A study of venetoclax and ibrutinib for chronic lymphocytic leukaemia (CLARITY)

Cancer type:

Blood cancers

Chronic leukaemia

Chronic lymphocytic leukaemia (CLL)

Leukaemia

Status:

Results

Phase:

Phase 2

This study was for people with chronic lymphocytic leukaemia (CLL) that had come back after treatment, or treatment had stopped working.

It was open for people to join between 2016 and 2017, and the team published the results in 2019.

More about this trial

Doctors often use chemotherapy or targeted drugs to treat chronic lymphocytic leukaemia (CLL).

Ibrutinib is a type of targeted treatment called a cancer growth blocker. It stops signals that cancer cells use to divide and grow.

Venetoclax is also a type of targeted treatment. It stops a protein found in CLL cells working and this causes the cells to die.

When this trial was done, patients usually had one treatment at a time. And they often had treatment for a long time, until there were signs that their CLL had started to grow again.

Doctors in this trial wanted to find out whether they could do a test to see if the treatment had worked and the leukaemia had gone. And then stop treatment if it had.

To do this, they measured the number of leukaemia cells in blood and bone marrow samples. This is known as measurable residual disease (sometimes called minimal residual disease), or MRD.

People with fewer than 1 leukaemia cell per 10,000 white blood cells are classed as MRD negative and being in remission. Research has shown that people who are MRD negative after treatment are more likely to live longer than those who remain MRD positive.

Researchers hoped that the combination of ibrutinib and venetoclax might be a useful treatment for CLL that had come back after treatment. And that it would help reduce the level of MRD people had.

The main aims of the trial were to find out:

whether ibrutinib and venetoclax could reduce the amount of measurable residual disease people had
more about the side effects

Summary of results

The results showed that ibrutinib and venetoclax could be a useful treatment for CLL. And that it didn’t cause too many side effects.

Trial design
This trial was for people with chronic lymphocytic leukaemia (CLL). They had all had at least one course of treatment before, but their CLL had come back or continued to get worse.

This was a phase 2 trial and everyone taking part had the same treatment. The plan was for people to start with having ibrutinib for 2 months. And then have and both ibrutinib and venetoclax after that.

Results
A total of 54 people took part in this trial:

4 people had ibrutinib but stopped treatment before having venetoclax
50 people had ibrutinib followed by both ibrutinib and venetoclax

The research team were able to look at how well treatment had worked in 53 of the people who took part. They did this 14 months after people started treatment, so after 12 months of having both treatments.

They found that the leukaemia had responded to treatment in 47 people (89%). It had:

gone away in 27 people (51%) – they were in remission
got a bit better in 20 people (38%)

Bar Chart 1

They also looked at how many people had measurable residual disease (MRD) in blood and bone marrow samples.

They found that:

28 people (53%) had blood test which was MRD negative
19 people (36%) had a bone marrow test which was MRD negative

Bar Chart 2

This was higher than they were expecting.

Two people who were MRD negative and in remission decided to stop treatment at this point. When the researchers analysed the results in November 2018, these 2 people were both still in remission.

The other people taking part in the trial decided to continue with treatment. Everyone who took part was living at time of analysis in 2018.

Side effects
Some people taking part had side effects. But most were mild or didn’t last long. The most common side effect was a drop in white blood cells.

One person had a temporary increase in potassium and creatinine in their blood. This was caused by the breakdown of leukaemia cells and is called tumour lysis syndrome.

Conclusion
The research team concluded that the combination of ibrutinib and venetoclax could be a useful treatment for people who have already had treatment for CLL. And that it didn’t cause too many side effects.

They think it may be possible to give treatment until people are MRD negative and then stop. Rather than give treatment continuously.

The team suggest larger phase 3 trials are done to find out more about how well this treatment combination works longer term.

Where this information comes from
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.