TIDaL: a phase 2 trial of ibrutinib with rituximab for people with post-transplant lymphoproliferative disorder

This trial is testing whether adding ibrutinib to rituximab can improve treatment for PTLD.


Purpose of trial

Post-transplant lymphoproliferative disorder (PTLD) is a type of lymphoma that can develop in people with weakened immune systems after an organ transplant or donor (allogeneic) stem cell transplant.

Rituximab on its own can be an effective treatment for some people with PTLD.

The majority of people do not respond well to rituximab and need more intensive (stronger) treatment with R-CHOP (CHOP chemotherapy with rituximab).

R-CHOP is often very effective but can cause serious side effects and can damage the transplanted organ.

The aim of this trial is to test whether adding ibrutinib to the standard treatment of rituximab can reduce the number of people who then need R-CHOP. If adding ibrutinib to rituximab is safe and effective, fewer people will need more intensive treatment.


Treatments

Rituximab is an antibody therapy that is already widely used to treat many types of lymphoma.

Ibrutinib is a newer drug that blocks signals that help cancer cells stay alive. It is already in routine use for some types of lymphoma.

R-CHOP is rituximab with the chemotherapy drugs cyclophosphamide, hydroxydaunorubicin, and Oncovin® and the steroid prednisolone.

Everyone in this study has rituximab and ibrutinib.

You take ibrutinib by mouth as capsules once a day every day for 7 weeks. You have rituximab intravenously (into a vein) once a week for 4 weeks.

You have a CT scan 7 weeks after starting treatment, which is used to decide what treatment you need next.

People who responded well to the treatment continue to take ibrutinib for a further 12 weeks and have rituximab once every 3 weeks for four more doses. Each 3-week period is a cycle of treatment.

People whose PTLD has not shrunk enough on the scan also continue with ibrutinib and rituximab, but have 4 cycles of CHOP alongside this. This treatment is called ‘IR-CHOP’. If you are having IR-CHOP, you are given chemotherapy drugs once every 3 weeks on the same day that you have rituximab. You also take prednisolone tablets for the first 5 days of each cycle.

If your PTLD gets worse at any time during treatment, you start IR-CHOP immediately.


Who can enter

Your consultant can give you advice on whether this trial might be suitable for you.

Up to 60 people are needed for this trial.

You may be able to enter if:

  • You have PTLD and the abnormal cells have CD20 (the target for rituximab).
  • You have had a heart, lung, liver, kidney, pancreas or small intestine transplant, or a combination of these or you have PTLD after an allogeneic stem cell transplant or your PTLD is affecting your central nervous system (CNS; brain and spinal cord).
  • Your blood and other health test results are satisfactory.
  • Your lymphoma is measurable by the tests used in the trial.
  • You are well enough to look after yourself and are up and about more than 50% of your waking hours, even if you are not well enough to work.
  • Your PTLD did not respond well to reducing your immunosuppressive drugs (drugs that dampen down your immune system).
  • You and your partner are willing to use reliable contraception during the trial and for at least 12 months after completing the trial treatment if there is any chance of you or your partner becoming pregnant.
  • You are 16 or over.

You will not be able to enter if:

  • Your PTLD can be removed completely by surgery or is suitable for radiotherapy.
  • You have had treatment with chemotherapy, rituximab or another antibody therapy.
  • You have severe problems with your organs that are not related to PTLD.
  • You have T-cell PTLD (lymphoma that has developed from an abnormal T cell).
  • You need treatment with other drugs that could interfere with the study treatment.
  • You have been treated with blood-thinning drugs, for example warfarin, in the last week.
  • You have HIV, hepatitis B or another severe, active infection.
  • You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment.
  • Any of the study drugs are not suitable for you.

Further information

More information about this trial is available on the UK clinical trials gateway.