A trial of CAR T-cell for people with T cell lymphoma (AUTO4-TL1)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Blood cancers

High grade lymphoma

Lymphoma

Non-Hodgkin lymphoma

Secondary cancers

Status:

Closed

Phase:

Phase 1/2

This trial is for people with T cell lymphoma that:

has come back or got worse (relapsed)
treatment has stopped working (refractory)

It is for people who have proteins called TRBC1 on the surface of their lymphoma cells (TRBC1 positive).

More about this trial

T cell lymphoma is a type of high grade non Hodgkin lymphoma (NHL) that affects immune system cells called T cells.

There are different types of T cell lymphomas. The most common type is peripheral T cell lymphoma. Rarer types include:

anaplastic large cell lymphoma
angioimmunoblastic T cell lymphoma

Some T cell lymphomas have a protein called TRBC1 on their surface.

Chemotherapy is a common treatment for T cell lymphoma. But sometimes, the lymphoma continues to grow or comes back after treatment has finished. You may have more chemotherapy if this happens.

Researchers are looking at new ways to help people with relapsed or refractory T cell lymphoma. In this trial, they are looking at a new treatment called CAR T-cell.

CAR T-cell treatment uses the T cells from your immune system. These cells are good at helping us fight infections, but they aren’t so good at recognising lymphoma cells.

With this treatment, doctors collect your T cells and change them in the laboratory so that they recognise and attack the lymphoma cells that have the TRBC1 protein. These altered T cells are called AUTO4.

This trial is in 2 parts. In part 1 doctors are looking for the best dose of AUTO4. This part is called dose escalation. In part 2, they will collect information about how well the treatment works. This is the dose expansion part.

Please note – doctors are currently looking for people to join part 1.

The main aims of this trial are:

find out the best dose of AUTO4 treatment
learn more about the side effects
find out how well AUTO4 treatment works for people with relapsed or refractory T cell lymphoma

Who can enter

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial 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 join this trial if all of the following apply:

you have T cell non Hodgkin lymphoma (peripheral T cell lymphoma, anaplastic large cell lymphoma or angioimmunoblastic T cell lymphoma)
your T cell lymphoma has TRBC1 proteins on its surface (TRBC1 positive)
your lymphoma has come back or treatment has stopped working (relapsed or refractory)
you have had at least one treatment for T cell lymphoma
you have lymphoma that can be seen on a PET scan
you are able to have your T cells collected
you have satisfactory blood tests results
your kidneys, liver, heart and lungs are working well
you are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
you are at least 18 years old
you are willing to use reliable contraception during treatment and for up to a year afterwards if there is any possibility that you or your partner could become pregnant

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related

You:

have T cell leukaemia
have lymphoma spread in your brain or the spinal cord
have had gene therapy
have had a stem cell transplant from a donor (allogeneic stem cell transplant)
have had treatment with drugs that target the programmed cell death 1 protein (PD1), the PDL1 or the CTLA-4 protein in the last 6 weeks (your doctor can tell you more about this)
have had chemotherapy in the past 2 weeks
have had rituximab or any other similar drug in the last 6 months
are having radiotherapy or a targeted cancer drug (biological therapy)
have had another cancer in the last 2 years apart from non melanoma skin cancer or carcinoma in situ of the breast or prostate that has been successfully treated

Medical conditions

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

are having an investigational treatment
have problems with your brain, spinal cord and nerves such as epilepsy
have had a stroke in the past 3 months
have heart problems such as angina that isn’t stable, an abnormal heart rhythm, high blood pressure that isn’t controlled or you have had a heart attack in the last year
have had problems with blood clots in your legs in the past 3 months and you are having treatment for this
have a bleed in your tummy (abdomen)
have had major surgery in the last 3 months
have an infection that needs treatment
have taken steroids within 3 days of having CAR T-cell treatment
have HIV
have hepatitis B or hepatitis C
have an autoimmune disease and you need to take drugs that damp down your immune system (immunosuppressants)
have any other serious medical condition or mental health problem that the trial team think could affect you taking part

Other

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

have had a live vaccine in the last month
are pregnant or breastfeeding

Trial design

This is a phase 1/2 trial. It is in 2 parts:

dose escalation (part 1)
dose expansion (part 2)

In part 1 doctors are looking for the best dose of AUTO4. They hope that around 25 people will agree to take part.

Part 2 starts when doctors find the best dose of AUTO4. They give the best dose found in part 1 to more people. Doctors hope that up to 30 people will join the second part of this trial.

