Acute myeloid leukaemia research

All the new approaches covered here are the subject of ongoing research. Until studies are completed and we know these new treatments work, they cannot be used as standard therapy for acute myeloid leukaemia.

We must fully research all potential treatments before we can adopt them as standard treatment for everyone. This is so that

• We can be sure they work
• We can be sure they work better than treatments that are available at the moment
• They are known to be safe

First of all, treatments are developed and tested in laboratories. For ethical and safety reasons, experimental treatments must be tested in the laboratory before they can be tried in people. If a treatment described here is said to be at the laboratory stage of research, it is not ready for patients and is not available either in the NHS or in private healthcare organisations.

Tests in patients are called clinical trials. There are 4 phases of clinical trials. This is fully explained in the understanding clinical trials section. If you are interested in taking part in a clinical trial, visit our searchable database of clinical trials in the UK and choose ‘Leukaemia: acute leukaemia’ from the dropdown menu.

If you are interested in one of the trials, you can print it off and take it to your own specialist. If the trial is suitable for you, your doctor will need to refer you to the research team. The database also has information about closed trials and trial results. Most major leukaemia treatment centres are continually involved in clinical trials.

Clofarabine (Evoltra) is a new chemotherapy drug similar to fludarabine, a leukaemia drug already in use. A recent trial found that clofarabine works well for people who are older and not able to have the usual intensive chemotherapy for acute myeloid leukaemia (AML). Part of the AML16 trial is trying to find out if clofaribine is better than other treatments for older people with AML. 

Azacitidine (Vidaza) is used for some blood disorders and is being tried after mini transplant for AML. Decitabine is a drug similar to azacitidine. The DEC-MDS trial is looking at decitabine for myelodysplastic syndrome and acute myeloid leukaemia. The trial aims to find out how well decitabine works for people with MDS and AML and to find out about its side effects.

A drug made from arsenic has been developed and is licensed in the UK for treating a type of acute leukaemia called acute promyelocytic leukaemia. The drug is called arsenic trioxide. At the moment, this drug is only licensed for people who have acute promyelocytic leukaemia that

• Has come back (relapsed) even after successful treatment
• Is resistant to treatment – this means that leukaemia cells are still in the bone marrow after you've had standard treatment

You might be offered this treatment if you have had chemotherapy and a drug called ATRA, but your acute promyelocytic leukaemia has either come back or has not responded to the treatment.

The CLAVELA trial is looking at whether a drug called elacytarabine can help people with AML. The trial is using elacytarabine for people with AML that has not responded to treatment, or has come back after 2 or 3 other types of treatment.

The AML LI-1 trial is looking at 2 new chemotherapy drugs, sapacitabine and vosaroxin. The researchers are also looking at a new biological therapy called AC220, which is a type of tyrosine kinase inhibitor. The researchers think that these drugs alone or in combination with cytarabine may be better than cytarabine alone for people with AML who can't have intensive treatment.

The VALOR trial is also looking at the new chemotherapy drug vosaroxin. Doctors want to find out if vosaroxin and cytarabine together is better at treating AML that has not responded to treatment or has come back after the first treatment than cytarabine alone.

As well as new drugs, doctors also investigate different combinations of chemotherapy drugs and different doses. Their aim is to get good results with treatment, but not to cause too many side effects.

There is detailed information about these trials on our clinical trials database. Pick 'Leukaemia: acute leukaemia' from the dropdown list.

Bone marrow and stem cell transplants can work well for acute leukaemia. But the intensive chemotherapy can be so difficult that only very fit patients can cope with it. Now, doctors are looking at a new, less harsh type of transplant.

Doctors know that leukaemia is less likely to come back in people who have a donor transplant and get a reaction called graft versus host disease (GVHD). In GVHD the donor blood cells attack the patient's own cells, including the leukaemia cells. Doctors call this the graft versus leukaemia (GVL) effect.

The mini transplant makes use of the graft versus leukaemia effect. The chemotherapy doses you have are too low to destroy your own bone marrow. You have just enough chemotherapy to damp down your marrow until the donor cells have settled into it and started to produce blood cells. The aim is that you develop mild GVHD so the donor cells can attack and kill the leukaemic cells. Although this treatment helps more people to live longer than a full transplant, you still need to be fairly fit. The GVHD can be tough to cope with. Mini transplants have been part of the AML15 trial. This trial is no longer recruiting patients, and we are waiting for the results.

