BGB-3111-304: a randomised phase 3 trial comparing zanubrutinib with a standard treatment for people with untreated chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL)

This trial is testing whether a new targeted drug, zanubrutinib (also called BGB-3111), could improve outcomes compared with a standard chemo-immunotherapy treatment (chemotherapy with antibody therapy) for people with CLL or SLL who have not yet received treatment.

People who are not fit enough to have FCR chemo-immunotherapy might be able to enter this trial. 


Purpose of trial

The aim of this trial is to compare the safety and effectiveness of:

  • Zanubrutinib given alone
  • bendamustine with rituximab (a standard first treatment for CLL or SLL).

Treatments

Zanubrutinib is a cell signal blocker that works by interfering with B cell signalling (the type of white blood cell that is abnormal in CLL and SLL). Interfering with the cells’ signals can prevent them from dividing or make them die.

Bendamustine is a chemotherapy drug. Rituximab is an antibody treatment. The combination of these two drugs is already used to treat people with CLL and SLL. 

In this trial, you have one of the following two treatments: 

  • Zanubrutinib alone
  • bendamustine and rituximab.

If your CLL or SLL cells do not have a genetic change called ‘17p deletion’, you are randomised (randomly assigned a group by computer) to have one of the two treatments. You can’t choose which treatment you have, but you are told which treatment you are having and given information about it.

If your CLL or SLL cells have a 17p deletion, this means you are less likely to respond to chemoimmunotherapy. Everyone with a 17p deletion has zanubrutinib alone. 

If you are having zanubrutinib, you take it orally (by mouth) as capsules twice a day. You can continue this treatment as long as your doctor thinks that it is benefitting you.  

If you are having bendamustine and rituximab, you have both drugs intravenously (into a vein). You have it in cycles, where a cycle is 4 weeks (28 days) long.

  • You have bendamustine on the first 2 days of each cycle.
  • You have rituximab the day before you start treatment with bendamustine in the first cycle, then on the first day of each following cycle.

You can have up to 6 cycles of bendamustine and rituximab.


Who can enter

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

Approximately 467 people are needed for this trial.

You may be able to enter if:

  • You have CLL or SLL and your cancer cells have CD20 (the target for rituximab).
  • You have not yet had treatment for your CLL or SLL, but you need to start treatment.
  • You are not fit enough to have a different first-line treatment, called FCR. 
  • You are well enough to take part in the trial.
  • Your blood and other health test results are satisfactory.
  • You and your partner are willing to use effective contraception during the trial if there is any chance of you or your partner becoming pregnant.
  • You are 18 or over.

You won’t be able to enter if:

  • You’ve already had treatment for your CLL/SLL.
  • You have prolymphocytic leukaemia.
  • Your CLL/SLL has transformed (changed) into a faster-growing type of lymphoma. This is sometimes called ‘Richter’s transformation’.
  • You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment, for example heart problems, lung problems, an infection or problems with severe bleeding.
  • You’ve had another cancer in the last 3 years, unless it was certain localised cancers.
  • You’ve had major surgery or injury in the last 4 weeks.
  • You’ve had a stroke or bleeding on your brain in the last 6 months.
  • Your CLL/SLL is in your central nervous system (CNS; brain and spinal cord).
  • You have HIV or active hepatitis B or hepatitis C.
  • You can’t swallow capsules or you have digestive problems that might make it difficult for you to absorb the treatment.
  • You are taking certain medications that affect cytochrome P450 subtype CYP3A (enzymes in your body) – your doctor can advise if this applies to you.
  • You’ve had a live vaccine in the last 35 days.
  • You have had a bad reaction to one of the trial drugs or their ingredients in the past.
  • You are taking part in another clinical trial that involves treatment.
  • You are pregnant or breastfeeding.

Further information

More information about this trial is available at www.clinicaltrials.gov/ct2/show/study/NCT03336333

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