A trial comparing treatment before a stem cell transplant for acute myeloid leukaemia or myelodysplastic syndrome (FIGARO)

Cancer type:

Acute leukaemia

Acute myeloid leukaemia (AML)

Blood cancers

Leukaemia

Myelodysplastic syndrome (MDS)

Status:

Results

Phase:

Phase 2

This trial looked at different combinations of drugs before a stem cell transplant.

It was for people who were having a stem cell transplant with somebody else’s cells. This is an allogeneic transplant Open a glossary item

This trial was open for people to join between 2013 and 2017. The team published the results in 2020.

More about this trial

Doctors often treat acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) with high doses of treatment. It is followed by a transplant using donor stem cells.

Some people have lower dose treatment to reduce the risk of side effects. This is called reduced intensity conditioning or RIC. There is a risk that AML or MDS may come back (relapse) after this lower intensity treatment.

When this trial was done, there was a newer combination of RIC being used. It is called FLAMSA-Bu and includes 6 drugs:

4 chemotherapy drugs called fludarabine, cytarabine, amsacrine and busulphan
2 drugs that damp down the immune system called ATG and mycophenolate mofetil

Researchers thought FLAMSA-Bu might lower the risk of the cancer coming back without causing more side effects. They weren’t sure so they ran this trial to find out more.

In this trial, some people had FLAMSA-Bu before their transplant. And some had 1 of 3 standard combinations of drugs. These were all low intensity treatments.

The main aim of the trial was to find out how well FLAMSA-Bu works compared to other types of low intensity treatment.

Summary of results

The trial team found that FLAMSA-Bu didn’t work better than the standard low intensity treatments. FLAMSA-Bu didn’t increase the length of time people lived or stop the blood cancer coming back.

Trial design
This phase 3 trial took place worldwide. 244 people joined the trial and 216 had treatment. They were put into a group at random Open a glossary item :

108 people had FLAMSA-Bu followed by a stem cell transplant
108 people had standard low intensity treatment followed by a stem cell transplant (the control group )

Diagram 1

People in the control group had one of the following combinations of drugs:

fludarabine, melphalan and alemtuzumab (FMA)
fludarabine, busulphan and alemtuzumab (FBA)
fludarabine, busulphan and ATG (FB-ATG)

Their doctor decided which treatment they should have.

Results
After about 2 years of follow up, the trial team looked at:

the number of people living
whose leukaemia or MDS had come back

They didn’t find a difference in either of these between the 2 groups.

Minimal residual disease (MRD)
After chemotherapy, everyone had a bone marrow test and a blood test. The researchers looked at the results to see if people had any blood cancer cells left in the blood or bone marrow. This is called minimal residual disease Open a glossary item or MRD. They didn’t have samples for everyone.

In the control group, they found:

35 out of 73 (48%) had blood cancer cells – they were MRD positive
38 out of 73 (52%) had no blood cancer cells – they were MRD negative

In the FLAMSA-Bu group they found:

43 out of 72 (60%) had blood cancer cells – they were MRD positive
29 out of 72 (40%) had no blood cancer cells – they were MRD negative

The team found that FLAMSA-Bu didn’t work better for those who were MRD negative. This was compared to those who had standard treatment and were MRD negative.

The team found that the cancer was more likely to come back in those who were MRD positive for both groups.

Number of donor cells
After the transplant, the trial team checked the number of donor cells in the bone marrow and blood. To do this they did a blood and bone marrow test at 3 months.

They looked at who had:

all donor cells (100% donor cells)
a mix of donor cells and their own cells

The results were similar for both treatment groups. They found that those in both groups who had all donor cells at this time point had a lower chance of the blood cancer coming back.

The team noted that having all donor cells at 3 months was important. People who were MRD positive before their transplant did as well as those who were MRD negative if they had all donor cells in their blood and bone marrow samples.

Side effects
The trial team looked at the more severe side effects of treatment. These side effects happened in:

89 people who had FLAMSA-Bu
66 people in the control group

The most common severe side effects for both groups were:

a drop in blood cells causing an increased risk of infection, bruising and bleeding, tiredness, and shortness of breath
feeling or being sick
diarrhoea
infections

Conclusion
The trial team concluded that FLAMSA-Bu didn’t work better than standard treatment for people having a stem cell transplant. And it didn’t work better for those who were MRD negative compared to those who were MRD positive.

Even so, all trial results help doctors and researchers understand more about different cancers and the best way to treat them.

The trial team suggest more work is done looking at different combinations of treatment. They hope to find out whether they can use MRD results to decide which treatment to give people.

Where this information comes from
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.