A trial looking at treatment for people with newly diagnosed chronic lymphocytic leukaemia (ADMIRE)

Please note this trial is no longer recruiting patients.

This trial is looking at standard chemotherapy and rituximab with or without mitoxantrone for people with newly diagnosed chronic lymphocytic leukaemia (CLL).

Doctors usually treat CLL with 2 chemotherapy drugs called fludarabine and cyclophosphamide. Sometimes they give chemotherapy in combination with a newer type of biological therapy called rituximab. Doctors call this combination FCR.

Earlier trials showed that adding a chemotherapy drug called mitoxantrone to FCR is a useful treatment for CLL. Doctors call this combination FCM-R. The doctors in this trial think that this combination will help to lower the number of leukaemia cells that can be left behind after treatment. Doctors call these remaining cancer cells ‘minimum residual disease’ or MRD. An undetectable MRD level means the leukaemia is less likely to come back.

The aims of this trial are to find out

If FCM-R is better than FCR for people with newly diagnosed CLL
More about the side effects

Recruitment

Start 01/06/2009

End 30/03/2012

Phase

Phase 2

Who can enter

You can enter this trial if you

Have B cell chronic lymphocytic leukaemia (B cell CLL) including a type called small lymphocytic (SLL) and you have not had treatment
Have a high number of lymphocytes, low numbers of platelets and a low red blood cell count – you can check this with your doctor
Have enlarged lymph nodes, liver or spleen – you can check this with your doctor
Have stage B or C CLL or you have stage A that has worsened and you need treatment
Have at least one of the following symptoms– significant weight loss, tiredness (fatigue) that makes it difficult to go about your usual daily activities, high fevers for at least 2 weeks with no signs of an infection or night sweats for more than 2 months with no signs of an infection
Are well enough to take part (performance status 0, 1 or 2)
Are willing to use reliable contraception if there is any chance that you or your partner could become pregnant
Have satisfactory blood and urine test results
Are at least 18 years old

You cannot enter this trial if you

Have already had treatment for B cell CLL
Have B cell CLL that has spread to your brain or spinal cord (central nervous system)
Have ‘mantle cell’ lymphoma
Have a very low number of neutrophils and platelets or you have regular blood transfusions unless this is because your CLL is in the bone marrow
Have significant heart problems or angina that is not controlled with medication
Have significant bleeding problems
Have kidney problems
Have an infection that won’t get better
Have had a sudden, severe allergic reaction (‘anaphylactic shock’) after antibody treatment
Have had any other cancer apart from basal cell skin cancer
Are pregnant or breastfeeding
Have Hepatitis B, Hepatitis C or HIV

Trial design

218 people will take part in this phase 2 trial. It is a randomised trial. The people taking part will be put into 2 different groups by computer. Neither you nor your doctor can decide which group you are in.

If you are in group 1 you will have fludarabine, cyclophosphamide and rituximab (FCR). If you are in group 2 you will have fludarabine, cyclophosphamide, rituximab and mitoxantrone (FCM-R).

Each 4 week period is one cycle of treatment. You take fludarabine and cyclophosphamide tablets everyday for the first 5 days of each treatment cycle. You have rituximab as a drip into a vein on the first day of each treatment cycle. If you are in group 2 you also have mitoxantrone as a drip into a vein on the first day of each treatment cycle. Everyone will have up to 6 cycles of treatment. The treatment will take up to 6 months in total.

You will have some tests after the third cycle of treatment. If the tests show treatment is working well, you will continue to have 3 more treatment cycles. If the treatment is not helping you the doctor will probably decide to stop treatment and will discuss further treatment options with you.

Hospital visits

You will see the doctors and have some tests before you start treatment. The tests include

Physical examination
Heart trace (ECG)
Bone marrow test
CT scan of your chest, stomach and pelvic area
Chest X-ray
Blood tests
Urine tests

3 months after you finish treatment you will have some of these tests again, to see how well the treatment has worked. You will also see the trial doctor every 6 months for up to 2 years and then yearly after that.

Side effects

The most common side effects of chemotherapy include

A drop in blood cells causing an increased risk of infection, shortness of breath, tiredness and bleeding or bruising problems
Tiredness (fatigue)
Hair loss
Diarrhoea

Rituximab does not seem to cause serious side effects. But when you first have rituximab you may have side effects such as