A trial looking at treatment for acute myeloid leukaemia (AML17)

Cancer type:

Acute leukaemia

Acute myeloid leukaemia (AML)

Blood cancers

Leukaemia

Myelodysplastic syndrome (MDS)

Status:

Results

Phase:

Phase 3

This trial was looking at different treatments for acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) that had a high risk of coming back.

Cancer Research UK supported this trial.

More about this trial

AML17 was a complicated trial testing a lot of different treatments. The main aim was to find out which treatment:

was best at stopping AML and MDS coming back
caused the fewest side effects

Myelodysplastic syndromes (MDS) are blood disorders. High risk MDS means there is more chance it might develop into AML over time. MDS is classed as high risk if more than 10% of your bone marrow is made up of immature cells called blasts. High risk MDS is treated in a similar way to AML.

Chemotherapy is the usual first treatment for AML and high risk MDS. The aim is to get rid of leukaemia cells (getting it into remission). This first treatment is called induction therapy.

In this trial, researchers looked at 2 different types of induction chemotherapy. They looked at adding a targeted cancer drug called gemtuzumab ozogamicin (mylotarg or GO) to the first induction treatment in some people. At a later point in the trial, the researchers also looked at 2 different doses of daunorubicin (alongside Ara C) as part of the first induction treatment.

For the 2nd course of induction chemotherapy, the researchers put people into different treatment groups depending on:

the risk of the leukaemia coming back
whether they had certain gene changes (mutations ) in the leukaemia cells

The trial also looked at a number of different targeted cancer drugs alongside this chemotherapy. These included:

gemtuzumab ozogamicin for people with an abnormal chromosome called ‘core binding factor’
lestaurtinib (CEP-701) for people with a change on a gene called FLT3
everolimus – although the trial team found this didn’t work so this part of the trial closed early
pacritinib for people whose leukaemia came back and who had a certain gene change in the leukaemia cells

If the leukaemia goes away completely, this is called complete remission. To stop AML coming back, you then have more chemotherapy. This is called consolidation chemotherapy. In this trial, they looked at consolidation treatment for people who didn’t have a high risk of the leukaemia coming back and those who did have a high risk.

For people with a lower risk of their leukaemia coming back it compared the following:

1 cycle of cytarabine
2 cycles of cytarabine

Some people with high risk leukaemia had a complete remission and some didn’t. In this group of people they compared:

standard FLAG-Ida – this includes the drugs fludarabine, cytarabine, G-CSF and idarubicin
daunorubicin and clofarabine

Some then went on to have a stem cell transplant.

In summary, the researchers tried to answer a number of questions about AML treatment. These were to find out:

the best dose of mylotarg to have alongside induction chemotherapy
if it was useful to increase the dose of daunorubicin for the first course of induction treatment
whether lestaurtinib (CEP-701) works for people with a FLT3 gene change
if 1 or 2 courses of consolidation chemotherapy improved treatment for AML
more about doing extra monitoring

Please note - there is another part of the AML17 trial that looked at a type of adult acute myeloid leukaemia (AML) called APL. There is summary of the results for the APL trial on our trials database.

Summary of results

The researchers have produced results from the parts of the trial that looked at:

mylotarg and standard induction treatment
daunorubicin and cytarabine induction treatment
extra monitoring to predict relapse
induction treatment with lestaurtinib (CEP-701)

The trial focused on people under the age of 60. But some people over 60, suitable to have intensive treatment took part.

Results of mylotarg alongside induction chemotherapy
We know from research that gemtuzumab ozogamicin (also called Mylotarg or GO) is a useful treatment for AML. But researchers weren’t sure if having a higher dose could improve treatment.

In this part of the trial, they compared 2 different doses of mylotarg alongside induction chemotherapy. These results were published in 2016. They found that having a higher dose didn’t improve treatment and the side effects were worse.

788 people joined this part of the trial between 2009 and 2011. They were put into 1 of 2 treatment groups at random.

393 had the usual dose of mylotarg and standard induction chemotherapy.
395 had higher dose mylotarg and standard induction chemotherapy.

The trial team looked at:

how well the treatment worked
how long before the leukaemia came back
how long people lived for after treatment

At 4 years, the trial team found no difference in any of these.

Side effects such as raised levels of liver enzymes and low platelets Open a glossary item were much worse in the people who had the higher dose of mylotarg.

