A study looking at an intestinal microbiota transplant before a donor stem cell transplant for blood cancer (MAST)

Cancer type:

Acute leukaemia

Acute lymphoblastic leukaemia (ALL)

Acute myeloid leukaemia (AML)

Blood cancers

Chronic leukaemia

Chronic myeloid leukaemia (CML)

Myelodysplastic syndrome (MDS)

Status:

Open

Phase:

Phase 2

This study is looking at a type of treatment called intestinal microbiota transplant. It’s a way of encouraging more variety in gut bacteria.

It’s open to people having a bone marrow or stem cell transplant Open a glossary item with donor cells for:

acute myeloid leukaemia (AML)
acute lymphoid leukaemia (ALL)
acute leukaemia of ambiguous lineage
myelodysplastic syndrome (MDS)
chronic myelomonocytic leukaemia (CMML)
chronic myeloid leukaemia (CML)

More about this trial

Research has shown there are billions of ‘good’ bacteria and other microbes, such as viruses and fungi, living in our digestive system. This is also called the gut microbiome Open a glossary item .

We know that bacteria in the microbiome helps to:

digest our food
protect against other bacteria in the digestive system which can cause disease
control our immune system

People living with blood cancers often have antibiotics Open a glossary item a number of times due to their increased risk of infection. Antibiotics can reduce the number of ‘good’ bacteria in the digestive system leading to reduced variety in the microbiome.

You might have a bone marrow or stem cell transplant using donor cells for some types of blood cancer. It’s also called an allogeneic haematopoietic cell transplant (HCT).

HCT is a treatment to try and get rid of the cancer completely. It also weakens your immune system, so it doesn’t work as well. This means that you are more likely to get infections or find it difficult to get rid of them.

Researchers want to bring back the number and range of ‘good’ bacteria for people having these treatments. They think this might help to support your immune system to work better. They think a treatment called intestinal microbiota transplant (IMT) could help. But they aren’t sure. They are doing this study to try and find out.

For an IMT, scientists take bacteria from healthy people’s digestive systems. They do this by taking a sample of poo (stool). They process it in the laboratory to separate the bacteria and put it into capsules. You take the capsules by mouth. And the microbes are released into your digestive system.

The main aims of the study are to find out:

more about the benefits and side effects of an IMT
if an intestinal microbiota transplant can increase the range of ‘good’ microbes in people having a HCT using donor stem cells
how well the HCT works for people after an intestinal microbiota transplant when compared to a dummy drug (placebo )
about the quality of life of the people taking part

Who can enter

The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study 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 take part if you have one of the following:

acute lymphoblastic leukaemia, acute myeloid leukaemia or acute leukaemia which is not clearly lymphoid or myeloid called acute leukaemia of ambiguous lineage. And there is no sign of your cancer. This can be the first or second time your leukaemia has gone away completely.
advanced or high risk myelodysplastic syndrome (MDS)
intermediate or high risk chronic myelomonocytic leukaemia (CMML)
chronic myeloid leukaemia (CML) in the blast phase. Your CML must either be Philadelphia chromosome positive or have changes in the BCR-ABL gene .

Ask your doctor any questions you have around your risk group. They can explain what this means for you in terms of joining the study.

And if all of the following apply. You:

are well enough to have a bone marrow transplant or stem cell transplant (HCT) using stem cells from a donor (allogeneic transplant)
have had at least two cycles of intensive chemotherapy before joining the study
have had certain antibiotics which act against many types of bacteria in the 3 months before joining the study. These are called broad spectrum antibiotics, and your doctor will know which ones they are.
can mostly care for yourself but you may need help from time to time (Karnofsky performance status 60 or above)
are willing to use reliable contraception during treatment and for 6 months afterwards if there is any chance that you or your partner could become pregnant
are aged 18 or over

Who can’t take part

Cancer related
You cannot join this study if any of these apply. You:

have another type of cancer at the moment
have had another type of cancer in the past. You might be able to take part if you have had lobular carcinoma in situ (LCIS), have had basal cell or squamous cell skin cancer that has been fully removed, very early cervical cancer (in situ) that has been treated or early stage prostate cancer which is too small to be seen on a scan (this is T1a or T1b prostate cancer). You might be able to take part if you have had MDS, CMML or a myeloproliferative neoplasm (MPM) which has changed into AML. You might also be able to take part if you have had another cancer and had treatment to get rid of the cancer completely more than 5 years ago.
are not able to safely have a bone marrow or stem cell transplant. Your doctor can explain more.

