ACE-LY-110: a phase 1/2 trial testing the combination of newer drugs acalabrutinib and vistusertib for people with diffuse large B-cell lymphoma (DLBCL)

This trial is testing new treatments for people with diffuse large B-cell lymphoma (DLBCL) who have already had treatment but their lymphoma is not considered curable with current treatments.


Purpose of trial

The aim of this trial is to find out if the combination of acalabrutinib and vistusertib can be used to treat people with diffuse large B-cell lymphoma (DLBCL) that has come back (relapsed) or didn’t respond (was refractory) to previous treatment.

People with a low-grade (slow-growing) type of lymphoma that has transformed (changed) to DLBCL can also enter this trial.

The trial is in 2 parts.

  • The first part of the trial aims to find the best dose of vistusertib to use in combination with acalabrutinib.
  • The second part tests the safety and effectiveness of the dose selected in the first part.

Treatments

Acalabrutinib is a cell signal blocker that works in a similar way to ibrutinib. It is more selective than ibrutinib in its target, so it is expected that it will have a greater effect on cancer cells and cause fewer side effects.

Vistusertib is a targeted drug that works by blocking the action of a protein called mTOR. This protein is part of a signalling pathway that controls how cells grow and divide. In lymphoma, abnormal cells grow and divide in an uncontrolled way. Blocking the growth and division of these abnormal cells with vistusertib could cause them to die or control their growth and division.

Everyone in this trial has acalabrutinib and vistusertib. Both drugs are taken orally (by mouth) as capsules.

Everyone takes acalabrutinib every day.

The dosing schedule of vistusertib depends on what group you are in. You either take vistusertib every day or for 5 of every 7 days.

In both groups, each cycle of treatment is 28 days and you can have up to 12 cycles as long as the trial treatment is controlling your lymphoma and you do not develop troublesome side effects.

If you are still benefitting from the treatment after 12 cycles, you may be able to enter an additional study so that you can continue to receive it. The trial team can discuss with you whether you want to enter the new study at that time.


Who can enter

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

Around 59 people are needed for this trial.

You may be able to enter if

  • You have DLBCL including a low-grade lymphoma, for example chronic lymphocytic leukaemia (CLL) or follicular lymphoma, that has transformed into DLBCL.
  • Your diagnosis has been confirmed by biopsy.
  • You have had previous treatment for your lymphoma including at least one previous course of chemo-immunotherapy (chemotherapy with antibody therapy).
  • Your lymphoma is not considered to be curable with available treatments.
  • You are well enough to look after yourself and are up and about at least 50% of the day even if you are unable to work.
  • Your lymphoma is measurable by the tests used in the trial.
  • You are 18 or over.

You will not be able to enter if

  • You have primary mediastinal large B-cell lymphoma (PMBL).
  • You have an active infection or have had intravenous (into a vein) treatment for an infection in the last 2 weeks.
  • You have serious lung or heart problems or uncontrolled high blood pressure.
  • You have an unusual susceptibility to bleeding (for example you have haemophilia or von Willebrand disease).
  • You have digestive problems that might mean the trial treatment is not absorbed properly.
  • Your lymphoma is affecting your central nervous system (brain and spinal cord).
  • You have serious liver or kidney problems.
  • You have any other problems that your doctor thinks make it unsafe for you to have the study treatment.

Further information

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