The researchers concluded there was no benefit to having a higher dose of mylotarg in combination with induction chemotherapy. They say the lower dose was adequate but the best dose is still unclear. This is being looked at in other ongoing AML trials such as the AML19 trial.

Results of induction treatment with daunorubicin
In this part of the trial, researchers looked at increasing the dose of daunorubicin. They wanted to see which dose worked best.

1,206 people who hadn’t had treatment for AML or high risk MDS took part. They joined the trial between 2011 and 2013. The average age was 53. They were put into 1 of 2 groups at random.

602 had the usual dose of daunorubicin and cytarabine
604 had a higher dose daunorubicin and cytarabine

The average length of time people were followed up was 14.8 months. They found there was no difference between having the 2 different doses of daunorubicin in:

the number of people alive
the number whose leukaemia had come back
any of the AML sub groups (these groups were based on people’s age, white cell count, stage of leukaemia and any differences in how the leukaemia had responded to the 1^st treatment)

People who had the higher dose had more sickness and diarrhoea.

The trial team found that for most people, there was no overall benefit to having the higher dose of daunorubicin. The exception to this was those people found to have a change in a gene called FLT3. The researchers found that a higher dose might be useful in this group of people.

Results of induction treatment with lestaurtinib (CEP-701)
1 in 3 people with AML have change in a gene called FLT3. Having this change can increase the risk of the leukaemia coming back. Researchers are trying to find out how best to treat these people. They are looking at a type of cancer growth blocker called lestaurtinib (also known as CEP-701).

In this trial, 325 people had the FLT3 gene change. For their second course of induction chemotherapy, they were put into 1 of 2 treatment groups at random:

212 people had chemotherapy and lestaurtinib
113 people had chemotherapy and a dummy drug

These results were combined with the results of another trial called AML15. Some people in the AML15 trial also had treatment with or without lestaurtinib. So in total, researchers looked at the results of 500 people. They looked at:

whether the leukaemia came back and how long this took
how long people lived for after treatment

At 5 years, the trial team couldn’t find any evidence that there was a difference between the 2 treatment groups in either of these.

The trial team noticed slightly better results in those people who had lestaurtinib and:

treatment with mylotarg as part of the first induction chemotherapy
antifungal drugs to prevent fungal infection

Fewer people had leukaemia that came back (relapsed). And there was a small increase in the time that people lived following relapse. The different results in this group of people were small and not significant.

Side effects, such as diarrhoea and feeling sick, were slightly higher in the group who had lestaurtinib. And more people in this group needed treatment for infection compared to those who did not have lestaurtinib.

The researchers concluded that people did not benefit from having lestaurtinib in this trial, but we need more research into this drug.

Results of monitoring
When this trial was done, the standard way to predict if leukaemia might come back (relapse) was to look at a number of markers in blood and bone marrow samples before treatment began. This helped doctors to decide who had a high or low risk of relapse at the start of treatment. It also guided them as to when they thought someone might need to have a stem cell transplant.

But they wanted to find better ways of predicting relapse in people who weren’t in either of the high or low risk groups, but had an average chance of their leukaemia coming back. They hoped a blood test to check for a certain marker could help.

To begin with, researchers tested blood and bone marrow samples to check for a gene change (marker) in leukaemia cells called NPM1. This was an optional study. They found 346 people had the marker.

After the 2nd cycle of chemotherapy, people had another bone marrow and blood test to look for the marker. Finding the marker meant there were small numbers of leukaemia cells left after treatment. This is called minimal residual disease or MRD.

The researchers found that the blood test could detect if someone was in ‘molecular remission’. This meant there were no signs of the changed genes that show up in leukaemia cells in their blood. They also found that it could predict relapse. The results showed that after the 2^nd cycle of chemotherapy:

just over 8 out of 10 people (82%) who had the markers (were MRD positive) had relapsed at 3 years
3 out of 10 people (30%) who didn’t have the marker (were MRD negative) went on to relapse within that time

The trial team concluded the blood test is very useful and is much better than standard ways of predicting relapse. They say the test can predict who is at risk of their AML returning in the future. This helps to guide doctors on what treatment to have and specifically when people should have a stem cell transplant.

More research is taking place to discover the best stage in treatment for people to have a transplant in the AML19 trial.

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.