Please note – doctors are currently looking for people to join the 1st part of this trial.

There are 4 steps in this trial:

biopsy
collection of white blood cells (leukapheresis)
chemotherapy
having the changed white blood cells back (AUTO4 treatment)

Biopsy

Your doctor asks to use a sample of your cancer taken when you had a biopsy. You might need to have a new sample taken if there isn't a suitable sample available. Doctors want to check whether there are TRBC1 proteins on the surface of the lymphoma cells.

Your doctor will tell you more about having a biopsy. How you have this depends on your individual situation.

If your lymphoma does not have TRBC1 proteins on its surface (TRBC1 negative), you can’t continue taking part in the trial. Your doctor will tell you about other treatments that you may be able to have.

You continue this trial if your lymphoma has TRBC1 proteins on its surface (TRBC1 positive). You have more tests such as blood tests and a CT scan to check that you meet all the other entry conditions of this trial.

Collection of white blood cells (leukapheresis)

Leukapheresis is a procedure to collect white blood cells from your bloodstream.

You lie on a bed or reclining chair and have a tube into a vein in your arm. The tube takes the blood and puts it through a machine that separates the T cells (white blood cells) from the blood. The rest of your blood goes back to your body.

Researchers in the laboratory modify and grow your T cells to recognise and attack the lymphoma cells. It usually takes between 4 to 6 weeks to do this.

It isn’t always possible to collect enough T cells during leukapheresis. You may have this procedure twice if this happens.

Sometimes, researchers can’t grow enough T cells in the laboratory. Your doctor will talk to you about other treatment that you might be able to have if this happens.

Chemotherapy

A week before you have the AUTO4 treatment, you have chemotherapy. This helps the changed T cells to survive and grow inside the body:

The chemotherapy treatment you have includes:

You have both drugs as a drip into your bloodstream (intravenously). You have this the week before your AUTO4 treatment.

Having the changed white blood cells back (AUTO4 treatment)

You have the changed T cells back as a drip into your vein. It takes about 30 minutes to have it. The trial team can tell you if this applies to you.

You need to stay in hospital after having the AUTO4 treatment. This is so doctors can monitor you for any side effects. They will tell you how many days you need to stay in hospital for. This is usually at least 2 weeks.

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Hospital visits

You see a doctor and have some tests before you take part. The tests might include:

physical examination
blood tests
heart trace (ECG)
heart scan (echocardiogram] or MUGA)
CT scan or MRI scan
PET scan

It takes between 4 and 6 weeks to change and grow the T cells in the laboratory. The trial team will tell you when you need to go back to hospital for your chemotherapy.

You need to stay in hospital for at least 2 weeks after having the AUTO4 treatment, or until your doctors think you are well enough to go home. They will monitor you during this time for any side effects you might have.

After treatment, you see the trial doctors regularly for up to 2 years. This is called follow up. Initially, you see them every week for the first month. You then see them:

every month for 6 months
then every 3 months for a year
then every 6 months

During each visit you have blood tests and a physical examination. You also have a CT scan and PET scan at set times during the follow up.

Side effects

CAR T-cell treatment is new, so there may be side effects we don’t know about yet. The trial team will monitor you during the time you have treatment and afterwards. You have a phone number to call if you are worried about anything.

The possible side effects of a biopsy are:

bruising, bleeding and pain at the site of biopsy
infection

The possible side effects of leukapheresis are:

feeling light headed
twitching muscles and cramps
tingling around the lips, nose or fingertips
bruising

The most common side effects of cyclophosphamide and fludarabine are:

high temperature (fever)
inflammation of the bladder
hair loss or hair thinning
blood in the urine
a drop in the levels of red blood cells, white blood cells and platelets causing an increased risk of infection, breathlessness and bleeding
cough
feeling or being sick
loose or watery poo (diarrhoea)
tiredness (fatigue)

A possible side effect of the AUTO4 treatment is called cytokine release syndrome (CRS). AUTO4 can cause the release of chemicals called cytokines. The side effects of the release of cytokines can be mild or severe. Side effects include:

high temperature
aching muscles
flu like symptoms
difficulty breathing
problems with your blood clotting
low blood pressure

Other side effects of the AUTO4 treatment include:

confusion
difficulty speaking and writing
fits (seizures)
an increased risk of infection
damage to the kidneys
an increased risk of developing another cancer some years after treatment has finished

We have more information about the possible risks of: