A trial looking at adding rituximab and mitoxantrone to fludarabine and cyclophosphamide to treat chronic lymphocytic leukaemia (ARCTIC)

This trial is looking at adding rituximab and mitoxantrone to fludarabine and cyclophosphamide to treat people with chronic lymphocytic leukaemia.

Doctors often use chemotherapy to treat chronic lymphocytic leukaemia (CLL). One of the combinations of chemotherapy they use is fludarabine and cyclophosphamide.

We know from research that adding rituximab or mitoxantrone to fludarabine and cyclophosphamide may be better for treating CLL than fludarabine and cyclophosphamide alone.

Rituximab is a biological therapy called a monoclonal antibody. Rituximab works by attaching itself to a protein on the leukaemia cell. This makes it easier for the immune system to find the leukaemia cells and kill them. We know from research that a smaller dose of rituximab may be as good as or better than the standard dose used currently for CLL.

Mitoxantrone is a chemotherapy drug. It works by blocking an enzyme that cancer cells need to divide. Without this enzyme cancer cells are not able to divide and grow.

The researchers think that a low dose of rituximab with mitoxantrone added to fludarabine and cyclophosphamide may be just as good for treating CLL as adding the standard dose of rituximab to fludarabine and cyclophosphamide.

The aim of this trial is to compare the chemotherapy combinations of

Cyclophosphamide, fludarabine and rituximab
Cyclophosphamide, fludarabine, mitoxantrone and low dose rituximab

Recruitment

Start 01/12/2009

End 30/11/2012

Phase

Phase 2

Who can enter

You can enter this trial if

You have B cell chronic lymphocytic leukaemia (B cell CLL)
You have fewer than 3 groups of enlarged lymph glands and a high white blood cell count (stage A) that is getting worse OR more than 3 groups of enlarged lymph nodes (or an enlarged spleen) with a high white blood cell count (stage B,C)
You need to have treatment for your B cell CLL
You are well enough to be up and about for half the day (performance status 0,1 or 2)
You have satisfactory blood tests results
Your kidneys work well enough (your doctor will test for this)
You are willing to use reliable contraception if there is a chance that you or your partner could become pregnant
You are at least 18 years old

You cannot enter this trial if

You have chronic lymphocytic leukaemia that is in your spinal cord or brain (central nervous system)
You have already had treatment for your chronic lymphocytic leukaemia
Your red blood cells are being destroyed, unless you are taking a small dose of steroids to control this (your doctor can advise about this)
You are allergic to any of the drugs in this trial
You have an infection
You have heart failure or angina that is not controlled by medication
You are known to be HIV, hepatitis B or hepatitis C positive
You have another type of cancer except basal cell carcinoma
You have another serious medical condition that could affect you taking part in this trial

Trial design

This is a phase 2 trial. It will recruit about 206 people in the UK. It is a randomised trial. The people taking part are put into 1 of 2 treatment groups. Neither you nor your doctor can choose which group you are in.

The people in group1 will have fludarabine, cyclophosphamide and standard dose rituximab.

The people in group 2 will have fludarabine, cyclophosphamide, low dose rituximab and mitoxantrone.

Fludarabine and cyclophosphamide are chemotherapy tablets you take at home. You take them once a day for 5 days, then have 23 days of no fludarabine or cyclophosphamide.

You have rituximab and mitoxantrone through a drip in to a vein (intravenously). You have them once every 28 days.

Each 28 days is a cycle of treatment. After 3 cycles of treatment you see the doctor to see if the treatment is helping. If it is, you will have 3 more cycles of treatment.

You fill in a questionnaire before you start treatment, after 3 cycles of treatment, at the end of treatment and then every 3 months to 2 years. It will ask how you are feeling and what activities you can do.

If you agree to take part in this trial the researchers may ask your permission to take some extra blood samples, a saliva sample, and some samples from your bone marrow test. These samples will be stored safely and may be used in the future for research purposes only. Studying these samples may help researchers learn more about leukaemia.

Hospital visits

You will see the doctor and have some tests before you take part in this trial. These tests include

Physical examination
Blood tests
CT scan
Heart trace (ECG)
Bone marrow test

After 3 cycles of treatment, and at the end of treatment, you see the doctor and have a physical examination and blood tests.

You see the doctor 3 months after treatment and have a physical examination, blood tests and bone marrow test.

You then see the doctor every 6 months up to 2 years, then once a year. At these visits you will have a physical examination and blood tests. You may also need to have a CT scan and your doctor will discuss this with you.