TIER: a phase 2 trial of the TIER regimen of chemotherapy and rituximab antibody therapy in people with relapsed or refractory primary central nervous system lymphoma

This trial is testing whether a new chemo-immunotherapy (chemotherapy with antibody therapy) regimen (combination of drugs) can help people with primary central nervous system lymphoma who have had treatment but who need more treatment.. 

Purpose of trial

Lymphoma that starts in your brain or spinal cord is called primary central nervous system (CNS) lymphoma (PCNSL). It is usually a type of diffuse large B-cell lymphoma.

PCNSL is usually treated with chemotherapy, but there is no standard treatment if the lymphoma relapses (comes back) or is refractory (doesn’t respond) to the first treatment. This trial aims to find out if the TIER regimen is safe and effective for people with relapsed or refractory PCNSL. 


Everyone in this trial has the TIER regimen, which includes:

  • chemotherapy drugs: thiotepa, ifosphamide, etoposide
  • antibody therapy: rituximab.

There are 2 parts to the trial:

  • Part 1 is to find out the highest safe dose of the drugs. This is done by ‘dose escalation’. Participants are treated in groups of 3. The first 3 participants have the lowest dose. The next 3 have a higher dose and so on. Participants are monitored carefully for side effects. The highest dose that doesn’t cause serious side effects is used in part 2 of the trial.
  • Part 2 is to test how well the treatment works. This part includes people from part 1 who were treated with the highest safe dose and additional people who are treated at the highest safe dose from part 1. Note: Part 1 is now closed but new participants can enter part 2 of the trial.

The drugs are given in 3-week cycles for 2 cycles. You have treatment for 5 days followed by a rest period for your body to recover. You have all of the drugs intravenously (into a vein).

After the trial, you might have 2 further cycles of the chemotherapy drugs (thiotepa, ifosphamide and etoposide). Your doctor might then recommend high-dose therapy and a stem cell transplant or radiotherapy.

Who can enter

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

Around 40 people are needed for this trial

You may be able to enter if:

  • You have primary CNS lymphoma - diffuse large B-cell lymphoma that is only in your CNS.
  • You have previously been treated with a regimen containing the drug methotrexate and the lymphoma has relapsed or was refractory.
  • You can look after yourself with some or no help and you are able to get up at least some of the time.
  • Your blood and other health test results are satisfactory.
  • You and your partner are willing to use reliable contraception during treatment and for at least 12 months after 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:

  • The lymphoma is also outside of your CNS.
  • You have an infection that needs intravenous treatment.
  • You’ve had chemotherapy for lymphoma in the last 4 weeks.
  • You’ve had whole-brain radiotherapy in the last 6 months.
  • You’ve had an autologous stem cell transplant with thiotepa in the last year.
  • You’ve had previous treatment with the R-IE regimen (rituximab, ifosphamide and etoposide).
  • You have HIV or hepatitis B or C.
  • You are pregnant or breastfeeding.

Further information

More information about this trial is available at Cancer Research UK