Medical conditions
You cannot join this study if any of these apply. You:

have serious kidney or liver problems. Your doctor can explain more.
have an active infection, HIV, long term active hepatitis B or hepatitis C
have swallowing problems that mean taking capsules might be difficult
have digestive system problems such as food passing through the stomach more slowly than it should, coeliac disease , cystic fibrosis, inflammatory bowel disease, long term diarrhoea or either an abnormal hole or tunnel in the bowel
have an autoimmune disease and are having, or might need, treatment with steroids or any other medicine that affects the immune system
have a serious bleeding problem. You can still take part if you have had significant bleeding because of your blood cancer.
have low blood pressure needing a type of medicine called a vasopressor
have heart problems called valvular heart disease or you have changes to the structure of your heart

Other
You cannot join this study if any of these apply. You:

have had another microbiota transplant within the 3 months before joining the study
have taken probiotics after joining the study
have a very serious food allergy (anaphylaxis)
are allergic to anything the treatment capsule contains
are pregnant or breastfeeding

Trial design

This phase 2a study is taking place in the UK. The researchers need around 50 people to take part.

It is a randomised double blind study. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in. Nor will you or your doctor know which treatment you have. During the study your doctor will be able to find out what treatment you are having, if necessary.

There are 2 treatment groups. You have 1 of the following:

intestinal microbiota transplant
dummy drug (placebo)

19681-randomisation.png

Intestinal microbiota transplant
You have the intestinal microbiota transplant as capsules by mouth.

You take 10 capsules with water and will be given plenty of time to swallow them.

The picture below shows what the capsules look like:

19681-mast-diagram.png

Dummy drug (placebo)
You have 10 capsules which look like the intestinal microbiota transplant capsules. But they don’t have any medicine or microbes inside.

You take the 10 capsules with water and will be given plenty of time to swallow them.

Both groups
You have your capsules around 2 weeks before your stem cell infusion.

You have your HCT as part of your usual care. It’s not part of the study. Your HCT team will explain everything to you. This includes any possible side effects and how long you might stay in hospital. Ask them any questions you have.

Samples for research
You have tests for research before and after your HCT.

These are:

blood tests at the hospital
poo samples – you can bring a sample from home or do your sample in the hospital
urine tests – try and collect your first wee of the morning

The researchers use these samples to look at:

possible blood biomarkers
any changes in the microbes in your poo before and after the intestinal microbiota transplant
changes in substances in your wee related to the digestive microbiome before and after the intestinal microbiota transplant

Quality of life
The study team ask you to fill out some questionnaires:

before you have treatment
at set times during your HCT care
at set times during follow-up

The questionnaires ask about side effects and how you’ve been feeling. This is called a quality of life study.

After HCT
The study team look at your medical notes during the study to look at how you’re getting on after your HCT. This includes:

if you’ve had any fevers
if you’ve had any infections
any other side effects you’ve had from your HCT
what treatments you’ve been having
what has happened to your blood cancer after your HCT

Hospital visits

You see the doctor and have some tests before you can take part. These include:

a physical examination
blood tests
urine tests
poo sample – you can bring a poo sample the next time you come to hospital if you’re not able to collect a sample at this visit
pregnancy test – if there is any chance you could become pregnant

You go to the hospital around 2 weeks before your stem cell infusion.

You have:

either the intestinal microbiota transplant capsules or the dummy drug
blood tests

A week later you go back to the hospital to see the study team and have:

blood tests
poo tests
urine tests

Around a week later you have your HCT.

You see the study team and have blood, urine and poo tests on the day of your bone marrow or stem cell transplant. And then at certain points after your HCT. These are at:

1 week after your stem cell infusion
2 weeks after your stem cell infusion
3 weeks after your stem cell infusion

Follow up
The study team see how you are getting on after your HCT. This is at:

around 3 months after your stem cell infusion
around 7 months after your stem cell infusion
around a year after your stem cell infusion

Diary
You fill in a diary card each day about any side effects that you have. You do this for 2 weeks after the intestinal microbiota transplant. You go through it with the study team at your next visit. There’s a number to call in the diary if you are having problems filling it in.

Questionnaire about diet
At each visit you fill in a questionnaire about what you have been eating during the day of your tests. This is because some foods, such as fish and liquorice, can affect the results of your samples.

You don’t need to change your diet to take part in this study.

Side effects

The study 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.

There are some risks involved with having the microbiota transplant. But these are not common. They are: