"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”
A trial looking at a new vaccine to treat acute myeloid leukaemia that has come back after a stem cell transplant (RFUSIN2-AML1)
This trial is looking at a new vaccine made by altering people’s own donated leukaemia cells and injecting them back to trigger their immune system. You have the vaccine with the standard treatment of having white blood cells through a drip into a vein.
More about this trial
If you have acute myeloid leukaemia (AML) that has come back after a stem cell transplant, you may have more chemotherapy, together with a drip containing white blood cells called leucocytes (donor leucocyte infusions or DLIs). The leucocytes help the body’s immune system to attack the leukaemia cells. But although this works well for some people, unfortunately it will not work for everyone.
This trial is also looking at using the body’s immune system response, but by creating and testing a personal vaccine for people with leukaemia. Scientists will put 2 genes called B7.1 and IL-2 into some of your leukaemia cells and grow them in the laboratory. These will be cells that were collected either when you were diagnosed, or when your leukaemia came back. When they have enough cells, they will treat them with radiation to stop them dividing. You then have these cells as injections under your skin. The added genes should stimulate your immune system to recognise and attack leukaemia cells.
Results from laboratory tests are encouraging. Now researchers need to see if this method is safe and works in people with leukaemia. The aims of this trial include
- Seeing how well the body copes with the AML cell vaccine and donated white blood cell infusions
- Learning more about possible side effects
- Looking at any response by the body’s immune system against the AML as a result of the vaccine and donated white blood cells
Who can enter
This trial is recruiting people who have had a transplant for AML. You can enter the trial either when your AML comes back or after you’ve had chemotherapy for AML that has come back.
You may be able to enter this trial if you
- Have AML that came back after you had a transplant with a lower dose of chemotherapy and donated stem cells (a reduced intensity conditioning donor stem cell transplant)
- Still have some leukaemia cells in your body after your transplant
- Had more CD3 markers from your donor than made by your own body when your AML came back – you can ask you doctor more about this
- Agree to the trial team collecting and storing your newly developing AML cells (AML blasts)
- Are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
- Are at least 18 years of age
You may be able to enter this trial if
- You have already had chemotherapy to treat AML that came back after transplant
- The chemotherapy reduced the number of developing AML cells (blasts) in your bone marrow to less than 5 in 100 (5%)
- You have satisfactory blood test results
- You are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
- You are willing to use reliable contraception throughout the trial if there is a chance that you or your partner could become pregnant
- You are at least 18 years of age
You will not be able to enter this trial if your AML has come back but you
- Are not well enough to have chemotherapy
- Have any other cancer apart from an early cancer called carcinoma in situ that has been successfully treated
- Have HIV
You will not be able to enter this trial if you have had chemotherapy to treat AML that came back but you
- Have a condition where the cells from your stem cell transplant are attacking your own cells (Graft versus Host Disease or GvHD)
- Are having other types of treatment for your AML
- Have any other cancer apart from an early cancer called carcinoma in situ
- Have a heart condition that is a cause for concern
- Are pregnant
- Have HIV, Hepatitis B or Hepatitis C
If you joined the trial because your AML came back after your transplant, but you have not yet had further chemotherapy, you will have this first. Then you may be able to take part in the trial if
- The chemotherapy has lowered the number of developing AML cells (blasts) in your bone marrow to less than 5 in 100 (5%)
- You are well enough
- You do not have any problems in the last list above
This phase 1 trial will recruit up to 12 people, into 2 groups.
If you are in group 1, you have at least 3 doses and up to 4 doses of white blood cells from your stem cell donor, 6 weeks apart. You have these blood cells through a drip into a vein. These are called donor leucocyte infusions (DLI). The dose of DLI will increase each time you have one.
If you are in group 2, you have at least 3 doses and up to 4 white blood cell infusions (DLI) in the same way as group 1. On the same days, you also have the AML cell vaccine, as an injection under the skin of your tummy (abdomen). If you do not have any side effects with your first vaccine, your next dose will be a little higher. And so on, until you have completed at least 3 treatments and up to 4 treatments. Doctors call this ‘dose escalation’.
The number of injections you have altogether will depend on the number of your leukaemia cells they were able to use to make your vaccine.
It is possible that the team may not need to use all of the cells and tissue they’ve collected from you during the procedures in this trial. They will ask if you would be willing for them to store any samples left over, to use in future research. You do not have to agree to this if you don’t want to. You can still take part in the trial.
Before you start the trial you will see the doctor and have some tests. These tests include
- Physical examination
- Blood tests
- Urine tests
- Heart trace (ECG)
- Chest X-ray and heart ultrasound (if needed)
- Bone marrow tests
- Taking a small sample of your skin (biopsy) – to look at any possible immune system reactions against cells other than your leukaemia cells
You see the doctor and have a blood test before and 3 weeks after every trial treatment you have. You also have a bone marrow test 10 weeks after starting treatment.
If you are having the AML cell vaccine, you stay in hospital for 24 hours after each dose, so the team can monitor you for side effects.
After you finish the trial treatment, the team will monitor you closely over the next 23 weeks (during 4 hospital visits), for side effects and signs that your immune system has reacted to the treatment. During this time you will have more
- Physical examinations
- Skin biopsies
- Chest X-ray and heart trace or heart ultrasound (if needed)
- Lung function test if (needed)
- Blood tests
- Bone marrow tests (2 altogether)
You finish seeing the trial team 45 weeks after you started your trial treatment.
Possible side effects of the leukaemia cell vaccine may include
- Itching, redness or swelling where you had your injection
- An increased risk of your body rejecting your stem cell transplant
- An increased risk of Graft versus Host Disease (GvHD), including symptoms such as rash, diarrhoea and liver problems
- A condition that causes fluid to leak out of small blood vessels into surrounding tissues (capillary leak syndrome), causing low blood pressure, low urine output, difficulty in breathing, weight gain and swelling in the ankles, legs and face (oedema) – the team will monitor you for 24 hours after having the vaccine
- Possible risks to unborn children – you must use approved contraception for the agreed time
If your AML comes back, or if your body does not cope well with the trial treatment for any reason, you will stop having it. But the team will continue to monitor you until the trial finishes, to make sure that your side effects get better, and to collect further information for the trial. Once you stop treatment you continue to see your AML specialist team in the same way as before the trial.
Scientists have tested the vaccine in this trial a lot in the laboratory. The genetically engineered virus that they use to carry the B7.1 and IL-2 genes into your stored leukaemia cells comes from the HIV virus. The scientists have made sure that the virus can get into leukaemia cells when they are making the vaccine. But once inside the cells, it cannot make more of itself and cause illness. Although it is extremely unlikely that any new virus may develop after you have these injections, the team will still monitor you closely.
They also treat the altered cells with radiation before they are made into your vaccine, so they will not divide after they have been injected.
Although the scientists have tested this vaccine a lot in the laboratory, there may be side effects from these treated cells that researchers don’t know about yet. This is one reason they are running this trial. Your trial team will monitor you closely, and you can speak to them if you have any concerns.
How to join a clinical trial
Dr Pramila Krishnamurthy
Experimental Cancer Medicine Centre (ECMC)
Guy's and St Thomas' NHS Foundation Trust
King's College London
Kings College Hospital NHS Foundation Trust
NIHR Biomedical Research Centres (BRCs) Award