A trial looking at the best treatment for acute myeloid leukaemia (OPTIMISE-FLT3)

Cancer type:

Acute leukaemia

Acute myeloid leukaemia (AML)

Blood cancers

Status:

Open

Phase:

Phase 2/3

This trial is comparing standard treatment Open a glossary item with 2 newer combinations of treatment for acute myeloid leukaemia (AML).

It is for people who have a gene change (mutation Open a glossary item ) called FLT3 in their cancer cells.

Cancer Research UK supports this trial.

More about this trial

Daunorubicin, cytarabine and midostaurin is a cancer drug combination. It is the standard treatment Open a glossary item for acute myeloid leukaemia (AML) with the FLT3 gene change.

Daunorubicin and cytarabine (Ara C) are chemotherapy drugs. Midostaurin is a targeted cancer drug. It stops signals that cancer cells use to divide and grow.

Researchers are looking at ways to improve treatment for AML with the FLT3 gene change. They think that the results from recent clinical trials Open a glossary item could be useful. These included:

adding midostaurin to standard treatment
adding a targeted drug called gemtuzumab ozogamicin to standard treatment
using a combination of 3 chemotherapy drugs called FLAG-Ida

All these drugs are currently treatments for AML. Doctors are looking at combining them into newer combinations to see how they work. So they are doing this trial to find out.

The 2 new combinations of treatment in this trial are:

daunorubicin, cytarabine and midostaurin with gemtuzumab ozogamicin
a combination of 3 chemotherapy drugs called FLAG-Ida with midostaurin and gemtuzumab ozogamicin

In this trial, some people have standard treatment with daunorubicin, cytarabine and midostaurin. And some people have one of the newer combinations of treatment.

The main aims of the trial are to find out:

if either of the newer combinations of treatment works better than standard treatment
more about the side effects

Who can enter

The following bullet points are a summary of the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.

Who can take part

You may be able to join this trial if all of the following apply. You:

have acute myeloid leukaemia (AML)
are well enough to have intensive treatment for AML
have a confirmed FLT3 or TKD gene change (mutation ) in your leukaemia cells. Your doctor will check this. Please note, there is a chance that the test results confirming the FLT3 gene change won’t be available. If you are very unwell and need to start treatment urgently you may be able to join this trial and start treatment. If the FLT3 gene change results show that you don’t have the gene change you would have to withdraw from the trial and stop trial treatment. Your doctor will then talk to you about the best available treatment for your AML.
are willing to use reliable contraception during the trial and for a period after if there is any chance you or your partner could become pregnant
are up and about for at least half the day but might not be able to work (performance status 0, 1 or 2)
are at least 16 years old

Who can’t take part

You cannot join this trial if any of these apply. You:

can’t have the treatments in the trial for any reason. Your doctor will know this.
have already had treatment for AML. You might be able to take part if you are having a drug called hydroxycarbamide to treat high levels of white blood cells in the body.
have chronic myeloid leukaemia that has a lot of immature cells (blasts). This is called blast phase CML and it is similar to acute leukaemia.
have another cancer that needs treatment
have HIV or hepatitis B or C that isn’t well controlled with medication
are pregnant or breastfeeding

Trial design

This phase 2/3 trial is taking place worldwide. The team need to find 390 people to take part. This is 360 people from the UK and 30 people internationally.

It is a randomised trial. A computer puts you into a treatment group. Neither you nor your doctor will be able to decide which group you are in.

There are 3 treatment groups. You have 1 of the following:

daunorubicin, cytarabine and midostaurin (standard treatment)
daunorubicin, cytarabine, midostaurin and gemtuzumab ozogamicin
FLAG-Ida, midostaurin and gemtuzumab ozogamicin

OPTIMISE-FLT3 trial randomisation diagram

You have treatment in stages. The first stage is called induction Open a glossary item . This is to get rid of the leukaemia cells in the bone marrow. The second stage is to stop it coming back. This is called consolidation . The final stage is called maintenance treatment. It reduces the risk of cancer coming back after treatment is finished.

The overall treatment plan for everyone is 4 cycles of treatment Open a glossary item . Cycle one and two are part of your induction treatment. Cycles 3 and 4 are part of your consolidation treatment. This takes about six months in total.

Some people won’t have cycles 3 and 4 of chemotherapy. In particular, some people will need a stem cell transplant or a bone marrow transplant. After cycle 2 or 3, you will stop having chemotherapy if you have a stem cell transplant.

Each cycle has between 19 and 24 days of treatment. This is followed by a few weeks break for you to recover. Your doctor will let you know exactly how long this will be. The first day of each treatment cycle is called day one.

