Focus on Acute Myeloid Leukaemia – AML 18 and AML 19 explained

The purpose of a clinical trial is to discover if a new treatment or procedure is safe, has side effects, or is more effective than the current treatment.

Patients and their families will be given a huge amount of information at the time of diagnosis of acute myeloid leukaemia (AML).

You will need to know what acute leukaemia is, what treatments are available and how the treatments will be delivered. This information is normally given by your haematology team, to yourself and your family within a very short period and consists of a discussion with the doctor and specialist nurse. Written information will also be given which explains all about AML.

At the same time, you may also be asked to consider taking part in one of the current national studies, such as the AML 18 or AML 19 trials. Acute myeloid leukaemia studies are complex and have several different treatment options available, which patients may be allocated as they go through each course of treatment.

When you are asked to consider taking part in a clinical trial, it is important to read the patient information sheet provided in order to understand why the research is being done and what it will involve. Reading through lots of complex information around this time places more stress upon the patient and their family. It is important that this information is given in a way that can be explained well, so that you are able to make informed decisions supported by your haematology team.

AML 18 Trial

– For older patients with AML and High Risk Myelodysplastic Syndromes (MDS), and for patients who are fit to receive to intensive chemotherapy

This trial is open to patients across the UK in several treatment centres and some other countries.

AML 18 is a Phase III trial which will compare two induction (initial) treatments. The aim of the induction treatment is to kill off the leukaemia cells so that the bone marrow can work normally, which is called disease remission. Written consent to enter the study will be required with additional consent for blood and bone marrow tests to be carried out as part of the study follow up.

The first course of treatment includes a two-drug combination called Daunorubicin/AraC (DA); this is the standard treatment. Along with this chemotherapy, the research question is asking if using a targeted treatment (monoclonal antibody) called Mylotarg could be beneficial. Previous research of adding Mylotarg to chemotherapy has demonstrated an improvement in survival of this patient group. The research question asks if two doses of Mylotarg with DA chemo is better than one dose of Mylotarg and DA chemo.

Following the first course of treatment, a bone marrow test and blood test will be carried out to look at how well the treatment has worked and if complete remission has been achieved. The blood and bone marrow tests will be checking to see if there are still residual leukaemia cells remaining (MRD). Before starting course two, your Haematologist will discuss the possibility of receiving a new treatment small molecule through randomisation.

Patients who are MRD negative will have a further course of DA chemotherapy and possibly the small molecule AC220.

Patients who have some leukaemia cells remaining (MRD positive) will also be eligible to possibly have the new additional targeted treatment with chemotherapy, which is either a combination of Cladribine or Flag Ida for up to two courses of therapy.

Further bone marrow and blood tests may be needed following each course of treatment as part of the clinical trial schedule for MRD monitoring. Each stage of the study will be discussed with your by your Haematologist and specialist nurse to check that you are to continue with the study. Please ask your specialist team any questions that you may have.

Information and booklets which describe the trial are available for patients, their families and healthcare professionals.

AML 19 Trial

– For adults with AML or High Risk MDS aged 18 to 60 years, and for patients aged 60 years or over for whom intensive therapy is considered appropriate

If you are on the AML 19 trial, you will receive intensive induction chemotherapy like the patients who enter the AML 18 trial, following written consent to enter the study.

In this study, the first two courses of treatment, called the induction phase, will consist of two combinations of chemotherapy drugs which are being compared, called DA (Daunorubicin and Ara-C), or FLAG-Ida (Fludarabine, Ara-C, G-CSF and Idarubicin). Both combinations have been widely used and have already been extensively tested and given to hundreds of patients.

Again, similar to AML 18, this study will also compare if adding one or two doses of Mylotarg to standard treatment (DA or FLAG-Ida) is better. Therefore, patients will also receive one dose or two doses of Mylotarg with the first course of chemotherapy. This study will compare the treatments against each other to improve the outcomes for patients with AML.

Both combinations have been widely used before to treat AML and within the study, a comparison will be made comparing both groups of patients who received chemotherapy alone.

When remission is achieved in AML, there is still a risk the leukaemia can come back (known as relapse). To try to prevent this, more courses of chemotherapy will need to be given to kill off any leukaemia cells that got missed in the first treatment courses. This is called consolidation treatment. In consolidation, different treatments will be compared against each other with the aim of finding out which treatment is best at preventing relapse and for what patients.

Once the first course of chemotherapy has been completed, a bone marrow and blood test will be carried out to see how well the treatment has worked. Information about the risk of relapse, along with the bone marrow test results, will be discussed so that the next treatment course can go ahead. For some patients, a stem cell transplant will be advised, whilst for others this may not be necessary. This is quite a complicated decision which will be discussed when the time comes.

There are new methods of monitoring the disease, but we are not sure how useful they are and whether by using them the outcome of treatment will be improved. There will be an option to be in one group that will have extra bone marrow tests, but your doctor will discuss if it is appropriate for you to enter this part of the study.

At each stage of the study, usually at the end of each treatment, there will be information sheets available to explain the next steps and course of treatment. These options will be discussed with you and your haematology team.

This is a summary of the current AML clinical trials. These studies are constantly being amended when new therapies are available, in order to improve our treatments and patient outcomes.

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