A trial looking at different treatments for acute myeloid leukaemia and high risk myelodysplastic syndrome (AML 19)

Cancer type:

Acute leukaemia
Acute myeloid leukaemia (AML)
Blood cancers
Leukaemia
Myelodysplastic syndrome (MDS)

Status:

Open

Phase:

Phase 3

This trial is looking at different treatments for acute myeloid leukaemia (AML) and high risk myelodysplastic syndrome (MDS). It is for people who are fit enough to have intensive treatment. This trial is supported by Cancer Research UK.

More about this trial

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. 

Doctors usually treat AML with chemotherapy and other drugs to get rid of the leukaemia cells (getting it into remission Open a glossary item). This first part of treatment is called induction therapy.

If induction treatment is successful, you usually have treatment to lower the chances of the leukaemia coming back. This is called consolidation treatment. Some people may then have a transplant using the stem cells or bone marrow of a donor.

This trial is trying to answer a number of questions about the treatment of AML and high risk MDS. These include trying to find out 

  • Which combination of chemotherapy works best in induction treatment 
  • If 1 or 2 courses of consolidation chemotherapy improve treatment for AML 
  • Whether adding biological therapy can further reduce the risk of the leukaemia coming back
  • Whether extra monitoring of some people is useful in trying to work out who has a higher chance of their leukaemia coming back

If you have a type of AML called acute promyelocytic leukaemia (APL) you have different treatment. This is described in A trial looking at treatment for acute promyelocytic leukaemia (AML 19)

Who can enter

The following bullet points list the entry conditions for this trial. If you are unsure about any of these speak with your doctor or the trial team. They will be able to advise you. 

You may be able to join this trial if you have one of the following 

  • Acute myeloid leukaemia
  • High risk Myelodysplastic syndrome (more than 10% of your bone marrow is made up of immature cells called blasts)

As well as the above all of the following apply. You

  • Are well enough to be up and about for at least half the day (performance status 0, 1 or 2
  • Are suitable for intensive treatment
  • Have satisfactory blood test results
  • Are willing to use reliable contraception during treatment and for 1 month afterwards if there is any chance that you or your partner could become pregnant
  • Are aged between 18 and 60 years, older people may be able to take part if your doctor thinks you can have intensive treatment

Your blood tests include tests to check whether your liver is working normally. If these results are abnormal, you might still be able to take part in the trial. But you might not be able to have one of the drugs used this trial called mylotarg (gemtuzumab ozogamicin). 

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

  • Have already had chemotherapy to treat your AML, you can still take part if you have had hydroxycarbamide, or a similar low dose treatment to control you white blood cells
  • Have had treatment with a hypomethylating agent such as azacitidine or decitabine, you can still take part if you had this treatment for low risk MDS, which has transformed into AML 
  • Are in the blast phase of chronic myeloid leukeamia 
  • Have any other cancer that needs treatment 
  • Are HIV (Human Immunodeficiency Virus) positive 
  • Are pregnant or breastfeeding

Trial design

This is a phase 3 trial. The researchers need 3000 people to join. 

There are a number of different treatments described in this trial summary, not all are relevant to your situation. 

Your treatment depends on

  • The type of leukaemia you have
  • How well your first induction chemotherapy works
  • Certain features of your leukaemia

You have most of your treatment through a drip into a vein. Your medical team will explain your individual treatment in more detail and how and when you have your drugs. 

At different points in the trial, people with AML are put into groups by computer. Neither you, nor your doctors can decide which group you are in. This is called randomisation.

Doctors look closely at the chromosomes in leukaemia cells. This is called cytogenetics Open a glossary item. They know that people with an abnormal chromosome will need different treatment to those who don’t have the abnormality.

Treatment for AML that has a chromosomal abnormality
Doctors know that people with an abnormal chromosome will probably need further chemotherapy after induction, followed by a stem cell or bone marrow transplant. 

To try to improve induction treatment in this group of people, the trial team will compare the standard treatment of 

with a new combination of 

  • daunorubicin and cytarabine called CPX-351

Twice as many people will be in the group having CPX-351.

Diagram for AML19

You have 2 courses of FLAG-Ida or CPX-351 about 4 weeks apart. A course of chemotherapy is also sometimes called a cycle of treatment

Your doctor may then recommend that you go on to have a transplant using the stem cells or bone marrow of a donor. If there are delays or difficulties in finding you a donor, you have further chemotherapy.

If you had FLAG-Ida for your first 2 courses, you have

If you had CPX-351 for your first 2 courses, you have 2 further courses of this treatment.

Treatment for AML that has no chromosomal abnormality
If your AML does not have a chromosomal abnormality you are put into 1 of 4 groups at random. You have 1 of the following

  • DA (Daunorubicin and Ara-C) and 1 dose of mylotarg (also called gemtuzumab ozogamicin)
  • DA and 2 doses of mylotarg
  • FLAG-Ida and 1 dose of mylotarg
  • FLAG-Ida and 2 doses of mylotarg

Diagram for AML19 no chromosomal abnormaility

You have 

  • DA treatment over 10 days or
  • FLAG-Ida over 7 days

This is your first course of induction treatment. 

A few weeks after your first course of chemotherapy, your doctor will look at samples of your blood and bone marrow to see if there are any leukaemia cells left behind. They will also look at other factors, such as the cytogenetics of your leukaemia, to decide the risk of your leukaemia coming back (relapse). 