The MUNICH trial is looking at giving reduced intensity stem cell transplant 3 days after chemotherapy for acute myeloid leukaemia (AML). This trial is for people with AML that has not responded to treatment or has come back after treatment. Giving the treatment in this way reduces the amount of time people spend in hospital. The aims of the trial are to find out how well reduced intensity transplant works for these conditions and what the side effects are.

You can find information about trials using transplants for AML on our clinical trials database. Go to the advanced search and choose 'leukaemia – acute leukaemia' from the dropdown menu of cancer types and 'chemotherapy' from the dropdown list of treatment types. If you want to see all the trials, tick the boxes for closed trials and trial results.

Bone marrow and stem cell transplants for AML use high dose chemotherapy, and sometimes total body radiotherapy. This treatment kills off all the stem cells inside your bone marrow that make all your blood cells. You have the stem cells replaced by a drip of stem cells or bone marrow. You can have someone else’s bone marrow or stem cells, or your own bone marrow. There is detailed information about bone marrow and stem cell transplants in this section. Bone marrow or stem cell transplants give the best chance of controlling the AML for a long time in some people. But the high dose treatment can also cause severe side effects. Doctors are trying to find ways of improving these treatments. 

The RIC UCBT trial is looking at using stem cells collected from the umbilical cords of newborn babies. The cells are given to people after a transplant that uses lower doses of chemotherapy than usual (reduced intensity conditioning). These cord blood transplants are for people who don't have a relative who can be their stem cell donor. Doctors hope that the umbilical cord stem cells will cause fewer side effects than adult stem cells. 

The MAC UCBT trial is also looking at using umbilical cord blood from unrelated donors after high dose chemotherapy.You can find out about these trials on our clinical trials database.

Natural killer (NK) cells are a part of the immune system. They can target and attack any leukaemia cells left behind after chemotherapy. But some leukaemias are resistant to them. There is a small trial to find out if giving NK cells from a relative can reduce the risk of the leukaemia coming back. This is a new type of treatment, and the researchers also want to make sure it is safe. Your relative's tissue type must be a close match for yours. 

Doctors hope they can change the NK cells so that they stay in your immune system, and attack the leukaemia cells, but leave your normal cells alone. These changed NK cells are known as tumour activated natural killer cells, or TaNKs. They also hope these changed TaNK cells will be less likely to attack your body's normal cells and cause graft versus host disease (GVHD). You will also have chemotherapy and radiotherapy before receiving the donor cells, but in lower doses than you would if having a stem cell or bone marrow transplant.

Treatment for AML varies with age. You have to be very fit to get through some of the intensive treatments, so doctors don’t generally use them for older people. The older you are, the less likely you are to be fit enough. The good news is that as we get better at managing the effects, intensive treatments are being used more for older people.

Doctors think about treatment and the possible effects individually for each patient. You can be in your 50s and not as fit as some people who are in their 60s or even older. Whether you can have a transplant also depends on whether you have a brother or sister fit enough to be a donor. As you get older, the chance of having a donor who is fit enough gets lower.

The AML16 trial was focusing on people over 60 who had AML or a type of related condition called myelodysplastic syndrome (MDS). AML16 was in 2 parts

• Intensive treatment
• Non intensive treatment

The trial tested different combinations of treatment to see which worked best for older people with AML. The trials team have results from some of the drug combinations they looked at, which you can read from the links above. They are still analysing the results for some of the drugs used.

A trial called the SPARK trial is looking at treatment for people over 60 with AML who can't have intensive treatment. One of the less intensive treatments doctors use is a low dose of the chemotherapy drug cytosine arabinoside (also known as LDAC). This helps some people, but researchers are looking for ways to improve treatment. In this study they are looking at a new drug called AZD1152. The aims of the study are to see if AZD1152 works better than low dose cytosine arabinoside for people who can’t have intensive induction treatment for AML. And also to find out if a combination of the 2 drugs is better than cytosine arabinoside alone for people in this situation.

Another trial is comparing azacitidine with the usual treatment for people over 65 with AML. Azacitidine is a type of chemotherapy. Doctors often use cytarabine and an anthracycline drug such as daunorubicin. But this doesn't always work in older people with AML. Researchers think that azacitidine may be better than this usual treatment. 

There is detailed information about both trials on our clinical trials database. Pick 'Leukaemia: acute leukaemia' to find it.

Most people have platelet transfusions to prevent bleeding during treatment for AML. Chemotherapy can slow down the production of platelets by the bone marrow. If the level of platelets gets very low, you may bruise easily, have nosebleeds, or bleed more than usual from cuts or grazes. Doctors will check your level of platelets and, if they are very low, you will normally have platelets through a drip.

