A study looking at chemotherapy and targeted therapy for lymphoma of the brain or spinal cord (TIER)

Cancer type:

Blood cancers
Non-Hodgkin lymphoma




Phase 1/2

This study looked at combinations of cancer drugs for primary Open a glossary item central nervous system lymphoma. Central nervous system lymphoma is a cancer of the lymphatic system Open a glossary item that starts in the brain or spinal cord. This is CNS lymphoma. 

This trial was open for people to join between 2015 and 2019. The team published the results in 2021.

More about this trial

CNS lymphoma is usually a type of non Hodgkin lymphoma called diffuse large B cell lymphoma (DLBCL). It is a high grade lymphoma. High grade lymphomas generally grow more quickly than low grade lymphomas.

Doctors often treat CNS lymphoma with chemotherapy. Sometimes the chemotherapy doesn’t work or the lymphoma comes back after treatment. In this situation there is no standard treatment Open a glossary item. The researchers tried a new combination of the following cancer drugs:

The aims of the study were to:

  • find the best dose of thiotepa
  • see how well the combination of thiotepa, ifosfamide, etoposide and rituximab works for CNS lymphoma
  • see what the side effects of the treatment are

Summary of results

The team found that they could give thiotepa with ifosfamide, etoposide and rituximab. 

Trial design
This was a phase 1 Open a glossary item and phase 2 Open a glossary item trial. In total 36 people took part in this trial.

In phase 1 the first few people had a small dose of thiotepa with
ifosfamide, etoposide and rituximab. If all went well then the next few had a higher dose of thiotepa. And so on until the team found the best dose of thiotepa to give with ifosfamide, etoposide and rituximab. 

In phase 2 everyone had this dose of thiotepa with ifosfamide, etoposide and rituximab. 

The research team wanted to find out how well this combination had helped. To do this they looked at what the intention to treat was when people joined the trial. This is called an intention to treat analysis Open a glossary item. For this analysis there were 27 people. They found that it helped 14 people (52%). 

Of these 14 people:

  • there was no sign of the lymphoma in 9 (a complete response)
  • the lymphoma had got better in 5 (a partial response)

The lymphoma had got worse in 4 people. This is called progressive disease. 

The team were unable to include the remaining 9 people for a number of reasons. They include:

  • death 
  • leaving the trial
  • stopping treatment due to side effects

The team looked at the length of time people lived without any sign of the lymphoma getting worse. They found it was from 2 months to 6 months. 

They also looked at the length of time that people lived after treatment. They found it was from 3 months to 9 months. 

Side effects
The team looked at the worst side effects of treatment. The most common of these included:

  • a drop in blood cells causing an increased risk of bruising, bleeding and infection
  • a high temperature (fever) with a low number of white blood cells called neutrophils Open a glossary item
  • fits (seizure)
  • confusion
  • difficulty speaking
  • headache
  • low levels of phosphate, potassium, magnesium and albumin in the blood
  • difficulty swallowing 

The team concluded that thiotepa, ifosfamide, etoposide and rituximab can help people with CNS lymphoma:

  • that has come back after treatment or 
  • when initial chemotherapy doesn’t work 

However they say that for most people the outcome of treatment remains poor and new treatment plans are urgently needed. 

Where this information comes from
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Professor Christopher Fox

Supported by

Experimental Cancer Medicine Centre (ECMC)
University of Birmingham

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:


Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Wendy took part in a new trial studying the possible side effect of hearing loss

A picture of Wendy

"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”

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