OASIS: a phase 1/2 trial testing the targeted drugs obinutuzumab, ibrutinib and venetoclax (ABT-199) for people with relapsed or refractory mantle cell lymphoma

This trial is testing a combination of three targeted drugs: obinutuzumab, ibrutinib and venetoclax. 


Purpose of trial

The aim of the trial is to see if the combination of three targeted drugs is safe and works well for people with mantle cell lymphoma that has relapsed or was refractory (didn’t respond) to treatment.

Mantle cell lymphoma is a type of non-Hodgkin lymphoma. It is usually high-grade (fast-growing). It usually relapses (comes back) after treatment. 


Treatments

Drugs being tested are:

  • Obinutuzumab, which  is an antibody therapy. It targets CD20, a protein on the lymphoma cells. 
  • Ibrutinib, which is a cell signal blocker. It targets Bruton’s tyrosine kinase (BTK), which is part of a pathway that helps B cells to stay alive and divide (multiply). 
  • Venetoclax (previously called ABT-199), which is a cell signal blocker. It works on a protein called Bcl-2 that helps cancer cells stay alive. Inhibiting Bcl-2 can make cancer cells die.

Ibrutinib is already approved for use in people with relapsed mantle cell lymphoma.

The trial has 2 stages. Stage 1 tested that obinutuzumab and ibrutinib were safe to be used in combination. This stage has already been completed.

Read about the results from part 1 of this trial.

Stage 2 is to find the best dose of venetoclax to use in combination with the doses of obinutuzumab and ibrutinib tested in stage 1. Around 24 people are needed for this stage.

You have treatment in cycles of 4 weeks. You have up to 6 cycles of treatment followed by a maintenance period of up to 18 months where you have treatment less frequently to give you the best chance of staying in remission (no evidence of lymphoma).

Everybody in the trial takes ibrutinib capsules once a day starting from day 2 of cycle 1 and taking them every day throughout the treatment period and maintenance period.

You have obinutuzumab intravenously (into a vein):

  • once a week for the first 3 weeks in cycle 1 then no treatment in week 4
  • once every 4 weeks in cycles 2–6 
  • once every 8 weeks in the maintenance period.

You also have venetoclax by mouth as tablets once a day every day for cycles 2–6 and throughout the maintenance period. Several different doses of venetoclax are being tested to see which works best and has acceptable side effects.


Who can enter

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

You may be able to enter if:

  • You have relapsed or refractory mantle cell lymphoma (confirmed by biopsy) and need treatment.
  • You have previously had a least 1 course of treatment for your lymphoma.
  • Your lymphoma is stage 2, 3 or 4.
  • You are well enough to look after yourself and 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 and your partner are willing to use reliable contraception if there is any chance of you or your partner becoming pregnant. Contraception must continue for at least 18 months after treatment for women for at least 3 months after treatment for men.
  • You are 16–80.

You will not be able to enter if:

  • Your lymphoma is any type other than mantle cell lymphoma.
  • You have lymphoma in your central nervous system (brain and spinal cord).
  • You have significant heart problems or problems with your liver or kidneys.
  • You’ve had a stroke or brain haemorrhage in the last 6 months.
  • You have HIV, active hepatitis C or active hepatitis B.
  • You have an infection that needs to be treated with intravenous antibiotics.
  • You had major surgery in the last 4 weeks.
  • You’ve had a live vaccine in the last 6 months.
  • You are taking certain other drugs that might interfere with the study treatment or you are taking blood thinning medicines like warfarin.
  • You have an allergy to any of the study treatments or related drugs.
  • You’ve had another cancer, except certain localised cancers.
  • You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment.

Further information

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