A trial of venetoclax and azacitidine for acute myeloid leukaemia (VIALE M)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Acute leukaemia

Acute myeloid leukaemia (AML)

Blood cancers

Leukaemia

Status:

Closed

This trial is comparing venetoclax and azacitidine with azacitidine for acute myeloid leukaemia (AML). In this trial, the team are looking at having azacitidine as a tablet.

It is for people who have had chemotherapy and their leukaemia went away completely. This is called remission. It means there are no leukaemia cells in your blood or bone marrow. Open a glossary item

More about this trial

It is usual to have chemotherapy for acute myeloid leukaemia (AML). The aim of treatment is to get your leukaemia into remission Open a glossary item .

When you are in complete remission, you have regular tests and check ups with your doctor. You might also have blood transfusions or growth factors Open a glossary item to increase the number of blood cells in your bloodstream. This is called best supportive care.

There is a risk that your leukaemia will come back. So researchers are looking for new treatments to reduce this risk. In this trial they are looking at 2 drugs called venetoclax and azacitidine.

Venetoclax is a targeted drug Open a glossary item . It works by blocking a protein found in AML cells. This causes AML cells to die.

Azacitidine is a cancer drug that is already used for some people with AML.

In this trial, some people have venetoclax and azacitidine. And some have azacitidine and a dummy drug (placebo Open a glossary item ). You also have best supportive care if necessary.

The main aims of the trial are to:

confirm the dose of venetoclax to have with azacitidine
find out if venetoclax and azacitidine works better than azacitidine on its own
find the best dose of azacitidine that you have as a tablet with venetoclax
learn more about the side effects
find out more about quality of life

Who can enter

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.

Who can take part

You may be able to join this trial if all of the following apply. You:

had a new diagnosis of AML and are now in remission after having chemotherapy
have AML that went away completely within 4 months of joining this trial or it was no more than 75 days since your last chemotherapy
have a medium to high risk of the leukaemia coming back
are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
have satisfactory blood test results
are willing to use reliable contraception during treatment for a period of time after treatment if there is any chance you or your partner could become pregnant.
are at least 18 years old

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related
You:

have a type of leukaemia called acute promyelocytic leukaemia (APL)
have active leukaemia in the brain or spinal cord
are currently having treatment for AML
are suitable to have a stem cell transplant and the plan is for you to have one
have had any other cancer. This is apart from carcinoma insitu (CIS) of the cervix or breast, basal skin cancer , squamous cell skin cancer or any other cancer that was successfully treated and there have been no signs of it
have had treatment as part of a clinical trial in the last 30 days or the treatment hasn’t cleared your body yet

Medical conditions
You:

have a heart problem that is stable at rest but ordinary physical activity causes symptoms such as tiredness and shortness of breath
have a long term problem with your lungs and you need extra oxygen
have a problem with your digestive system that means you can’t absorb the trial medication
can’t swallow tablets
have a serious infection that needs treatment
have HIV unless it is stable and you are taking medication to treat it
have an active hepatitis B or hepatitis C infection
have taken any medication that blocks an enzyme called CYP3A4 in the 7 days before joining this trial
have any other medical condition or mental health problem that the trial team think would affect you taking part in the trial

Other
You:

have had an allergic reaction or you are sensitive to the trial treatments or anything they contain
have had a live vaccine within 4 weeks of joining the trial
are pregnant or breastfeeding or planning a pregnancy
have had grapefruit, Seville oranges or star fruit within 4 days of joining the trial

Trial design

This is an international phase 3 trial. The team need about 482 people to take part including about 20 to 30 people from the UK.

The trial is in 2 parts:

in part 1 the team want to confirm the best dose of venetoclax to have with azacitidine
in part 3 they are looking at the best dose of azacitidine to have as a tablet with venetoclax. They want to see if this improves treatment compared to standard treatment.

In both parts, you also have supportive care if necessary. This might include blood transfusions Open a glossary item or antibiotics to treat an infection.

The part you join depends on when you join the trial and the hospital where you are having treatment.

Part 1
About 20 people join part 1. Everyone in this part has venetoclax and azacitidine.

You have treatment in cycles Open a glossary item . Each cycle is 28 days. The first day of each treatment cycle is called day 1.

In part 1, you have azacitidine as an injection under the skin or as a drip into a vein. You:

have azacitidine on day 1 to 5
have no azacitidine on day 6 to 28

You have it only for the first 6 cycles of treatment.

Venetoclax is a tablet. You take them every day with a meal. The team let you know how many tablets to take. You have a diary to write down when you took them and how many.

You have treatment for about 2 years.

Part 3
In part 3, everyone has azacitidine and venetoclax. You have azacitidine as a tablet.

The first few people taking part have a low dose of azacitidine. The next few people have a higher dose if they don’t have any serious side effects. And so on, until they find the best dose. This is called a dose escalation study. The team need 36 people for the dose escalation study.

Once they find the best dose of azacitidine to have as a tablet they test this combination of treatment in a few more people.

The final part is randomised. 426 people join this part. A computer puts you into a treatment group. There are 2 groups. Neither you nor your doctor can decide which group you are in. You have one of the following:

azacitidine tablets and venetoclax
azacitidine tablets and a dummy drug (placebo)

You have treatment in cycles. Each cycle is 28 days. The first day of each treatment is called day 1.

You have:

azacitidine tablets on day 1 to 14
venetoclax tablets or the dummy drug. The trial team let you know how often you take them and how many to take.

You have treatment for about 2 years.

For all parts of the trial, you stop treatment if your leukaemia comes back. Your doctor will talk to you about other treatment options.

Samples for research
You give some bone marrow samples Open a glossary item and extra blood samples during treatment. You give these at specific times and the team will give you more information about this. They plan to use the samples to:

see how well treatment is working
find what happens to the drugs in the body (for people having venetoclax and azacitidine)
look for biomarkers to predict who will benefit from treatment
look at genes to help understand more about AML

You don’t have to agree to give the blood samples looking at genes if you don’t want to. You can still take part in the trial.

Quality of life
The trial team will ask you to fill out a questionnaire before you start treatment and at set times during treatment. The questionnaire asks about:

side effects
how you’ve been feeling

This is called a quality of life study. You complete the questionnaire on an electronic device.

Hospital visits

You see a doctor and have some tests before you join the trial. These include:

physical examination
blood tests
urine tests
heart trace (ECG )
bone marrow test

Everyone has a check up with the trial doctor once a month. You have regular blood tests during the trial.
You have a bone marrow test:

when you join the trial and at
3 months
6 months
9 months
12 months and then
every 3 months up until 24 months of treatment
when you stop treatment

When you stop treatment you see the trial doctor 1 month later.

Follow up if your leukaemia comes back
The team contact you every 3 months to see how you are getting on for up to 2 years. Or the team might see you at a routine clinic visit.

Follow up for people who had venetoclax and azacitidine and your leukaemia didn’t come back
You see the trial team every 3 months for a year if you stopped treatment but your leukaemia didn’t come back. And then you see them every 6 months until the end of the trial.

Follow up for people who had supportive care only and your leukaemia didn’t come back.
You see the trial team every 3 months for 1 year. And then you see them every 6 months until the end of the trial.

Virtual appointments and home visits
Due to the coronavirus pandemic some of the hospital visits are telephone or video appointments. And a nurse can visit you at your home or at another suitable location to make it easier for you to take part in this trial.

The nurse can:

check your blood pressure, temperature and heart rate
take blood samples
assess any side effects or changes in your health
check any changes in your medications

Side effects

The trial team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.

The most common side effects of venetoclax include: