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

Cancer type:

Acute leukaemia
Acute myeloid leukaemia (AML)
Blood cancers
Chronic leukaemia
Chronic myeloid leukaemia (CML)
Leukaemia

Status:

Open

Phase:

Phase 1/2

This trial is looking at a new treatment that changes immune system cells called T cells, so they can recognise leukaemia cells. The trial is for people who have one of the following

More about this trial

Doctors can treat leukaemia with chemotherapy Open a glossary item. You may also have a stem cell transplant. But researchers are always looking for new treatments. In this trial, they are looking at a type of gene therapy that 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 item that has been changed so it recognises a protein called WT1 which is usually invisible to normal T cells.

The WT1 protein is important because it is found in high levels on leukaemia cells. The modified T cells should be able to recognise the WT1 protein and attack the leukaemia cells. This treatment is called WT1 TCR gene therapy.

The aims of the trial are to

  • Find a safe dose of modified T cells to give
  • Learn more about the side effects
  • See if the gene modified T cells can recognise leukaemia cells
  • Look for signs that this works as a treatment for AML and CML

Who can enter

You may be able to join this trial if you are in one of the following situations.

As well as the above, all of the following must apply. You

  • Have a substance in your blood called HLA-A*02 (the trial doctors will test for this)
  • Finished chemotherapy at least 4 weeks ago
  • 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 between 18 and 75 years old
  • Are willing to use reliable contraception during the trial and for 6 months afterwards if there is any chance that you or your partner could become pregnant

You cannot join this trial if any of these apply. You

  • Have a very low number of white blood cells called lymphocytes Open a glossary item (your doctor can advise you about this)
  • Have had a chemotherapy drug called fludarabine in the last 3 months
  • Have had major surgery to your chest or tummy (abdomen) in the last 4 weeks and haven’t fully recovered yet
  • Are taking steroids Open a glossary item
  • Have certain heart problems (the trial team can advise you about this)
  • Have an infection that can’t be controlled, or another medical condition that the trial team think could affect your taking part
  • Have HIV, hepatitis B or C, syphilis or a virus called HTLV-1
  • Have had a bad allergic reaction in the past
  • Are pregnant or breastfeeding

Trial design

This is a phase 1/2 trial. The researchers need about 18 people to join. Everybody taking part will have WT1 TCR gene therapy.

The researchers are testing 2 different doses of T cells. The first few people taking part in the trial have a low dose of modified T cells. As long as they don’t have bad side effects, the next few people will have a higher dose.

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 leukaemia cells.

Within a few weeks, you go back to hospital and have a chemotherapy drug called fludarabine. You have this through a drip into a vein once a day for 5 days. It takes about half an hour each time. On the first day, you also have a drug called methylprednisolone through a drip into a vein. This takes another half an hour.

The reason you have these 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.

If the researchers find the T cells are not surviving for very long in the first 3 patients who have treatment, they will change the drugs you have. They will add in another chemotherapy drug called cyclophosphamide. You have this through a drip into a vein on the last 2 days you have fludarabine. If they do add cyclophosphamide to the treatment plan, they will remove methylprednisolone.

When you finish chemotherapy, you 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. The trial team will teach you how to give yourself the injections at home.

Hospital visits

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

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

8 weeks after having the modified T cells, you have another bone marrow test to see how the treatment has affected your leukaemia.

Side effects

When you have your T cells removed, the trial team need to use a drug called ACD-A to stop your blood clotting in the cell separator machine. This can lower the level of calcium in your blood causing symptoms such as feeling sick or a tingling sensation in your lips, nose or fingertips. If this happens, you must tell a nurse straight away. They will give you some calcium supplements and the side effects should stop once you have these.

Fludarabine can cause a drop in the number of white blood cells leading to an increased risk of infection. You take drugs to reduce the risk of bacterial and viral infections for a month after starting fludarabine.

Methylprednisolone can temporarily cause

  • An increase in your blood sugar
  • Problems sleeping

The common side effects of cyclophosphamide include

  • A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
  • Temporary hair loss
  • Feeling or being sick

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

  • High temperature (fever)
  • Aching
  • Rash
  • Wheezing or breathlessness
  • Feeling or being sick

Any treatment that stimulates your immune system can also cause less common but more serious side effects including

  • 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. If you have any problems, you should tell the trial team straight away. They will give you a phone number to contact them at any time.We have more information about

Location

Birmingham
Bristol
London

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:

10903

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

Over 60,000 cancer patients enrolled on clinical trials in the UK last year.

Last reviewed:

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