IELSG 42: a phase 2 trial testing the MARIETTA regimen in people with untreated or relapsed DLBCL involving their central nervous system

This trial is testing a treatment plan for people with diffuse large B-cell lymphoma (DLBCL) growing in other parts of their bodies as well as the central nervous system (CNS). People with primary CNS lymphoma (lymphoma growing only in their CNS) are excluded from this trial.


Purpose of trial

This trial is testing whether a new treatment plan can improve the outcome for people with  diffuse large B-cell lymphoma (DLBCL) that is in your central nervous system (CNS)

DLBCL can be growing in your CNS as well as in other parts of your body when you are first diagnosed. If it relapses (comes back), it might grow in your CNS as well as other parts of your body. Your central nervous system includes your brain and spinal cord, the membranes around these, the nerves of your brain and your eyes.

Lymphoma that is in your CNS is difficult to treat.

The treatment plan in this trial includes two chemo-immunotherapy (chemotherapy with antibody therapy) regimens (combinations of drugs) given one after the other and followed by high-dose chemotherapy and a stem cell transplant using your own stem cells (autologous stem cell transplant).


Treatments

If you have a lot of lymphoma in your body and your doctor thinks you need immediate treatment, you start with 1 or 2 cycles of R-CHOP (rituximab with cyclophosphamide, doxorubicin (or hydroxydaunorubicin), vincristine and prednisolone) chemo-immunotherapy.

Other participants can start with MATRIX, as detailed below.

All participants then follow the same treatment plan.

Treatment is given in the following order:

  • MATRIX (methotrexate, rituximab, cytarabine, thiotepa) chemo-immunotherapy with intrathecal cytarabine for 3 cycles.
  • R-ICE chemo-immunotherapy (rituximab, ifosfamide, BCNU [carmustine], etoposide) with intrathecal cytarabine for 3 cycles.
  • High-dose chemotherapy (thiotepa and BCNU) and autologous stem cell transplant.

Treatment is given in cycles with treatment on some days, followed by a rest period to allow your body to recover before the next cycle. Most of your treatment is given intravenously (through a drip into a vein).

You also have intrathecal chemotherapy with each cycle of treatment, which is given by lumbar puncture into the fluid around your spinal cord.

You have scans during treatment to see how you are responding. Your doctor decides if you should continue on the trial treatment or have other treatment based on the results of your scans.

If you have some lymphoma remaining after treatment, you might be offered whole brain radiotherapy.


Who can enter

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

Around 76 people are needed for this worldwide trial; 20 are being recruited from the UK.

You may be able to enter if:

  • You have diffuse large B-cell lymphoma that involves your central nervous system.
  • You have not had previous treatment with high-dose methotrexate-based chemotherapy and/or brain radiotherapy.
  • You don’t have any other cancers.
  • You can look after yourself with some help and you are able to get up at least some of the time.
  • You and your partner are willing to use reliable contraception if there is any chance of you or your partner becoming pregnant.
  • Your blood and other health test results are satisfactory.
  • You are aged 18-70.

You will not be able to enter if:

  • You have any other type of lymphoma, including primary mediastinal lymphoma, intravascular large B-cell lymphoma or leg-type large B-cell lymphoma.
  • You have primary CNS lymphoma (lymphoma only in your CNS).
  • You’ve had a previous stem cell/bone marrow transplant.
  • You have significant heart problems.
  • You have HIV, hepatitis C or hepatitis B.
  • You have had another cancer in the last 3 years, except certain localised cancers.
  • You are pregnant or breastfeeding.
  • 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.
  • You’ve been treated with other experimental drugs within the 6 weeks prior to enrolment.

Further information

More information about this trial is available at clinicaltrials.gov.