot take part if have had a severe allergic reaction to certain monoclonal antibodies. Your doctor can tell you about this.
Trial design
This is a phase 3 trial. There are 2 groups in this trial:
- standard risk group - this group is now closed to recruitment
- genetically high risk group
The researchers need 1,516 people to join the standard risk group. And 64 people to join the genetically high risk group.
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.
Standard risk group (closed to recruitment)
There are 4 treatment groups:
- group 1 have ibrutinib - closed
- group 2 have ibrutinib and rituximab - closed
- group 3 have ibrutinib and venetoclax - closed
- group 4 have fludarabine, cyclophosphamide and rituximab (FCR) - closed
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.
Genetically high risk group
There are 2 treatment groups:
- ibrutinib
- ibrutinib and venetoclax
You have ibrutinib and venetoclax as above.
Quality of life
The trial team will ask you to fill out a questionnaire:
- before you start treatment
- people in group 2 and 4 fills 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 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:
- a physical examination
- blood tests
- CT scan
- bone marrow test
- heart trace (
ECG ) - heart scan (
ECHO )
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:
- a drop in blood cells causing an increased risk of infection, bruising and bleeding
- high blood pressure (hypertension)
- diarrhoea or constipation
- tiredness
- feeling or being sick
- cough
- swelling of your hands and feet
- skin rash
- high temperatures (fever)
- dizziness
- painful joints and muscles
- headache
- shortness of breath
- tummy (abdominal) pain
- loss of appetite
- indigestion
- sore mouth
- nerve damage causing weakness, tingling, numbness and pain in the hands and feet (peripheral neuropathy)
- skin infection
- sinus infection (sinusitis)
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.
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.
Chief Investigator
Professor Peter Hillmen
Supported by
Cancer Research UK
Abbvie
Janssen Pharmaceuticals
University of Leeds
Other information
This is Cancer Research UK trial number CRUK/12/037.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
