FUSION NHL001: a phase 1 / 2 trial aiming to find the maximum safe dose and the possible side effects of a drug called durvalumab for B cell lymphoma or chronic lymphocytic leukaemia (CLL) that has come back or is difficult to treat

This trial is testing a new treatment option for people whose B-cell lymphoma or chronic lymphocytic leukaemia (CLL) has come back or is not responding to treatment. 


Purpose of trial

The aim of the trial is to investigate a new drug called durvalumab and find out:

  • the best dose of other drugs in combination with durvalumab for treating lymphoma
  • what the possible side effects are
  • how well it works for CLL or B cell lymphomas that have come back, or are not responding to treatment.

Treatments

This trial is divided into 2 parts:

  • Part 1 is to find out the highest safe dose of the combinations of drugs being tested. 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. This continues and the participants are monitored closely 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 highest safe dose of each combination works. People entering this part of the trial all have the same dose.

In this trial, there are also 4 treatment groups in both parts of the trial. These have different treatments alongside the durvalumab and are for different types of lymphoma.

  • In group 1, people with follicular lymphoma or diffuse large B cell lymphoma (DLBCL) have durvalumab with lenalidomide and rituximab.
  • In group 2, people with chronic lymphocytic leukaemia (CLL), small lymphocytic lymphoma or mantle cell lymphoma have durvalumab and ibrutinib.
  • In group 3, people with CLL, small lymphocytic lymphoma, follicular lymphoma or DLBCL have durvalumab, bendamustine and rituximab.
  • In group 4, people with CLL, small lymphocytic lymphoma, follicular lymphoma, DLBCL, mantle cell lymphoma or Hodgkin lymphoma have durvalumab alone.

Your doctor decides which treatment group is best for you based on your individual circumstances and which treatment groups are available to you.

Durvalumab is a type of drug called a monoclonal antibody . This means it is multiple identical copies of a single antibody (a protein that works with your immune system). It blocks signals that cancer cells send that help them hide from the immune system. You have durvalumab intravenously (through a drip into a vein) once a month. You can have it for up to a year.

Ibrutinib is a cell signal blocker and lenalidomide is a drug that changes the way the immune system works. You take both of these by mouth, as capsules.

Rituximab is a monoclonal antibody. You have it intravenously or subcutaneously (as an injection under the skin).

Bendamustine is a chemotherapy drug that you have intravenously.

The dose and treatment schedule varies according to which group you are in. You are given information about the treatments and their schedule.


Who can enter

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

Around 253 people are needed for this trial.

You may be able to enter if:

  • You have been diagnosed with any of the following: B-cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, small lymphocytic lymphoma, Hodgkin lymphoma or chronic lymphocytic leukemia (CLL).
  • If you have CLL or small lymphocytic lymphoma, itis ‘high risk’.
  • Your lymphoma or leukaemia has come back or is not responding to treatment.
  • Your lymphoma is measurable by the tests used in the trial.
  • You are well enough to look after yourself and are up and about more than 50% of your waking hours, even if you are not well enough to work.
  • Your blood and other health test results are satisfactory.
  • You have previously had at least 1 course of treatment for your lymphoma or leukaemia.
  • You are willing and able to have a biopsy.
  • You are over 18.

You will not be able to enter if:

  • You have been treated with a similar drug to durvalumab before, or drugs similar to those in your treatment group.
  • Your lymphoma is in your central nervous system (CNS; brain and spinal cord).
  • You have a condition called myelodysplastic syndrome .
  • You have any type of autoimmune disease .
  • You have ever had an organ transplant or a donor stem cell transplant.
  • You have tested positive for HIV, hepatitis C or hepatitis B.
  • You have ever had TB (tuberculosis) or any condition causing your immune system not to work properly (primary immunodeficiency).
  • You have had another cancer in the last 2 years (or 5 years if you’re in group 1), except for certain localised cancers.

Further information

More information about this trial is available at the UK Clinical Trials Gateway.