A trial looking at mitoxantrone and low dose rituximab with chemotherapy for chronic lymphocytic leukaemia (ARCTIC)

Cancer type:

Blood cancers

Chronic leukaemia

Chronic lymphocytic leukaemia (CLL)

Leukaemia

Status:

Results

Phase:

Phase 2

This trial was for people with chronic lymphocytic leukaemia (CLL). It was for people who had not yet had treatment for their disease.

More about this trial

Chemotherapy and a targeted drug is the usual treatment for chronic lymphocytic leukaemia (CLL). For example, you might have all of the following:

rituximab (a targeted drug)
fludarabine and cyclophosphamide (chemotherapy drugs)

You only usually have this combination if you are fairly fit and well.

Earlier trials have shown that adding mitoxantrone might improve treatment for CLL. Mitoxantrone is a type of chemotherapy. It works by blocking an enzyme that cancer cells need to divide. Without this enzyme cancer cells are not able to divide and grow.

Doctors also thought that a low dose of rituximab might work just as well as a standard dose of this drug. Rituximab is a monoclonal antibody, it attaches itself to a protein on the leukaemia cell. This makes it easier for the immune system to find the leukaemia cells and kill them.

In this trial, people had one of the following treatments:

standard dose rituximab with fludarabine and cyclophosphamide (FCR)
low dose rituximab with mitoxantrone, fludarabine and cyclophosphamide (FCM-miniR)

The aim of the trial was to find out if using a low dose of rituximab and adding mitoxantrone worked as well as standard FCR treatment. The researchers also wanted to compare the side effects of each treatment.

Summary of results

This was a phase 2 trial. It recruited 206 people in the UK. It was randomised trial, so the people taking part were put into 1 of 2 treatment groups by a computer.

Half of people had fludarabine, cyclophosphamide and standard dose rituximab (FCR).
Half of people had fludarabine, cyclophosphamide, low dose rituximab and mitoxantrone (FCM-miniR).

During the trial, the researchers looked at how well the treatment was working. They found that standard treatment with FCR was working better than treatment with mitoxantrone and low dose rituximab (FCM-miniR). Because of these results the trial closed early.

Response to treatment
Those who were still having FCM-miniR at the time the trial closed were able to change to FCR if they wanted to. Twenty one people chose to cross over from FCM-miniR to complete their treatment with FCR. These people weren’t included in the final results.

Three months after treatment had finished the researchers carried out a final analysis of the results. They looked at how many people had no sign of CLL (a complete response). This included:

68 out of the 100 people (68%) who had FCR
39 out of the 79 people (49%) who had FCM-miniR

The researchers concluded that this meant that FCR-miniR is not as good as FCR.

Adverse events
The researchers compared the number of adverse events of people in the 2 groups. An adverse event means any medical event that happens to people while taking part in a trial. This includes any side effect thought to be due to the treatment in the trial. And any medical event that might not be due to treatment.

The researchers recorded how many people had at least one serious adverse event. For example:

an infection that needed immediate hospital treatment
development of squamous cell skin cancer
diarrhoea that needed hospital treatment as an in patient

Those who had at least one serious adverse event included:

46 people in the FCM-miniR group
49 people in the FCR group

A higher proportion of people in the FCM-miniR group compared with the FCR group were admitted to hospital for a serious adverse event during the trial.

Survival
The trial team also looked at:

whose leukaemia came back (relapsed) or started to grow again and when this happened (progression free survival)
how long people lived for (overall survival)

The researchers specifically recorded these figures when people had on average been followed up for about 3 years. They found no significant difference in progression free survival or overall survival between the 2 groups. The trial team are continuing to collect information about survival.

The researchers concluded that standard dose rituximab with fludarabine and cyclophosphamide remains the best treatment for people with CLL. They also found that adding mitoxantrone increased the side effects that people had.

They recommended that treatment with low dose rituximab, mitoxantrone, fludarabine and cyclophosphamide should not move into phase 3 clinical trials.

We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.