If you have a higher than normal risk of your cancer coming back, this is called high risk disease. Your treatment will be different to those people who do not have high risk disease.

High risk AML
If you have high risk AML or MDS your doctor may recommend that you have a transplant using the stem cells or bone marrow of a donor. 

Before your transplant, or while you are waiting for a donor to be found, you have further chemotherapy. 

The trial team want to compare standard chemotherapy with CPX-351.

The standard treatment involves 3 different courses of chemotherapy, one after the other. These are 

Everyone in this part of the trial is put into 1 of 2 groups at random

  • One group has FLAG-Ida, MACE and MidAC 
  • The other group has 3 courses of CPX-351

Twice as many people will be in the group having CPX-351.

Diagram for AML19 high risk AML

You have each treatment about 4 weeks apart.

If you had FLAG-Ida as your induction treatment and your leukaemia did not go into remission, or has come back within the last 6 months you will have further chemotherapy. The standard drug used in this situation is fludarabine

In this trial you have fludarabine and CPX-351. You have these drugs

  • Over 5 days for your 1st course
  • Then over 3 days for up to 2 more courses

Not high risk AML 
If you do not have high risk disease, you have a second course of induction chemotherapy. This will be the same drugs as you had in course 1 (DA or Flag-Ida), but without Mylotarg.

If you had DA as your induction treatment and you are not at high risk you then have consolidation treatment. Your consolidation treatment is 2 courses of high dose Ara-C.

If you had FLAG-Ida as your induction treatment and you are not high risk, you then have consolidation treatment. This part is randomised. You have 1 of the following

  • 2 courses of high dose Ara-C
  • 1 course of high dose Ara-C
  • No treatment with Ara-C

Diagram for not high risk AML

You have Ara-C treatment over 5 days. 

If you have a 2nd course, you have this 4 to 6 weeks later.

Monitoring 
When you were first diagnosed you had a test to find out if your leukaemia or MDS has a certain marker. The doctors looked at a blood sample and a sample from your bone marrow test to do this.

If your leukaemia has this marker, the trial team will ask you whether you will take part in the monitoring randomisation. You may be high risk or not high risk, as long as your leukaemia has this marker. 

Your doctor does not know how reliable this marker is yet. It may be useful to predict whether your leukaemia or MDS is going to relapse. Everyone who agrees to this extra monitoring will be put into 1 of 2 groups at random.

  • One group will have extra monitoring
  • The other group will not have any extra monitoring

Twice as many people will be in the group having extra monitoring.

Diagram for AML19 monitoring

Everyone will have close monitoring and follow up appointments as part of their routine care. If you have extra monitoring, you have 8 extra bone marrow tests. Most of these will take place in the first year of your treatment. 

Your doctor or nurse will explain exactly when these tests are due. 

Your doctor will discuss the results of these tests and they may play a part in whether you have any further treatment. 

Everyone taking part in the monitoring randomisation will be asked to fill out a questionnaire on 8 different occasions over a period of 18 months. The questionnaire will ask various questions about your quality of life and about the extra monitoring if you have it.

Hospital visits

You will see the doctors and have some tests before you start treatment. The tests include 

You have the above tests again during and after your treatment.

Your treatment is very intensive and so you will spend a lot of time at hospital. You usually stay in hospital to have your chemotherapy, for at least 1 to 2 weeks each time, sometimes longer. 

If you are able to have your treatment as an outpatient, you will need to go to hospital quite often (for example 2 to 3 times a week) to have blood tests and to check how you are.

Your doctor or nurse will explain how often you need to visit hospital during and after your treatment

Side effects

The most common side effects of chemotherapy include

The most common side effects of Mylotarg include 

  • A change to the way your liver works. You will have regular blood tests to monitor this
  • A drop in the white blood cells causing an increased risk of infection
  • Fever and chills
  • Feeling or being sick
  • Headache
  • Breathlessness
  • High blood sugar Open a glossary item
  • High blood pressure or low blood pressure

The possible side effects of ganetespib include 

  • High temperature
  • Lung infection
  • Tiredness (fatigue)
  • Feeling sick
  • A drop in the number of red blood cells (anaemia Open a glossary item)
  • Loss of appetite
  • Diarrhoea

If you have any diarrhoea tell, your doctor or nurse straight away as this may need treating.

Location

Aberdeen
Airdrie
Basingstoke
Birmingham
Blackpool
Bradford
Bristol
Cambridge
Cardiff
Cheltenham
Chester
Coventry
Derriford
Dudley
Dundee
Edinburgh
Glasgow
Gloucestershire
Inverness
Leeds
Leicester
Lincoln
Liverpool
London
Manchester
Merseyside
Milton Keynes
Newcastle upon Tyne
Nottingham
Oldham
Oxford
Poole
Portsmouth
Romford
Rotherham
Salford
Taunton
Torbay
Wirral
Worcestershire

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Professor Nigel Russell

Supported by

Cancer Research UK
Cardiff University
Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer

Other information

This is Cancer Research UK trial number CRUK/13/35

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

11756

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Wendy took part in a new trial studying the possible side effect of hearing loss

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"I was delighted to take part in a clinical trial as it has the potential to really help others in the future.”

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