Purpose of trial
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.
Note: This trial was initially comparing ibrutinib and rituximab with FCR but two more treatment groups were added in July 2017: ibrutinib alone and ibrutinib and venetoclax. The researchers want to find out:
- which drug combination of the two works better as a first treatment for CLL
- more about the side effects of ibrutinib and the new treatment combinations
- whether ibrutinib or the new treatment combinations affect 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
Your consultant can give you advice on whether this trial might be suitable for you.
1516 people are needed for this trial.
You may be able to enter if:
- You have B-CLL or small lymphocytic lymphoma.
- Your CLL stage is B or C, or is stage A but is getting worse (progressive stage A).
- Your specialist thinks your CLL needs to be treated.
- You have at least one of the following:
- Anaemia or low platelet count that is getting worse
- CLL causing enlargement of your spleen or lymph nodes, which is getting worse or causing symptoms
- White cell count that is rapidly increasing
- Lost a tenth or more of your weight in 6 months without meaning to
- Tiredness that prevents you from working or carrying out your normal routine
- Temperature over 38.0oC for 2 weeks or more without an infection
- Night sweats for more than a month without an infection.
- You are well enough to have chemotherapy.
- You are well enough to look after yourself and are up and about more than 50% of your waking hours, even if you are not well enough to work.
- You and your partner are willing to use reliable contraception if there is any chance of you or your partner becoming pregnant.
- Your blood and other health test results are satisfactory.
- You are between 18 and 75.
You will not be able to enter if:
- You have already had treatment for CLL.
- Your CLL has transformed into Richter’s syndrome.
- More than 1 in 5 of your CLL cells have lost a working copy of a gene called P53.
- You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment.
- You can’t swallow tablets or capsules.
- Your CLL is in your central nervous system (CNS; brain and spinal cord).
- You’ve had major surgery in the last 4 weeks.
- You are taking warfarin or any other anti-clotting drugs.
- You are taking certain other drugs that might interfere with the study treatment.
- You have HIV, hepatitis C or hepatitis B.
- You have any type of infection.
- You have had another cancer in the last 3 years, except certain localised cancers.
- You are pregnant or breastfeeding.
- You have very low blood counts that are not caused by CLL.
- You’ve had a severe allergic reaction to antibody treatment in the past.
- You have had a stroke in the last 6 months.
- You take other medication that prevents an enzyme in your body called CYP from working properly.
- You have serious problems with your heart, breathing or digestive system.
More information about this trial is available at Cancer Research UK.