RAINBOW: a randomised, phase 2/3 trial comparing ibrutinib plus rituximab with standard treatment in people with Waldenström’s macroglobulinaemia

This trial is comparing ibrutinib plus rituximab with standard treatment (dexamethasone, rituximab and cyclophosphamide) in people with Waldenström’s macroglobulinaemia who haven’t been treated before.

Purpose of trial

The aim of this trial is to find out whether chemotherapy-free treatment with ibrutinib plus rituximab is more effective and safer than standard treatment for people with Waldenström’s macroglobulinaemia who haven’t been treated before.


Treatments

Participants are randomly allocated to have one of two treatments:

  • ibrutinib plus rituximab
  • dexamethasone, rituximab and cyclophosphamide (DRC).

You can’t choose which treatment you have and neither can your doctor. You are told which treatment you are having and given information about it.

Ibrutinib is a type of targeted drug called a BTK inhibitor. It blocks signals that encourage lymphoma cells to grow. It is already available to treat Waldenström’s macroglobulinaemia that has come back (relapsed) or not responded (refractory) to initial treatment. You take it as oral capsules once a day for up to 5 years, as long as it is benefiting you.

DRC is standard treatment for people with Waldenström’s macroglobulinaemia who haven’t been treated before. You have up to 6 cycles of treatment.

Rituximab is an antibody therapy that sticks to a protein called CD20 on lymphoma cells. This attracts immune cells, which can kill the lymphoma cells. It is routinely used to treat many types of lymphoma, including Waldenström’s macroglobulinaemia. You have it through a drip into a vein. If you are having it in combination with DRC, you have it on day 1 of each treatment cycle. If you are having it in combination with ibrutinib, you have it on days 1, 8, 15 and 22 of your first cycle of treatment and your fifth cycle of treatment.


Who can enter

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

Around 148 people are needed for this trial.

You may be able to enter if:

  • You have Waldenström’s macroglobulinaemia.
  • You have IgM antibody in your bloodstream that can be measured on blood tests.
  • Your Waldenström’s macroglobulinaemia requires treatment.
  • You have not been treated for Waldenström’s macroglobulinaemia before (except plasma exchange or steroids).
  • You are well enough to take part in the trial.
  • Your blood and other health test results are satisfactory.
  • You are not pregnant.
  • 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 do not have detectable levels of IgM antibody in your bloodstream.
  • You’ve had treatment for Waldenström’s macroglobulinaemia before.
  • You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment.
  • Your lymphoma is in your central nervous system (CNS; brain and spinal cord).
  • You have an infection that needs treatment.
  • You have significant heart disease, kidney disease, liver disease or bowel disease.
  • You have low blood counts caused by blood cells being attacked by your own immune system (autoimmune cytopenia).
  • You have a serious bleeding disorder.
  • You have HIV, hepatitis C or hepatitis B.
  • You’ve had a stroke or bleeding on your brain within the last 6 months.
  • You have had another cancer in the past, except certain localised cancers or cancer that was successfully treated more than 3 years ago with the aim of curing it.
  • You’ve had major surgery in the last 4 weeks.
  • You are on blood-thinning medication (anticoagulants).
  • You are taking certain other drugs that might interfere with the study treatment.
  • You are having treatment as part of another clinical trial.
  • You can’t swallow tablets or capsules.
  • You can’t take, or don’t want to take, antibiotic treatment to stop you getting an infection called pneumocystis pneumonia (PJP).
  • You are pregnant or breastfeeding, or you are planning to become pregnant or make your partner pregnant.
  • You’ve had a bad reaction to antibody therapy in the past.

Further information

More information about this trial is available at clinicaltrials.gov/ct2/show/NCT04061512.