Daunorubicin, cytarabine and midostaurin group (standard treatment)
In the first cycle of treatment you have:

daunorubicin on days 1,3 and 5
cytarabine twice a day for 10 days followed by
midostaurin twice a day for 14 days

In the second cycle of treatment you have:

daunorubicin on days 1, 3 and 5
cytarabine twice a day for 8 days followed by
midostaurin twice a day for 14 days

In the third and fourth cycles of treatment you have cytarabine over 5 days followed by 14 days of midostaurin.

Daunorubicin, cytarabine, midostaurin and gemtuzumab ozogamicin
You have daunorubicin, cytarabine and midostaurin as described above for the first and second cycles of treatment.

In the first cycle of treatment you also have gemtuzumab ozogamicin:

either on days 1 and 4 or
days 4 and 7

In the third and fourth cycles of treatment you have cytarabine over 5 days followed by 14 days of midostaurin.

FLAG-Ida, midostaurin and gemtuzumab ozogamicin
FLAG-Ida includes:

fludarabine chemotherapy
cytarabine chemotherapy
granulocyte colony stimulating factor (G-CSF )
idarubicin chemotherapy

In the first cycle of treatment you have:

fludarabine and cytarabine on days 2 to 6
G-CSF on days 1 to 7
idarubicin on days 4 to 6
gemtuzumab ozogamicin on either day 2 or day 5

This is followed by midostaurin for 14 days.

In the second cycle, you have treatment as described above but you have idarubicin on days 4 to 5.

In the third and fourth cycles you have cytarabine over 5 days. This is followed by 14 days of midostaurin.

Stem cell transplant
You might have a stem cell transplant as part of your overall treatment. This is only if your AML has a high risk of coming back. Your doctor checks your bone marrow samples to work this out. Having a stem cell transplant is a part of standard treatment. You would have this if you needed one even if you weren’t in the trial. Your doctor can tell you more about it.

Having treatment
AML treatment involves lots of different drugs. In this trial you might have them as:

a drip into a vein
an injection under the skin
tablets or capsules that you swallow

Your hospital care team will let you know:

how often you have each drug
how long each drip takes
when to stop taking any treatment

Maintenance treatment
Those who don’t have a stem cell transplant have maintenance treatment Open a glossary item . This involves taking midostaurin twice a day for one year.

Samples for research
You have bone marrow tests and blood samples taken as part of your routine care. Some of the samples are used to plan your treatment. For example, if you need to have a stem cell transplant.

The team will also ask to take extra samples for research when you have your routine bone marrow tests Open a glossary item and blood tests. The team will ask your permission to store these samples for future research. They hope to use them to try and improve treatment for people with AML in the future. You don’t have to agree to this. It won’t affect you taking part in the rest of the trial.

Quality of life
The trial team ask everyone to fill out some questionnaires:

before you start treatment
at set times during treatment
at set times after treatment

The questionnaires ask about side effects and how you’ve been feeling. This is called a quality of life study.

Hospital visits

You see the doctor for a physical examination Open a glossary item and to have some tests before you can take part. These include:

blood tests
a bone marrow test. This is if you haven’t already had one done as part of your routine care.

You might also have some tests before chemotherapy to see how your heart is working. These include:

a heart trace (ECG )
a heart scan (echocardiogram ) or MUGA scan

Your treatment for acute myeloid leukaemia (AML) is intensive, It usually involves spending a lot of time in hospital. Your team will talk to you about how much of your treatment you have on the hospital ward. And how much you will have in the outpatient department. This can differ between hospitals. This is usually the same if you are taking part in the trial or not. Your healthcare team will tell you how often you need to visit hospital during and after your treatment.

You have regular bone marrow tests and blood tests. These are to check how treatment is working and to see how your body is coping with treatment. These are part of your routine care.

Follow up
After treatment has finished, the trial team will monitor you for another 2 years.

Side effects

The trial team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.

The most common side effects of chemotherapy include:

hair loss
a sore mouth
feeling or being sick
problems with how the immune system works
problems with fertility

Some people have had daunorubicin, cytarabine and midostaurin with gemtuzumab ozogamicin in a previous trial. Doctors don’t think that adding gemtuzumab ozogamicin will make the side effects of chemotherapy worse.

Very rarely, gemtuzumab ozogamicin can cause blocked blood vessels in the liver. This is a serious medical problem. Your doctor will check for this and treat it straight away.

You might also have an allergic reaction to gemtuzumab ozogamicin. You have medication to prevent this from happening.

This is the first time people are having FLAG-Ida with midostaurin and gemtuzumab ozogamicin. So there might be side effects we don’t know about yet. The trial team will monitor you closely, especially at the beginning. Your doctor will treat any side effects straight away.

Your doctor will talk to you about all the possible side effects of treatment before you agree to take part.

We have information about the side effects of: