NP40126: a phase 1 trial testing a new drug given with chemo-immunotherapy for people with relapsed or refractory follicular lymphoma or untreated diffuse large B-cell lymphoma (DLBCL)

This is a phase 1 (early phase) trial of an experimental treatment. Little is known about the safety and effectiveness of this treatment. You might not benefit from the new treatment, but you also receive standard treatment as part of the trial. The trial will give important information about the experimental treatment, which could help other people in the future.

Note: Recruitment for this trial is temporarily on hold.


Purpose of trial

The aim of this trial is to find out if adding a new drug called ‘RO7082859‘ to standard treatment can make treatment work better. It is being tested as a potential treatment for people with:


Treatments

RO7082859 is a type of antibody called a ‘bispecific T-cell engager’ or BiTE. Most antibody treatments attach to one target protein but BiTEs attach to two targets (they are ‘bispecific’). RO7082859 attaches to a protein called ‘CD20’ on B cells (the type of white blood cell that is abnormal in follicular lymphoma and DLBCL). RO7082859 also attaches to a different protein called ‘CD3’ on T cells (cells of your immune system). This treatment brings T cells to the lymphoma cells so your own immune system can destroy the lymphoma.

Rituximab and obinutuzumab are antibody treatments already widely used to treat people with non-Hodgkin lymphoma. They are often used in combination with CHOP chemotherapy as a standard treatment. Antibody treatments and chemotherapy used together are called ‘chemo-immunotherapy’.

Everyone in this trial has RO7082859, CHOP chemotherapy and rituximab. Some people have obinutuzumab instead of rituximab for the first cycle of treatment. 

Most of the treatment is given intravenously (into a vein). You also take tablets. You have treatment in cycles of 3 weeks. You can have up to 6 cycles of treatment (a total of 18 weeks). 

There are 2 parts to this trial. 

In part 1, different doses of RO7082859 are being tested for people with follicular lymphoma.  Everyone has the same doses of standard chemo-immunotherapy. A few people are treated with a low dose of RO7082859 with standard chemo-immunotherapy. If this doesn’t cause troublesome problems, the next few people have a higher dose of RO7082859 with chemo-immunotherapy. This continues until the highest safe dose of RO7082859 is found. The most effective safe dose is used in the second part of the trial. 

In part 2, your treatment varies slightly depending what type of lymphoma you have. Everyone has RO7082859 at a dose selected based on the results of part 1 of the trial. Everyone has the other drugs at standard doses.

  • If you have follicular lymphoma, you have RO7082859 with obinutuzumab and CHOP for the first cycle, then you have RO7082859 with rituximab and CHOP for the next 5 cycles.
  • If you have DLBCL, you have RO7082859 with either obinutuzumab and CHOP or rituximab and CHOP for the first cycle. The antibody you have is chosen at random by computer (like tossing a coin). You then have RO7082859 with rituximab and CHOP for the next 5 cycles.

Who can enter

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

Approximately 172 people are needed for this trial.

You may be able to enter if:

  • You have follicular lymphoma and you have had at least one previous course of treatment for your lymphoma but you need more treatment.
  • You have DLBCL and you have not yet had any treatment for your lymphoma.
  • You are over 18 if you have follicular lymphoma and over 60 if you have DLBCL.
  • You are willing to have a biopsy before you start treatment in this trial.
  • Your lymphoma is measurable by the tests used in the trial.
  • You are well enough to take part in the trial.
  • Your blood and other health test results are satisfactory.

You won’t be able to enter if:

  • You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment, including an active infection, an autoimmune condition (where your body attacks itself), diabetes, heart problems or lung problems.
  • You have another cancer that could affect the results of the trial.
  • You’ve been treated with another antibody treatment, radiotherapy, chemotherapy or an experimental treatment in the last 4 weeks.
  • You’ve had major surgery in the last 4 weeks or you are expected to need major surgery during the trial.
  • You’ve had a live vaccine (for example the shingles vaccine) in the last 4 weeks or you are expected to need a live vaccine during the trial. 
  • You’ve had a bad reaction to an antibody treatment before or you are not able to have any of the treatments used in the trial.
  • You’ve already had obinutuzumab and you did not respond to it.
  • You’ve previously been treated with an anthracycline drug (a type of chemotherapy, for example doxorubicin).
  • You’ve had an organ transplant or a donor (allogeneic) stem cell transplant.
  • You’ve had a self (autologous) stem cell transplant in the last 100 days.
  • You have progressive multifocal leukoencephalopathy (a viral disease of the brain).
  • Your lymphoma is in your central nervous system (CNS; brain and spinal cord) or you have previously had lymphoma in your CNS.
  • You are taking steroids unless at a low dose.
  • You’ve ever had problems with your CNS, for example a stroke or epilepsy.
  • You have HIV, hepatitis C or hepatitis B.
  • You are pregnant or breastfeeding.

Further information

More information about this trial is available at www.clinicaltrials.gov/ct2/show/NCT03467373

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