Purpose of trial
The aim of the trial is to investigate a new drug called M7538 and find out: the maximum dose that can be given without causing serious side effects; more about the side effects; how well it works for B-cell non-Hodgkin lymphomas that have come back (relapsed), or are not responding to treatment (refractory).
There are 2 parts to the trial. Part 1 is recruiting people with diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia, small lymphocytic lymphoma, mantle cell lymphoma or Waldenström’s macroglobulinemia. Part 2 is recruiting people with DLBCL of the ABC subtype and mantle cell lymphoma with confirmed cyclin D1 overexpresssion or t(11;14) translocation). Your doctor can advise if this applies to you.
Different doses of M7583 are being tested in this trial:
- Part 1 is to find out the highest safe dose of M7583. 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 will be used in part 2 of the trial.
- Part 2 is to test how well the highest safe dose of M7583 works. People entering this part of the trial all have the same dose of M7583.
M7583 is a type of cell signal blocker called a Bruton’s tyrosine kinase (BTK) inhibitor. It targets and blocks a protein that helps B cells to stay alive and divide. Blocking BTK can help to stop lymphoma from growing and can make the lymphoma cells die.
M7583 is a drug that you take every day. You have it by mouth (orally) as capsules once a day. You continue to take it for as long as it is helping you.
Who can enter
Your consultant can give you advice on whether this trial might be suitable for you.
Around 60 people are needed for this trial.
You may be able to enter if:
- You have B-cell non-Hodgkin lymphoma (diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia, small lymphocytic lymphoma, mantle cell lymphoma or Waldenström’s macroglobulinemia) that has come back or is no longer responding to treatment.
- You have previously had 1–3 courses of treatment for your lymphoma and your lymphoma has got worse since your most recent 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 test results are satisfactory.
- You agree to have biopsies of your lymphoma before and during treatment or bone marrow biopsies if your lymphoma is in your bone marrow.
- 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 will not be able to enter if:
- Your lymphoma is in your central nervous system (CNS; brain and spinal cord).
- You have prolymphocytic leukaemia or Richter’s transformation (CLL has changed into a more aggressive lymphoma).
- Your doctor thinks you still have significant side effects from your previous treatment.
- You have been treated with a similar drug before (eg ibrutinib).
- You’ve had surgery in the last 3 weeks.
- You have had an allogeneic stem cell transplant or autologous stem cell transplant in the last 6 months.
- You have had anticancer treatment in the last 4 weeks or the chemotherapy drugs nitrosurea (BCNU or carmustine) or mitomycin C in the last 6 weeks.
- You have had another experimental drug in the last 4 weeks.
- You’ve had more than 3 courses of anticancer treatment.
- You are taking certain other drugs that might interfere with the study treatment, eg warfarin. Ask the trial doctor for details.
- You have recently taken drugs, herbal supplements or food that affect proteins in a family called CYP3A. Ask the trial doctor for details.
- You have significant heart problems.
- You have high blood pressure that is not well controlled.
- You are pregnant or breastfeeding.
More information about this trial is available at clinicaltrials.gov.