A trial looking at a type of gene therapy for acute myeloid leukaemia and myelodysplastic syndrome

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
Myelodysplastic syndrome (MDS)

Status:

Closed

Phase:

Phase 1/2

This trial is looking at a new treatment that changes certain immune system cells called T cells, so they can recognise diseased blood cells.

It is for people who have one of the following conditions and it didn’t get better after having a drug called azacitidine

More about this trial

Doctors can treat acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) with a drug called azacitidine. But researchers are looking for new treatments that people can have if their AML or MDS doesn’t respond to azacitidine as well as their doctors had hoped. In this trial, they are looking at an experimental treatment which uses cells in your immune system called T cells.

The trial team will take some of the T cells from your blood and change (modify) them in the laboratory. They grow the T cells together with a modified virus. The virus contains a gene Open a glossary itemwhich has been changed so that it recognises a protein called WT1.

The WT1 protein is important because it is found in high levels on diseased blood cells, but only at very low levels elsewhere in the body. It is usually invisible to normal T cells. But the modified T cells should be able to recognise the WT1 protein and attack the diseased cells.

This is a type of gene therapy. The technical name for the treatment is gene modified WT1 T cell receptor (TCR) therapy.

The aims of the trial are to

  • Learn more about this new treatment and how well it works
  • See whether it is safe

Who can enter

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

  • You have acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) that is classed as intermediate or high risk (your doctor can advise you about this)
  • Less than 30% of the cells in your bone marrow Open a glossary item and less than 10% of the cells in your bloodstream are immature cells called blasts
  • You have a low number of at least 1 type of blood cell Open a glossary item (your doctor can advise you about this)
  • You finished having azacitidine at least 4 weeks ago, but no longer than 2 months ago
  • If the number of blasts in your bone marrow increased after you had azacitidine, the amount after treatment must be less than double the amount there were before you had azacitidine
  • You have a substance in your blood called HLA-A*02 (the trial doctors will test a sample of your blood for this)
  • You are willing to have a procedure called leukapheresis to collect white blood cells from your blood
  • You are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
  • You are at least 18 years old
  • You are willing to use reliable contraception during the trial and for at least 6 months afterwards if there is any chance you or your partner could become pregnant

You cannot join this trial if any of these apply.

  • You have a type MDS called chronic myelomonocytic leukaemia (CMML) and you have a high number of white blood cells (the trial doctor can advise you about this)
  • You have a type of AML called acute promyelocytic leukaemia (M3)
  • You have a very low number of white blood cells called lymphocytes Open a glossary item (your doctor can advise you about this)
  • You could have a stem cell transplant using cells from a donor
  • You need to take steroids Open a glossary item and would not be able to stop taking them for at least 2 weeks during the trial (it is important that you don’t stop taking any medication before discussing it with your doctor)
  • You need to have chemotherapy Open a glossary item straight away or are already having a drug such as decitabine
  • You have had treatment with T cells that have been changed in a laboratory (gene modified T cell therapy)
  • You have had treatment as part of another clinical trial in the last 4 weeks
  • You have had radiotherapy Open a glossary item in the last 2 weeks
  • You have had surgery in the last 4 weeks and haven’t fully recovered yet
  • You currently have any other type of cancer apart from a very early stage cancer (carcinoma in situ Open a glossary item) of the breast or cervix, or non melanoma skin cancer
  • You still have side effects from earlier chemotherapy (apart from effects on your blood) unless they are very mild
  • You have certain heart or lung problems, or high blood pressure that can’t be controlled with medication
  • You have an autoimmune disease Open a glossary item such as rheumatoid arthritis or multiple sclerosis
  • You have HIV, hepatitis B or C, syphilis or a virus called  HTLV-1
  • You have problems with your liver or kidneys, or need to have dialysis
  • You have an infection, another medical condition or a mental health problem that the trial team think could affect your taking part
  • You are known to be very sensitive to the chemotherapy drugs cyclophosphamide or fludarabine, the steroid drug methylprednisolone, or a drug called interleukin 2 (IL2)
  • You are pregnant or breastfeeding

Trial design

This is a phase 1/2 trial. The researchers need about 25 people to join. Everybody taking part will have the experimental treatment.

Firstly the trial team need to remove some T cells from your blood. To do this, they put a small tube into one of your veins (usually in your arm). Blood passes down the tube and through a machine called a cell separator which removes the cells needed. The rest of your blood is then returned to you via a tube into another vein (usually in your other arm). This usually takes 4 to 5 hours.

The researchers will use gene therapy to change (modify) these cells in the laboratory and make them better at finding and attacking diseased blood cells.

Within a few weeks, you go back to hospital and have chemotherapy Open a glossary item. You have drugs called fludarabine or methylprednisolone. You have both drugs for 5 days.

The reason you have these chemotherapy drugs is to temporarily reduce the number of your own T cells. This will create space for the modified T cells and should help them to survive for longer in your body.

You then have 2 days without any treatment before having the modified T cells through a drip into a vein. This takes between 30 minutes and an hour.

After having the T cells, you have a drug called interleukin 2 (IL2) as an injection under your skin once a day for 5 days.

You have IL2 because it activates cells in your immune system and the researchers think this will help the modified T cells to live longer and work better. The trial team will teach you how to give yourself the injections at home.

If your leukaemia (or MDS) doesn’t respond to the treatment, your doctor may suggest you have modified T cells a 2nd time.

Hospital visits

You see the trial team and have a number of tests before you start treatment. The tests include

  • Physical examination
  • Blood tests
  • Urine tests
  • Heart trace (ECG) Open a glossary item
  • Bone marrow test Open a glossary item

You have most of the trial treatment as an outpatient. But after having the modified T cells, you may need to stay in hospital overnight. You then go back to hospital 3 days and 7 days later to see the trial doctor and have more blood tests. After that, you have appointments

  • Once a week for 6 weeks
  • Then once a month until 6 months after treatment
  • Then every 2 months until at least a year after treatment

At some of these appointments you may need to have a bone marrow test and more blood tests.

If you have modified T cells a 2nd time, you will need to go to hospital to repeat all the tests and visits you had the 1st time.

Side effects

As gene modified WT1 TCR therapy is a new treatment, there may be side effects we don’t know about yet. The side effects of similar experimental treatments have included

  • Mild flu like symptoms such as high temperature (fever) and aching
  • Feeling or being sick

Less common, but more serious side effects have included

  • Difficulty breathing
  • Low blood pressure
  • Kidney failure
  • Blood clotting problems

The trial team will talk to you about all the possible side effects before you agree to take part. During the trial, they will monitor you very closely and at each hospital visit, they will ask about any side effects you’ve had.

If you do have any new symptoms, or problems that are getting worse, you should tell the trial team straight away. They will give you a phone number to contact them between hospital visits

Common side effects of fludarabine include

Common side effects of methylprednisolone include

  • A temporary increase in your blood sugar
  • Problems sleeping (typically, this lasts a couple of days)

Interleukin 2 can cause soreness or redness around the site of the injection.

We have more information about

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr. Emma Morris

Supported by

Cell Therapy Catapult
Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

12641

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Wendy took part in a new trial studying the possible side effect of hearing loss

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"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”

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