A trial of ibrutinib and rituximab for post-transplant lymphoproliferative disorder (TIDaL)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Blood cancers

Lymphoma

Secondary cancers

Status:

Closed

Phase:

Phase 2

This trial is looking at the combination of ibrutinib and rituximab for people who develop a condition called post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder can develop after a:

stem cell transplant, a treatment used for some types of cancer
an organ transplant , such the heart, lung or liver

More about this trial

After a transplant, if your immune system isn’t strong enough a type of white blood cell called B cells might grow out of control. This is post-transplant lymphoproliferative disorder (PTLD).

The initial treatment for PTLD is a targeted drug called rituximab. This works very well for about 25 out of every 100 people (25%).

For people where rituximab by itself doesn’t work well chemotherapy is added. The standard treatment for these people is a combination called R-CHOP:

• rituximab (R)

• cyclophosphamide (C)

• doxorubicin (H)

• vincristine (O)

• prednisolone (P)

R-CHOP does work. But there is a high risk of:

getting an infection
damage to the transplant
side effects

We know from research that ibrutinib by itself or in combination with rituximab works for a type of cancer called lymphoma Open a glossary item

In this trial everyone has ibrutinib and rituximab as their first treatment. After a number of weeks of treatment, the researchers look at how well this has worked.

If it has worked well, you continue to have ibrutinib and rituximab. If it hasn’t worked so well, you have ibrutinib and R-CHOP.

The aims of this trial are to find out:

how well ibrutinib and rituximab work as initial treatment for PTLD
if adding ibrutinib to R-CHOP works better
about the side effects of these treatments

Who can enter

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.

Who can take part

You may be able to join this trial if all of the following apply:

you have post-transplant lymphoproliferative disorder (PTLD) that has the CD20 protein
you haven’t had treatment for PTLD
you have an area of PTLD that can be measured and is greater than 2cm and, or your bone marrow has been affected by PTLD
you have had a donor stem cell transplant and the PTLD developed more than 6 months afterwards or you have PTLD because you have had a transplant of your heart, lung, liver, kidney, pancreas or small intestine
you have satisfactory blood test results
your heart works well enough, you have a test for this
you are up and about, can look after yourself but can’t work (performance status 0, 1 or 2)
you are willing to use reliable contraception during the trial and for up to a year after if you or your partner could become pregnant
you are at least 16 years old

Who can’t take part

You cannot join this trial if any of these apply. You:

have PTLD that has come back (relapsed) or continued to grow during treatment (refractory)
have had all the PTLD removed by surgery
have radiotherapy to any areas of PTLD that were left after surgery
have developed PTLD within 6 months of having a donor stem cell transplant
have PTLD that is caused by a type of white blood cell called T cells
have already had rituximab or chemotherapy treatment for your PTLD
need to continue with a medication, including herbal medicines, that could affect how the treatments in this trial works
have had medication that thins your blood such as warfarin or a vitamin K blocker, within 1 week of being registered for this trial
have a severe problem with one or more of your body organs that isn’t due to PTLD
have HIV
have active hepatitis B or any other serious active infection that the trial team think could affect you taking part in the trial
have an allergy to any of the drugs used in this trial or there is another reason you can’t have them
are pregnant or breastfeeding

Trial design

This is a phase 2 trial. The team need up to 60 people to join the trial.

There are 2 stages of treatment in this trial.

Stage 1
Everyone has ibrutinib and rituximab for up to 7 weeks.

You then have a CT scan to see how well the treatment is working.

Stage 2
What treatment you have in this stage depends on how well the treatment in stage 1 worked for you.

If treatment worked well, you continue with ibrutinib and rituximab.

If it worked a little bit or didn’t work you have ibrutinib and R-CHOP.

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Ibrutinib is a capsule. You take 1 capsule a day at the same time at least 30 minutes before food or 2 hours after food.

You have rituximab as a drip into a vein. You have it once a week for the first 4 weeks and then once every 3 weeks.

R-CHOP is the standard treatment for PTLD. It includes the drugs:

rituximab
doxorubicin
cyclophosphamide
vincristine
prednisolone

You have rituximab, doxorubicin, cyclophosphamide and vincristine as a drip into a vein. You have them once every 3 weeks.

Prednisolone is a tablet. You take it once a day for 5 days.

You can have up to 5 months of treatment in total.

You have a diary to write down when you have your ibrutinib. You need to bring this to your hospital appointments for your doctor to see.

While having treatment there are certain foods, drinks and medications you should avoid. These include:

grapefruit and its juice
Seville oranges and its juice
marmalade
St John’s wort
vitamin E
certain antibiotics

Your doctor will talk to you about this and give a full list of what to avoid.

Hospital visits

You see your doctor to have tests before taking part in the trial. These tests include:

a physical examination
blood tests
heart trace (ECG )
heart scan (ECHO or MUGA )
breathing test (lung function tests )
CT scan
PET scan
MRI scan
bone marrow test
a tissue sample (biopsy) of the PTLD unless one was taken in the past 6 months and the team are able to obtain a piece of it

For stage 1 treatment

You see the doctor every week for a month for:

a physical examination
blood tests

At 7 weeks you see the doctor for:

a physical examination
blood tests
CT scan
breathing test
heart scan, if needed

For stage 2 treatment

You see the doctor every 3 weeks for:

a physical examination
blood tests

At 6 weeks you have more breathing tests. You might have another heart scan if your doctor thinks it is needed.

At the end of treatment, you see the doctor for:

a physical examination
blood tests
heart trace (ECG)
heart scan (ECHO or MUGA), if needed
breathing test (lung function tests)
CT scan
PET scan
MRI scan
bone marrow test

After treatment you see the doctor every 4 months for 2 years to see how you are and for blood tests. You have a CT scan after 1 year.

Side effects

Your doctor and nurse will monitor you closely for any side effects. Let your doctor or nurse know as soon as possible if:

you have severe side effects
your side effects aren’t getting any better
your side effects are getting worse
you notice anything unusual or anything that has changed

The most common side effects of ibrutinib include:

diarrhoea or constipation
muscle and bone pain
feeling or being sick
a drop in blood cells causing an increased risk of infection, bruising and bleeding
rash and, or skin infection
lung infection (pneumonia)
joint aches
increase risk of getting a cold
high temperature (fever)
muscle twitch, shudder or seizure (muscle spasms)
mouth sores
headache
high blood pressure
sinus infection (sinusitis)