GLOW: a phase 3 trial testing ibrutinib and venetoclax for people with untreated chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL)

This trial is comparing the combination of two targeted drugs, ibrutinib and venetoclax, with a standard first-line treatment of obinutuzumab and chlorambucil for people with CLL or SLL who are not able to have stronger treatments.

Purpose of trial

The aim of this trial is to find out if ibrutinib and venetoclax (I-VEN) can improve outcomes for people with CLL or SLL who are over 65 or who have other health conditions that mean they have limited treatment options. The trial is comparing this new regimen (combination of drugs), I-VEN, with a standard regimen of chlorambucil and obinutuzumab. This trial is looking at:

  • how effective each regimen is at putting CLL/SLL into remission (time without the condition getting worse)
  • how long remissions last with each regimen
  • the side effects of each regimen.


Ibrutinib is a cell signal blocker. It blocks signals that encourage cancer cells to grow. 

Venetoclax targets and blocks a Bcl-2, which is a protein important for the survival of some lymphoma cells. 

Obinutuzumab is an antibody treatment. It binds (sticks) to B cells (the white blood cells that are abnormal in CLL and SLL), allowing your immune system to get rid of the B cells.

Chlorambucil is a chemotherapy drug. 

All of these drugs are already used to treat people with CLL and SLL, but ibrutinib and venetoclax are not yet approved to be used together.

In this trial, participants are randomly assigned to one of two treatment groups:

  • ibrutinib and venetoclax (I-VEN)
  • obinutuzumab and chlorambucil (standard treatment).

You can’t choose which treatment you have and neither can your doctor. You are told which treatment you are having and you are given information about it.

If you are in the I-VEN group, you take both drugs orally (by mouth) as tablets or capsules. You take treatment every day for up to 18 months. Treatment is given in cycles of 28 days. 

  • For the first 3 cycles, you have ibrutinib alone.
  • You start venetoclax at a low dose at the beginning of cycle 4. The dose is increased gradually over the next 5 weeks. This helps to reduce the risk of serious side effects. 
  • You take venetoclax and ibrutinib together for 12 cycles.
  • You then take ibrutinib alone again for another 3 cycles (total of 18 cycles).

If you are in the standard treatment group, you have up to 6 cycles of treatment (each cycle is 28 days). You have obinutuzumab intravenously (into a vein) and you take chlorambucil as tablets.

  • In cycle 1, you have obinutuzumab once a week for 3 weeks and chlorambucil once every 2 weeks (twice per cycle).
  • In the next 5 cycles, you have obinutuzumab once every 4 weeks and chlorambucil once every 2 weeks. 

Who can enter

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

Approximately 200 people are needed for this trial.

You may be able to enter if:

  • You have CLL or SLL.
  • You are 65 or over or you are 18–64 and have health problems that make you unsuitable for other treatments.
  • You need treatment for your CLL or SLL.
  • Your CLL or SLL is measurable by the tests used in the trial.
  • You are well enough to take part in the trial.

You won’t be able to enter if:

  • You’ve already had any anti-cancer treatment for CLL or SLL.
  • You have certain genetic mutations (changes) in your CLL or SLL. These are called 17p deletions or TP53 mutations.
  • Your CLL or SLL has transformed (changed) into a faster-growing type of lymphoma. This is called ‘Richter’s transformation’.
  • You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment.
  • Your lymphoma is in your central nervous system (CNS; brain and spinal cord).
  • You have had major surgery in the last 4 weeks.
  • You have known bleeding problems (for example von Willebrand’s disease or haemophilia).
  • You are pregnant or breastfeeding.

Further information

More information about this trial is available at

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