TIER trial

Chief investigator - Dr Christopher Fox, Nottingham University Hospitals NHS Trust
Cancer type - Lymphoma
A phase I/II study of thiotepa, ifosphamide, etoposide and rituximab for the treatment of relapsed and refractory primary central nervous system lymphoma
Award start date: 01 Jan 2014
Recruitment start date: 03 Feb 2015
Award duration: 5 years

Primary central nervous system lymphoma (PCNSL) is a rare type of high-grade non-Hodgkin lymphoma that only affects the central nervous system (CNS), which means the brain, eye and spinal cord.

People with PCNSL are usually treated with chemotherapy. But sometimes the lymphoma does not respond to chemotherapy, or it comes back after treatment. In this situation there is no standard treatment, so we need to find new ways to treat this group of people.

Researchers want to try a new combination of cancer drugs comprising of chemotherapies and a biologic drug. The following drugs will be tested: thiotepa, ifosfamide, etoposide and rituximab.

Thiotepa, ifofamide and etoposide are chemotherapies. Thiotepa and ifosfamide work by interfering with the cancer cell’s DNA, preventing the cells from growing and dividing. Etoposide works by blocking an enzyme called topoisomerase 2, which is necessary for cancer cells to divide.

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.

The aims of the study are to:

  • Discover the best dose of thiotepa
  • See how well the combination of thiotepa, ifosfamide, etoposide and rituximab works for PCNSL

You may be eligible to join this trial if:

  • You have DLBCL that started in your brain and spinal cord, which has come back after previous treatment or has not responded to treatment
  • You are at least 16 years old