Purpose of trial
Most people with DLBCL are treated with chemo-immunotherapy (chemotherapy with antibody therapy, such as rituximab) as first-line treatment. If DLBCL comes back or doesn’t respond to the first treatment, a different chemotherapy might be used. This second-line treatment is called ‘salvage chemotherapy’.
People who respond to salvage chemotherapy usually also have high-dose chemotherapy and a self (autologous) stem cell transplant, which uses your own stem cells to help your body recover after high doses of chemotherapy.
This trial is testing whether axicabtagene ciloleucel could be more effective than standard second-line treatment for people with relapsed or refractory DLBCL.
Axicabtagene ciloleucel is a type of treatment known as ‘CAR T-cell therapy’. This treatment uses your own immune system to try to destroy lymphoma cells. Your body produces a type of lymphocyte (white blood cell), called a T cell, to fight infections and diseases, including lymphoma. Axicabtagene ciloleucel is made from your own T cells. Your T cells are collected from your blood and genetically modified (changed) to have chimeric antigen receptors (CARs) on their surface. The modified cells are called axicabtagene ciloleucel CAR T cells. These cells are grown in the laboratory until there are enough of them to make the treatment. They are then given back to you via a vein. The axicabtagene ciloleucel CAR T cells can recognise and kill lymphoma cells that have a protein called ‘CD19’ on their surface.
This trial is randomised. If you agree to take part and you are eligible for the trial, you are randomly assigned to one of two treatment groups:
- axicabtagene ciloleucel
- standard treatment of salvage chemotherapy followed by high-dose chemotherapy and an autologous stem cell transplant (if your lymphoma is reduced by the salvage chemotherapy).
You can’t choose which treatment you have, and neither can your specialist. You are given information about both treatments and their risks and possible benefits before you agree to take part in the trial.
All treatments in the trial, including standard treatment, are given at the trial hospital.
Treatment for the axicabtagene ciloleucel group
If you are in the axicabtagene ciloleucel group, you are given the treatment if it can be successfully manufactured and you are still well enough to receive it at that time. It is not always possible to modify the T cells or produce enough axicabtagene clioleucel CAR T cells. Sometimes, lymphoma gets worse while the treatment is being manufactured and you may no longer be well enough to have axicabtagene ciloleucel. If this happens, your doctor can discuss alternative treatment options with you.
There are several treatment stages:
- Your lymphocytes are collected so that the T lymphocytes (or T cells) can be modified in the laboratory. This collection process is called ‘leukapheresis’. The T cells are modified and grown in the laboratory until there are enough cells to make the treatment.
- The week before you have the axicabtagene ciloleucel CAR T-cell treatment, you have 3 days of chemotherapy to reduce the number of white blood cells in your blood, making room for the CAR T-cell treatment cells to grow. The chemotherapy drugs are given intravenously (into a vein). You usually have this chemotherapy as an outpatient, where you don’t have to stay at the hospital overnight.
- You have a single dose of axicabtagene ciloleucel. The cells are given intravenously.
Some people have severe reactions to CAR T cells and can get very unwell. You are monitored carefully during and after the CAR T treatment to look out for this. Your medical team should discuss all the possible side effects of CAR T cells with you.
Standard treatment group
If you are having standard treatment, you have salvage chemotherapy chosen by your specialist. If your lymphoma is reduced by the salvage chemotherapy, you then have high-dose chemotherapy followed by an autologous stem cell transplant. If your lymphoma does not respond to salvage chemotherapy, you will not be able to have an autologous stem cell transplant. In this case, your specialist will discuss other treatment options with you.
An autologous stem cell transplant is needed to restore your immune system if you have high-dose chemotherapy. High-dose chemotherapy is very effective at destroying lymphoma cells, but it also destroys healthy cells. You might be unable to make the new blood cells your body needs after high-dose chemotherapy. New blood cells are made from stem cells in your bone marrow. In an autologous stem cell transplant, stem cells are taken from your body before the high-dose chemotherapy, and given back to you after you’ve had the high-dose chemotherapy.
Some people have severe side effects after a stem cell transplant and can get very unwell. You are monitored carefully during and after your treatment to look out for this. Your medical team should discuss all the possible risks with you.
Who can enter
Your consultant can give you advice on whether you might be suitable for this trial.
Approximately 350 people are needed for this trial.
You may be able to enter if:
- You have DLBCL, including transformed follicular lymphoma (tFL) (slow-growing lymphoma that has changed into DLBCL).
- You have already had one course of chemotherapy and your lymphoma did not respond (refractory lymphoma) or has come back (relapsed) within 12 months since starting treatment.
- Your first-line treatment included an anti-CD20 antibody (for example rituximab) and chemotherapy that included a type of drug called an ‘anthracycline’ (for example the CHOP combination).
- Your lymphoma is measurable by the tests used in the trial.
- You are well enough to take part in the trial.
- Your blood and other health test results are satisfactory.
- You are 18 or over.
You won’t be able to enter if:
- You’ve had more than one previous course of treatment for your DLBCL.
- You’ve had a stem cell transplant.
- You’ve had another cancer, unless you have been cured for at least 3 years or unless it is a localised cancer (your doctor can advise you if this applies to you).
- You have HIV, hepatitis B or hepatitis C.
- You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment, including heart problems, serious autoimmune problems (where your body attacks itself), 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 in the last 6 months.
- You’ve had a CAR T-cell therapy or a treatment targeting CD19 before.
More information about this trial is available at clinicaltrials.gov/ct2/show/study/NCT03391466.