Purpose of trial
The aim of this trial is to find out whether JCAR017 (a CAR T-cell therapy) is safe and effective for adults who have relapsed or refractory diffuse large B-cell lymphoma (including DLBCL that was originally diagnosed as a different type of lymphoma but transformed (changed) into DLBCL) or certain other high-grade (fast-growing) B-cell non-Hodgkin lymphomas, including double-hit lymphoma, triple-hit lymphoma, grade 3 follicular lymphoma and primary or secondary central nervous system 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. JCAR017 CAR T cells are 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 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. The JCAR017 CAR T cells can recognise and kill lymphoma cells with a protein called CD19 on their surface.
Everyone in this trial receives JCAR017 CAR T cells if they can be successfully manufactured. It is not always possible to modify the T cells or produce enough JCAR017 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 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. During this time, you may need to have chemotherapy. Your doctor will talk to you about the best option for you.
- If the laboratory can make enough JCAR017 CAR T-cells, you have the chemotherapy drugs fludarabine and cyclophosphamide every day for 3 days. They are given intravenously (through a drip into your vein).
- Between 2 and 7 days later, you are given the JCAR017 CAR T cells. The cells are given intravenously (through a drip into your vein).
You are monitored carefully during and after the treatment. This is because some people have severe reactions to CAR T cells and can get very unwell. Your medical team should discuss all the possible side effects of CAR T cells with you.
You are followed-up for at least 2 years after the 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.
Around 124 people are needed for this trial.
You may be able to enter if:
- You have: high-grade diffuse large B-cell lymphoma (DLBCL) that can’t be classified as anything else (DLBCL not otherwise specified, or NOS), including DLBCL that was originally diagnosed as a different type of lymphoma but transformed (changed) into DLBCL; fast-growing (grade 3) follicular lymphoma; double-hit lymphoma; triple-hit lymphoma; or primary central nervous system lymphoma.
- You have previously had at least one course of treatment for your lymphoma. Depending on the type of lymphoma you have, you may need to have had at least two previous courses of treatment and your treatment may need to have included certain drugs (your doctor can tell you if this applies to you).
- You have had a biopsy of your lymphoma since your last treatment.
- 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.
- Your veins are suitable for the process used to collect your lymphocytes (your doctor can check this).
- You and your partner are willing to use reliable contraception if there is any chance of you or your partner becoming pregnant.
- You are 18 or over.
You won’t be able to enter if:
- You have T cell/histiocyte-rich large B-cell lymphoma, primary cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma, Epstein Barr virus-positive DLBCL of the elderly, or Burkitt lymphoma.
- You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment.
- You have chronic graft-versus-host disease.
- You have HIV, hepatitis C or hepatitis B.
- 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 heart disease in the last 6 months.
- You’ve ever had an illness affecting your central nervous system (apart from CNS lymphoma) – for example brain injuries, stroke, dementia or epilepsy.
- You have an autoimmune disease that is being treated with drugs that suppress your immune system.
- You have an infection that doesn’t go away with treatment.
- You are taking or have taken certain other drugs (your doctor can advise you if this applies to you).
- You’ve had radiotherapy in the last 6 weeks.
- You’ve had donor lymphocytes (white blood cells) in the last 6 weeks.
- You’ve had an allogeneic (donor) stem cell transplant in the last 90 days.
- You’ve had gene therapy in the past.
- You are pregnant or breastfeeding.
More information about this trial is available at clinicaltrials.gov/ct2/show/NCT03484702.