LOTIS-3: A phase 1/2 trial of loncastuximab tesirine and ibrutinib in people with relapsed or refractory diffuse large B-cell lymphoma or mantle cell lymphoma

This trial is testing a new treatment called loncastuximab tesirine, combined with ibrutinib, in people with DLBCL or mantle cell lymphoma that has not responded (refractory) or has come back (relapsed) after previous treatment.


Purpose of trial

The aim of this trial is to test how safe and effective loncastuximab tesirine is when it is combined with ibrutinib.


Treatments

The trial is in two parts:

  • Part 1 is to find out the highest safe dose of loncastuximab tesirine when it is combined with ibrutinib. This is done by ‘dose escalation’. Participants are treated in groups. The first few participants have the lowest dose of loncastuximab tesirine. They have blood tests to measure the level of the drug in their body and they are carefully monitored for side effects. If the lowest dose doesn’t cause troublesome problems, the next few participants have a higher dose. This continues until the highest safe dose is found. The most effective safe dose is used in the second part of the trial. This part is complete.
  • Part 2 is to test how well the highest safe dose of loncastuximab tesirine combined with ibrutinib works. People entering this part of the trial all have the same dose of loncastuximab tesirine.

Loncastuximab tesirine is a type of targeted treatment called an antibody–drug conjugate: an antibody joined to a toxic drug. The antibody sticks to a protein called CD19 found on the surface of some lymphoma cells, and carries the drug straight to them. The drug is released inside the cells and kills them.

You have it through a drip into your vein (intravenously) once every 3 weeks. It takes around 30 minutes for the drug to be given. You have up to 6 cycles of treatment, depending on your response.

Ibrutinib is a cell signal blocker. It blocks signals that encourage lymphoma cells to grow. It is already used to treat some types of lymphoma. You have it as a capsule that you take by mouth every day. You carry on taking it for up to 1 year, as long as the treatment is benefitting you and any side effects are manageable. There might be an option to continue for longer for some people.


Who can enter

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

Around 161 people are needed for this trial.

You may be able to enter if:

  • You have diffuse large B-cell lymphoma (DLBCL) that has not responded to, or has come back after, standard treatment options.
  • You have mantle cell lymphoma that has not responded to, or has come back after, at least one previous course of treatment.
  • If you’ve had treatment that targets a protein called CD19 (for example, CAR T-cell therapy), your lymphoma cells still make that protein.
  • Your lymphoma is measurable by the tests used in the trial.
  • You have a recent biopsy sample available.
  • You are well enough to take part in the trial.
  • Your blood and other health test results are satisfactory.
  • You and your partner are willing to use reliable contraception if there is any chance of you or your partner becoming pregnant.
  • You are 18 or over.

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 significant heart disease, lung disease or infections.
  • Your lymphoma is in your central nervous system (CNS; brain and spinal cord).
  • You have post-transplant lymphoproliferative disorder (PTLD).
  • You have an autoimmune condition.
  • You have a bleeding disorder.
  • You have HIV, hepatitis C or hepatitis B.
  • You have another cancer, except certain localised cancers.
  • You have ever had a rare skin condition called Stevens-Johnson syndrome or toxic epidermal necrolysis.
  • You have significant side effects from your previous treatment.
  • You’ve had an autologous stem cell transplant or allogeneic stem cell transplant in the last 2 months.
  • You have active graft versus host disease.
  • You have fluid on your lungs or in your tummy that needs draining.
  • You’ve had major surgery, radiotherapy, chemotherapy, treatment as part of another clinical trial, or any other cancer treatment in the past 2 weeks.
  • You are taking medication to thin your blood (except low-dose heparin).
  • You are taking certain other drugs that might interfere with the study treatment.
  • You are scheduled to have a live vaccine after starting the trial.
  • You have been treated with a similar drug before.
  • You are pregnant or breastfeeding.
  • You’ve had a bad reaction to CD19 antibodies or ibrutinib in the past.

Further information

More information about this trial is available at https://clinicaltrials.gov/ct2/show/NCT03684694