TIDaL trial

Chief investigator - Dr Tobias Menne, Newcastle upon Tyne Hospitals
Risk-stratified sequential treatment of de-novo post-transplant lymphoproliferative disorder (PTLD) with ibrutinib (I) and rituximab (R) and IR-CHOP
Amount awarded: £168,224
Award start date: 01 Dec 2015
Recruitment start date: 01 Mar 2016
Award duration: 5 years (60 months)

Post-transplant lymphoproliferative disorders (PTLD) are a diverse group of high grade lymphomas, and are one of the most severe complications of long-term immunosuppression that happens in people who have undergone solid organ transplantation.

Currently, people are treated with a biological therapy called rituximab. Rituximab is a type of biological therapy called a monoclonal antibody. It works by targeting a protein called CD20, which is found on the surface of healthy white blood cells and abnormal white blood cells that occur in leukaemia and lymphoma. The monoclonal antibody binds to all the cells that have CD20 on their surface, which triggers the immune system to attack the marked cells and kill them. Rituximab causes both healthy and cancerous white blood cells to be destroyed, but the body can replenish the healthy white blood cells once the treatment is over.

If people do not respond adequately after 7 weeks of rituximab, they can receive additional chemotherapy called R-CHOP. This comprises: rituximab, plus the chemotherapies cyclophosphamide, doxorubicin and vincristine and also a steroid called prednisolone. Although this strategy is often successful, many people do not respond or relapse. People receiving R-CHOP are also at a higher risk of infection, and this chemotherapy can cause damage to the transplanted organ.

Ibrutinib is a relatively new drug that is widely used in certain types of lymphomas. Ibrutinib is a type of biological therapy called a Bruton’s Tyrosine Kinase (BTK) inhibitor that stops signals that cancer cells use to divide and grow. It is thought that ibrutinib may improve the response rate in people with PTLD when added to R-CHOP.

The aims of the trial are to:

  • Look at response rates, survival and safety when adding ibrutinib to R-CHOP

You may be eligible to join this trial if:

  • You have PTLD
  • You have undergone heart, lung, liver, kidney, pancreas, small intestine transplantation, or a combination of the above organ transplantations, or a stem cell transplant
  • You are at least 18 years old