Purpose of trial
This is a phase 1 (early phase) trial of an experimental treatment. Little is known about the safety and effectiveness of this treatment. You might not benefit from the treatment but the trial will give important information about this new treatment, which could help other people in the future.
The aim of this trial is to find out more about using a new treatment called tirabrutinib to treat B-cell lymphomas. The trial is for people whose lymphoma has relapsed (come back) or is refractory (has not responded to treatment).
The trial aims to find out:
- the best dose to use
- the side effects
- how well the treatment works
- how the treatment behaves in the body.
Tirabrutinib is a targeted drug that works by blocking the action of a protein called bruton agammaglobulinemia tyrosine kinase (BTK). The BTK protein is part of a signalling pathway that controls how B cells grow and divide. Blocking this protein in lymphoma cells with tirabrutinib could cause them to die or control their growth. Tirabrutinib is also known as ONO/GS-4059.
Tirabrutinib is a tablet or capsule that you take either once or twice a day, depending on the dose you are having. Everyone in this trial takes tirabrutinib every day. Different doses of tirabruitnib are being tested in this trial.
The trial is in two parts.
- Part 1 is to find out the highest safe dose of tirabutinib alone or with other treatments This is done by ‘dose escalation’. Participants are treated in groups of three. The first three participants have the lowest dose of tirabrutinib. The next three have a higher dose. This continues and the participants are monitored closely for side effects. The highest dose that doesn’t cause serious side effects is used in part 2 of the trial.
- Part 2 is to test how well the highest safe dose of tirabrutinib works. People entering this part of the trial all have the same dose of tirabrutinib.
You may also have other lymphoma drugs as part of this trial. The combinations being tested are:
- tirabrutinib with another lymphoma drug called idelalisib, which is a tablet you take twice a day
- tirabrutinib with another lymphoma drug called entospletinib, which is a tablet you take twice a day
- tirabrutinib with idelalisib and another lymphoma drug called obinutuzumab, which you have intravenously (as an injection into a vein)
- tirabrutinib with entospletinib and obinutuzumab.
If you have chronic lymphocytic leukaemia (CLL), you may have tirabrutinib alone, either once or twice a day.
Whichever group you are in, you can continue to have the trial treatment for up to 2 years. Your doctor should give you more information about the treatment you are having.
Who can enter
Your consultant can give you advice on whether this trial might be suitable for you.
Around 368 people are needed for this trial.
You may be able to enter if:
- You have follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, chronic lymphocytic leukaemia, mantle cell lymphoma, Waldenstrom’s macroglobulinaemia, or diffuse large B-cell lymphoma (non-germinal centre B-cell type) that has come back or not responded to treatment.
- You have previously had at least 2 courses of treatment for your lymphoma (or at least 1 if you have CLL).
- Your lymphoma is measurable by the tests used in the trial (apart from Waldenstrom’s macroglobulinaemia).
- 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 are willing to take medications to help prevent a lung infection called pneumocystis during the trial.
- 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 18 or over.
You will not be able to enter if:
- You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment.
- You are able to have a stem cell transplant to treat your lymphoma.
- You still have significant side effects from your previous treatment.
- You have been treated with a similar drug before.
- You can’t swallow tablets or capsules.
- You’ve had surgery in the last 4 weeks.
- You have had another cancer.
- You are taking or have taken certain other drugs.
- You have HIV, hepatitis C virus or hepatitis B virus.
- You have had another cancer in the last 5 years, except certain localised cancers.
- You are pregnant.
- Any of the study drugs are not suitable for you.
More information about this trial is available at clinicaltrials.gov.