COBALT: a phase 1 trial testing CD19 CAR-T cells as treatment for people with diffuse large B-cell lymphoma (DLBCL) that has relapsed (come back) or was refractory (didn’t respond) to previous treatment

This is a small phase 1 (early phase) trial of an experimental treatment. Little is known about the safety and effectiveness of this treatment. 


Purpose of trial

The aim of this trial is to find out more about a new type of treatment, CD19 CAR-T cells, in people with diffuse large B-cell lymphoma (DLBCL) who have had previous treatment and now need a donor (allogeneic) stem cell transplant.

If DLBCL relapses (comes back), it might be treated with more intensive chemotherapy and a self (autologous) stem cell transplant, which uses your own stem cells to help your body recover after high doses of chemotherapy. Some people can’t have an autologous stem cell transplant because the lymphoma does not respond sufficiently to chemotherapy. Sometimes lymphoma comes back again after an autologous stem cell transplant. In both cases, treatment can be very difficult.

Some people are candidates for an allogeneic stem cell transplant, where stem cells come from a donor (someone else). This treatment only works well in people responding to treatment.

This trial is testing whether CD19 CAR-T cells can reduce the amount of lymphoma before an allogeneic stem cell transplant. The trial aims to find out:

  • if CD19 CAR-T cells are safe for people with DLBCL
  • what the most effective safe dose is
  • how effective the treatment is
  • whether people treated with CD19 CAR-T cells can go on to have an allogeneic stem cell transplant.

Treatments

This treatment uses your own immune system to try to destroy lymphoma cells.

CD19 CAR-T cells are a type of immune cell, called a T cell, which has been altered to express a chimeric antigen receptor (CAR).

Your T cells are collected from your blood and genetically modified (changed) to recognise and kill lymphoma cells with CD19 (a type of protein) 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.

Everyone in this trial receives CD19 CAR-T cells if they can be successfully manufactured.

It is not always possible to modify the T cells or produce enough CD19 T cells. If this happens, your doctor can discuss alternative treatment options with you.

There are several stages in the treatment:

  • Your lymphocytes (a type of white blood cell) are collected so that the T lymphocytes (or T cells) can be modified in the laboratory. The collection process is called ‘leukapheresis’.
  • While the T cells are being modified, you have a cycle of chemotherapy, usually IVE (ifosfamide, epirubicin and etoposide) but your doctor might suggest a different regimen (combination of drugs).
  • The week before you have the CD19 CAR-T cells, you have chemotherapy with cyclophosphamide and fludarabine. These drugs are given intravenously (into a vein). You have the drugs over 7 days.
  • You have one dose of CD19 CAR-T cells. The cells are given intravenously).

Up to three different doses of CD19 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.

You are monitored carefully during and after the treatment. This is because some people have severe reactions and can get very unwell.

You have regular blood tests after having the CD19 CAR-T cells to see how they are affecting your body and the lymphoma.

If your lymphoma responds to the treatment, you may be able to have an allogeneic stem cell transplant.

Who can enter

Referrals for this study must come from your current doctor, who can liaise with the trial team at University College London Hospital (UCLH) for advice on whether you are suitable for this trial and whether any other conditions or treatments you have or have had prevent you from entering the trial. If you are interested in taking part, you should discuss the trial with your current doctor in the first instance.

The trial is recruiting 12 people.

You may be able to enter if:

  • You have DLBCL that has CD19 (the target for the modified T cells).
  • Your DLBCL has relapsed after an autologous stem cell transplant and you are not responding to chemotherapy or you did not respond to chemotherapy and therefore can’t have an autologous stem cell transplant.
  • You are fit enough for an allogeneic stem cell transplant.
  • Your blood and other health test results are satisfactory.
  • You are willing to use reliable contraception throughout the trial and for 12 months after the CD19 T cell treatment.
  • You are aged 16–65.

You will not be able to enter if:

  • You have already had an allogeneic stem cell transplant.
  • Your DLBCL has progressed (gotten worse) after your most recent chemotherapy.
  • You have heart problems.
  • You are not a candidate for an allogeneic stem cell transplant.
  • You have lymphoma affecting your central nervous system (CNS; brain and spinal cord) or you have had a stroke in the last 3 months.
  • You are being treated with steroids unless it’s at a low dose.
  • You have been treated with rituximab in the 2 months before CD19 T cell infusion.
  • You have an autoimmune disease (where your body attacks itself) and need immunosuppressive drugs (drugs that dampen down the immune system).
  • You are allergic to any of the ingredients in the trial treatment.
  • You can’t have any of the chemotherapy drugs used in the trial.
  • You have hepatitis B, hepatitis C or HIV.
  • You are pregnant or breastfeeding.
  • You have any other problems that your doctor thinks make it unsafe for you to have the study treatment.

Further information

More information about this trial is available at Cancer Research UKNote: You can only enter this trial if you are referred by your doctor. You can discuss this information with your doctor if you think you might be eligible.