A study looking at a new vaccine to treat leukaemia (WIN)

Who can enter

You can enter this study if you either

• Have chronic myeloid leukaemia (CML) that is stable and only developing slowly (chronic phase)
• Have tested positive for the Philadelphia chromosome
• Have been taking imatinib on its own for at least 2 years and are still taking it
• Have had blood or bone marrow tests which now show no signs of the Philadelphia chromosome (a cytogenetic response), but doctors can still find signs of CML cells in your blood

OR

• Have acute myeloid leukaemia that is ‘Wilm’s tumour 1’ positive, and tests show that you are in either ‘complete response’ or ‘morphologic response’ – you can check this with your doctor

AND you

• Are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
• Have satisfactory blood tests
• Have veins that the study team can take blood from easily
• Are willing to use reliable contraception during the study and for 6 months afterwards if there is any chance you or your partner could become pregnant
• Are at least 18 years old

You cannot enter this study if any of the following applies to you

People who have CML

• Your CML is in accelerated phase or blast crisis, or you have had a ‘complete molecular response’ during your imatinib treatment
• Doctors have changed your dose of imatinib in the last year, or you have stopped imatinib for more than 15 days in the last 6 months
• You have had treatment with interferon
• Your bone marrow has less than the normal number of cells – you can check this with your doctor

People who have AML

• Your AML has come back or you are suitable to have a donor stem cell transplant
• Your bone marrow has fewer than the normal number of cells (you have hypocellular bone marrow) – you can check this with your doctor
• Your doctor has told you that your AML is likely to do well (‘good risk’ AML)

Both

• You need to take steroid tablets or drugs that dampen your immune system - please note, you must never stop taking steroids without talking to your doctor first
• You have had major surgery in the last 4 weeks and have not yet recovered
• You have an uncontrolled infection
• You have a heart condition which is a cause for concern
• You have another medical condition that would make you unwell, or affect the results of the study
• Have had any other cancer, apart from non melanoma skin cancer that was successfully treated at least 5 years ago
• You have hepatitis B or C, HIV or a sexually transmitted infection called syphilis

Trial design

This study will recruit about 184 people into 2 groups. 92 people will have CML and 92 will have AML.

At the start of the study, everyone will have a blood test to look for a gene called Human Leucocyte Antigen (HLA A2). You need this gene for your immune system to be able to work with the vaccine. Being HLA A2 positive or negative will not affect the treatment of your condition, and it has no known effect on whether your cancer will get better or worse over time.

If you test positive for HLA A2, you will be in group 1 and have the vaccine. If you are HLA A2 negative, you will be in group 2. This is the control group, and you will not have the vaccine.

If you are in group 1, you will have a course of study vaccinations. You have 2 DNA vaccines once a month, for 6 months. You have the vaccines as an injection into a muscle in your arm or leg. At the same time as the injection, the nurse or doctor will pass a small electric current (lasting about half a second) through the needle. This is called electroporation, and it makes the vaccine work better by helping it enter the cells. The electric current may make your muscle jerk, a little like it would if you touched an electric fence.

You may feel a little pain and discomfort for a few minutes, and aches for a few days. The study team can offer you painkillers to help. If you are one of the first few people to have the vaccine in this study, you will stay at the hospital for a couple of hours so the team can watch for any side effects. You will also have a heart trace (ECG).

You will fill out a questionnaire straight after your injection, and 2 days later. This will ask you what you think about electroporation, compared with normal injections. If for any reason you cannot cope with the injections or electroporation, you can tell the team, and you will stop the study treatment. But if possible, the team would like you to carry on having the study blood tests so they can see how you are getting on.

Depending on how your immune system responds to the vaccine, you may be able to have more doses at regular intervals, until you have had them for 2 years.

Before, and 6 months after your first vaccination, the team would like to collect a larger amount of white blood cells. This is called leukapheresis. To collect these cells you will have a tube coming out of a vein in one of your arms. Your blood will pass through this tube, into a machine called a cell separator. This spins the blood to separate out the white blood cells that the doctors need. The remaining blood goes back into your body through a tube in your other arm. This takes up to 3 hours. You may have tingling in your tongue or fingers, or feel faint. But this only lasts a few minutes, and does not affect everyone.

At 3 and 6 months the team would also like to give you a small injection under the skin of pieces of WT1 (peptides). This is to work out if your immune cells can now find the WT1 pieces. If you have a skin reaction, the team would like to numb the area and take a small sample of skin (a biopsy) to look for immune cells that have reacted to WT1.

If you are in group 2 (the control group) you will not have the vaccine, but you will see the study doctor regularly and have some blood tests.

The team would also like everyone’s permission to store blood samples to look at in the future. You do not have to agree to this if you don’t want to.

If you have CML, you continue your imatinib treatment throughout the study, along with whatever other care your doctor thinks you need. If you have AML, and need further standard treatment, you can have this whether or not you are having the vaccines.

After the study, you continue to see your regular specialist in the same way as you did before.

Hospital visits

Before you start treatment you will see the doctor and have some tests. These tests include

• HLA status and a test to look for WT1 in your leukaemia cells
• Physical examination
• Heart trace (ECG) and heart ultrasound (echocardiogram) (group 1)
• Blood tests
• Chest X-ray (and in 6 months) (group 1)
• Bone marrow test
• Collecting white blood cells (leukapheresis) (group 1)

If you are in group 1, you will have the vaccine every month for 6 months, then 6 more times over the next 18 months.

You will also visit the hospital for tests 12 times in the first 34 weeks. Then, between 11 and 36 months after starting the study you visit the hospital approximately every 3 months.

At each of these visits you will have

• Physical examination
• Blood tests
• Urine tests

Before each vaccination you will have a blood test. After each vaccination you will have a

• Heart trace (ECG)
• Questionnaire to check for pain or discomfort at the injection sites

Between weeks 24 and 28 you will have a

• Bone marrow test
• White blood cell collection (leukapheresis)
• Check for hypersensitivity (and at week 12)

If you are in group 2, once you have joined the study you will visit the hospital the same number of times as group 1, but you will simply see the doctor and have some blood tests.

Side effects

DNA vaccination is a new treatment, which has only been tested in small groups of people so far. All the information the researchers have suggest that DNA vaccines are safe. But a DNA vaccine with WT1 has not been tested in people before.

In vaccinations with short pieces of the WT1 protein (peptides), side effects have included

• A drop in white blood cells (in people with myelodysplasia) - people with good numbers of bone marrow cells did not have a drop in their blood cell numbers
• Possible changes to kidney function

You may also have pain and discomfort where you had your injection.