Purpose of trial
The aim of this trial is to find out more about a new type of treatment, AUTO4 CAR-T cells, in people with T-cell lymphomas.
T-cell lymphoma commonly relapses, and relapsed or refractory T-cell lymphoma is often difficult to treat. This trial is testing whether AUTO4 CAR-T cells are safe and effective for people who have had previous treatment for T-cell lymphoma but need more treatment.
The trial aims to find out:
- if AUTO4 CAR-T cells are safe for people with T-cell lymphoma
- what the most effective, safe dose of AUTO4 CAR-T cells is (how many AUTO4 CAR-T cells you should be given)
- how effective AUTO4 CAR-T cells are in treating T-cell lymphoma.
This treatment uses your own immune system to try to destroy lymphoma cells. Your body produces a type of lymphocyte, called a T cell, to fight infections and diseases, including lymphoma. In T-cell lymphoma, the type of cell that has become cancerous (growing out of control) is a T cell (or ‘T lymphocyte’).
AUTO4 CAR-T cells are made from your own healthy T cells. Your T cells are collected from your blood and genetically modified (changed) to have chimeric antigen receptors (CARs) on their surface. The genetically modified T cells (CAR-T cells) are grown in the laboratory until there are enough of them. They are then given back to you.
All cells in your body have receptors on their surface to enable the cells to function normally and communicate with the rest of your body. All T cells naturally produce one of two T-cell receptors at random: ‘TRBC1’ or ‘TRBC2’. Cancerous T cells only produce one of the two T-cell receptors. The CARs used in AUTO4 CAR-T cells recognise and kill cells with TRBC1 on their surface. Therefore AUTO4 CAR-T cells can only be used for people whose lymphoma cells produce TRBC1.
Lymphoma cells from your biopsy are tested to find out if they have TRBC1 or TRBC2. If your biopsy is tested and your lymphoma cells have TRBC1 then you will be considered for the trial. Healthy T cells that have TRBC1 will also be killed by AUTO4 CAR-T cells but you will still have healthy T cells that have TRBC2 in your body to help your immune system work.
CAR-T cells can be very effective treatments but can also produce life-threatening side effects. As CAR-T cells multiply in your body, these side effects can be difficult to control. AUTO4 CAR-T cells have an ‘off switch’ built into them called ‘RQR8’. If you have serious problems, you can be given a drug called rituximab, which is given intravenously (into a vein). It attaches to the RQR8 switch, which then sends a signal for the AUTO4 CAR-T cells to self-destruct. It therefore stops AUTO4 CAR-T cells from causing any further side effects.
Everyone in this trial receives AUTO4 CAR-T cells if they can be successfully manufactured. It is not always possible to modify the T cells or produce enough AUTO4 CAR-T cells. If this happens, your doctor can discuss alternative treatment options with you.
There are several treatment stages in this trial:
- Your lymphocytes are collected at the hospital so that the T lymphocytes (or T cells) can be modified at the sponsor’s manufacturing site. This collection process is called ‘leukapheresis’. The T cells are modified and grown in the manufacturing site until there are enough cells to make the treatment.
- The week before you have the AUTO4 CAR-T cells, you have chemotherapy with cyclophosphamide and fludarabine. This chemotherapy is called pre-conditioning. These drugs are given intravenously (into a vein). The pre-conditioning chemotherapy is given over 3 days the week before the AUTO4 CAR-T cell infusion.
- You have a single dose of AUTO4 CAR-T cells. The cells are given intravenously and usually take a few minutes to infuse.
You are monitored carefully in hospital during and after the treatment. You must still be well enough to have the AUTO4 CAR-T cell treatment when it is ready. If you are not well enough to continue in the trial, your doctor might delay your treatment or discuss other treatment options with you.
There are two parts in this study. You enter either part 1 or part 2.
- In part 1, several different doses of AUTO4 CAR-T cells are being tested. The first few participants have the lowest dose being tested. If this doesn’t cause troublesome problems, the next few people have a higher dose. If the higher dose doesn’t cause troublesome problems, the last few people have the highest dose.
- In part 2, the safest and most effective dose from part 1 of the trial is tested in more people.
You have regular blood tests after treatment to see how it is affecting your body and the lymphoma.
Who can enter
Your consultant can give you advice on whether you might be suitable for this trial.
Approximately 55 people are needed for this trial in the UK.
You may be able to enter if:
- You have peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) or anaplastic large cell lymphoma (ALCL).
- Your lymphoma cells have TRBC1.
- Your lymphoma has come back, or treatment has stopped working (relapsed or refractory).
- You have already had at least one course of treatment.
- Your lymphoma is measurable by the tests used in the trial.
- You are able to have your T cells collected.
- You are well enough to take part in the trial.
- Your blood and other health test results are satisfactory.
- Your kidneys, liver, heart and lungs are working well.
- You are willing to use reliable contraception during treatment and females are willing to continue to use contraception for at least 12 months after treatment.
- You are 18 or over.
You won’t be able to enter if:
- You have T-cell leukaemia.
- You have been treated with another gene therapy or you’ve had a donor (allogeneic) stem cell transplant.
- You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment, including heart problems, high blood pressure, lung problems, serious autoimmune problems (where your body attacks itself), blood clots, bleeding in your digestive system, or an active infection.
- Your lymphoma is in your central nervous system (CNS; brain and spinal cord) or you have previously had any cancer in your CNS.
- You’ve ever had problems with your CNS, for example brain injuries, dementia or epilepsy.
- You’ve had a blood clot requiring blood thinning medicines in the last 3 months.
- You’ve had major surgery in the last 3 months.
- You’ve had another cancer unless you have been cured for at least 2 years or unless it is a localised cancer (your doctor can advise you if this applies to you).
- You’ve had treatment with drugs that target the programmed cell death 1 protein (PD1), the PDL1 or the CTLA-4 protein (your doctor can tell you more about this).
- You’ve had a bad reaction to treatments targeting CD19 or CD22 before.
- You are taking certain medicines (ask your doctor for advice).
- You’ve had chemotherapy or antibody therapy in the last 2 weeks, high doses of steroids in the last 3 days or a live vaccine in the last 4 weeks.
- You are being treated with another experimental treatment or you are taking part in another clinical trial.
- You’ve had rituximab or any other similar drug in the last 3 months.
- You are pregnant or breastfeeding.
More information about this trial is available at clinicaltrials.gov/ct2/show/NCT03590574