Acalabrutinib in CLL: a phase 3 trial comparing acalabrutinib with other treatments for people with relapsed or refractory chronic lymphocytic leukaemia (CLL)

This trial is comparing acalabrutinib with other treatments for people with chronic lymphocytic leukaemia (CLL) that has relapsed (come back) or was refractory (didn’t respond) to previous treatment.


Purpose of trial

The trial is comparing:

  • the safety of the different treatments
  • how well each treatment works.

Treatments

Acalabrutinib and idelalisib are cell signal blockers. They work in different ways to block signals that encourage CLL cells to grow. Idelalisib is already approved to treat some people with CLL.

Rituximab is an antibody treatment widely used to treat CLL and other types of lymphoma.

Bendamustine is a chemotherapy drug.

Participants are randomised to 1 of 2 groups:

  • group 1 have acalabrutinib on its own
  • group 2 have standard treatment of rituximab with either idelalisib or bendamustine.

If you are in group 1, you take acalabrutinib orally (by mouth) twice a day every day for as long as the treatment is helping you. You can take the capsules at home.

If you are in group 2, your doctor can decide whether idelalisib or bendamustine would be best for you.

In group 2:

  • Idelalisib and rituximab group: you have rituximab intravenously (through a drip into a vein) on day 1 of each cycle for up to 8 cycles. You also take idelalisib orally twice a day and continue to take it for as long as it is helping you.
  • Bendamustine and rituximab group: you have rituximab intravenously on day 1 of each cycle and bendamustine intravenously on day 1 and 2 of each cycle. You have up to 6 cycles of treatment.

Each cycle of treatment is 4 weeks.


Who can enter

Your consultant can give you advice on whether this trial might be suitable for you.

Around 306 people are needed for this trial.

You may be able to enter if:

  • You have CLL and your CLL cells have a protein called ‘CD20’, which is the target for rituximab.
  • You have had one or more previous courses of treatment for CLL.
  • Your CLL needs treatment.
  • You are well enough to look after yourself and are up and about at least 50% of the day even if you are unable to work.
  • Your blood and other health test results are satisfactory.
  • You are 18 or over.

You will not be able to enter if:

  • You have prolymphocytic leukaemia.
  • Your lymphoma is in your central nervous system (CNS; brain and spinal cord).
  • Your CLL has transformed (changed). This might be called ‘Richter’s syndrome’ .
  • You have had a BCl-2 inhibitor drug (fpr example venetoclax ) or a B-cell receptor inhibitor drug (for example idelalisib or ibrutinib) before.
  • You have had certain antibody treatments where an antibody is joined to a radioactive drug or a toxin (poison).
  • You have certain conditions that are not under control, including autoimmune haemolytic anaemia or idiopathic thrombocytopenic purpura.
  • You have had other anti-cancer treatments in the last 30 days, including chemotherapy, radiotherapy, antibody treatment or experimental treatments.
  • You have had major surgery in the last 30 days.
  • You have had another cancer in the last 2 years except certain localised cancers.
  • You have significant heart problems.
  • You have HIV, cytomegalovirus (CMV), hepatitis B, hepatitis C or an uncontrolled infection that affects your whole body.
  • You have or have had pneumonitis (lung inflammation) that was caused by medication.
  • You have a condition that could prevent the trial drugs being properly absorbed by your body.
  • You have had a live vaccine in the last 28 days. Your doctor can advise if this applies to you.
  • You have had a stroke or bleeding in your brain in the last 6 months.
  • You have ever had problems with bleeding.
  • You have taken blood-thinning medication (eg warfarin) in the last 7 days.
  • You are taking a medication that could interfere with the study treatment by affecting an enzyme in your body called ‘CYP3A’. Your doctor can advise if this applies to you.

Further information

More information about this trial is available at clinicaltrials.gov.