REBEL: a phase 2 trial to see how well lenalidomide and rituximab work with or without bendamustine in people with relapsed follicular lymphoma

This trial is testing whether a targeted drug called 'lenalidomide' can be used as part of treatment for follicular lymphoma that has come back after previous treatment. 


Purpose of trial

Follicular lymphoma can be treated successfully but usually relapses (comes back). It is often treated with chemo-immunotherapy (chemotherapy with the antibody treatment rituximab).

The aim of this trial is to see how well a newer targeted drug, lenalidomide, works in combination with rituximab and with or without bendamustine (a chemotherapy drug).


Treatments

Participants are randomised by computer to decide whether or not their treatment includes bendamustine:

  • Group 1: lenalidomide and rituximab
  • Group 2: lenalidomide, rituximab and bendamustine.

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.

You have lenalidomide as tablets. The other drugs are given intravenously (through a drip into a vein) or as a subcutaneous injection (an injection into the layer of fat just beneath the skin).

Each cycle of treatment lasts 4 weeks.

Group 1 has:

  • lenalidomide every day for 3 weeks then 1 week without treatment
  • rituximab on the first day of each cycle.

Group 2 has:

  • rituximab on the first day of each cycle
  • bendamustine on the first 2 days of each cycle
  • lenalidomide on days 3–21 then 1 week without treatment.

You have 3 cycles of treatment before your lymphoma is assessed to see how it is responding. If your lymphoma is the same or reduced, you have another 3 cycles for a total of 6 cycles. If your lymphoma has worsened, you stop treatment and your doctor can discuss other treatment options with you.

After cycle 6, your lymphoma is assessed again. If it is reduced or you are in remission (no evidence of lymphoma), you have rituximab maintenance to give you the best chance of a long-lasting remission. In the maintenance period, you have rituximab once every 3 months for 2 years. If your lymphoma is getting worse, you might need other treatment.


Who can enter

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

Around 80 people are needed in the UK for this trial out of 150 people worldwide.

You may be able to enter if:

  • You have grade 1, 2 or 3a follicular lymphoma that has relapsed.
  • At relapse, your lymphoma is stage 2, 3 or 4.
  • Your lymphoma needs treatment.
  • Your lymphoma is measurable by the tests used in the trial.
  • Your lymphoma cells have a protein called ‘CD20’, which is the target for rituximab.
  • You’ve had up to 5 previous courses of treatment for your lymphoma.
  • You’ve had a maximum of one course of treatment that included bendamustine (up to 6 cycles), this treatment was at least 2 years ago, and your lymphoma responded to treatment with bendamustine.
  • 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 during treatment and for at least 1 year after treatment has finished 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 refractory (doesn’t respond) to rituximab.
  • There are any signs that your lymphoma has transformed (changed) into a faster-growing type. You may be able to enter if your lymphoma previously transformed more than 2 years ago but was successfully treated and there are no signs of transformation when you enrol in the trial.
  • You have ever had an allogeneic stem cell transplant.
  • You have had an autologous stem cell transplant in the last year.
  • You have had lenalidomide or a similar drug before.
  • You have had a bad reaction to lenalidomide, any of its ingredients, or a similar drug before.
  • You are having other anti-cancer treatments or a drug called allopurinol (used to treat excess uric acid, for example gout).
  • You have had another experimental treatment in the last 4 weeks.
  • You have had a yellow fever vaccination in the last 4 weeks.
  • You have HIV or hepatitis C or hepatitis B.
  • You have an active infection.
  • You have certain conditions that are not under control, including autoimmune haemolytic anaemia (AIHA) and idiopathic thrombocytopenic purpura (ITP), hypothyroidism, hyperthyroidism or diabetes.
  • You are being treated with other anti-cancer drugs or immunosuppressive drugs (drugs that lower your immune system).
  • You have any serious health problems that might make it unsafe for you to have the trial treatment, for example heart or lung problems, nerve damage or psychiatric problems.
  • You have had a previous cancer in the last 5 years, unless it was one of a group of localised cancers.