Doctors don't really know if these platelet transfusions are needed to prevent bleeding. There are small risks associated with platelet transfusions. Some people have a reaction to the platelets and this can sometimes be serious. There is also a small risk of getting an infection from transfusions.

The TOPPS trial in the UK is trying to find out if people who have a low platelet count, but no signs of bleeding, really need platelet transfusions, or whether it is safe to wait until you have early signs of bleeding, such as bleeding gums, before having a platelet transfusion. This may affect the way doctors use platelet transfusions in the future. You can read more about this trial on our clinical trials database. Click on ‘Leukaemia: acute leukaemia’ in the drop down menu of cancer types.

Aspergillosis is a chest infection caused by the aspergillus fungus. Chemotherapy and stem cell transplants weaken your immune system, which means you have a higher risk of getting aspergillosis. At the moment, the only way to be sure you have this infection is to have a test called a bronchoscopy. This involves putting a tube down your windpipe and into your lungs to take samples. You have a local anaesthetic or a drug to make you drowsy before the bronchoscopy. But it can still be uncomfortable.

There is a trial testing 2 new ways of checking for aspergillus. One is a blood test and the other is a breath test. Researchers want to see how good these tests are at finding aspergillus infection in people with acute leukaemia. There are more details about this trial on our clinical trials database.

Biological therapies treat cancer with substances that the body makes naturally. Biological therapies studied in acute leukaemias include

• Monoclonal antibodies
• Tyrosine kinase inhibitors
• Drugs that block cell growth
• Immunotherapy
• Lenalidomide
• Everolimus
• DNA vaccine

You can read about AML biological therapy trials on our clinical trials database. Go to the advanced search and choose 'acute myeloid leukaemia' from the dropdown menu of cancer types and 'biological therapies' from the list of treatment types. If you want to see all the trials, tick the boxes for closed trials and trial results.

Monoclonal antibodies

Monoclonal antibodies recognise and find specific abnormal proteins on the outside of cancer cells. Each monoclonal antibody targets one particular protein. Different types of cancer have different abnormal proteins.

Gemtuzumab ozogamicin (Mylotarg) is a monoclonal antibody attached to a chemotherapy drug called calicheamicin (pronounced cal-ick-ee-my-sin). The monoclonal antibody helps to deliver calicheamicin straight to cancer cells. Doctors in the UK are looking at it as a treatment for AML as part of the AML 17 trial. 

Tyrosine kinase inhibitors

Tyrosine kinases are a group of chemicals that cells use to signal to each other. Some signalling systems tell cells to grow and divide. Cancer cells send out too many of these signals. Drugs called tyrosine kinase inhibitors (TKIs) block the signals.

About 3 out of 10 people (30%) with AML have a genetic mutation that causes their cells to make too much of a tyrosine kinase inhibitor called FLT3. Researchers are trying different TKIs to block FLT3 and so help to control AML in these people. As part of  the AML 17 trial doctors are looking at a drug called CEP-701. They think that CEP-701 may help stop the FLT3 gene making too much tyrosine kinase. 

The CA180226 trial is looking at a type of TKI called dasatinib to treat children and young people (20 or younger) who have Philadelphia chromosome positive leukaemia that is not responding to imatinib (Glivec). The researchers want to find out how well dasatinib works for Philadelphia positive leukaemia in children and young people. They also want to learn more about the side effects in this age group. 

There is also a trial looking at a TKI drug called midostaurin (also known as PKC412) for people who have mast cell leukaemia (a very rare type of AML). The trial aims to find out if midostaurin helps people with mast cell leukaemia and to learn about how it works and its side effects.

Drugs that block cell growth

Doctors are using a new type of biological therapy called panobinostat. Panobinostat is also known as LBH589 and it aims to stop cancer growing by blocking enzymes called deacetylases (pronounced dee-as-et-isle-azes). It is a type of deacetylase inhibitor. Cells need these enzymes to grow and divide. Blocking them may stop cancer growing. There is a trial looking at panobinostat (also known as LBH589) for acute myeloid leukaemia (AML) that is not responding to other types of treatment. The aims of this study are to find out how much panobinostat helps people with AML that is not responding to treatment. And it also wants to learn more about the side effects.

Immunotherapy

Histamine is a chemical found in the body which helps the immune system to work, and is also involved in allergic reactions. Interleukin-2 (IL-2) is another chemical which is a natural part of the immune system. These chemicals can be made in large quantities in a laboratory and used as a type of immunotherapy. Histamine (as a drug called Ceplene) has now been licensed in Europe, together with IL-2, as a treatment to help stop AML coming back after chemotherapy, if it is in remission for the first time. 

In trials this treatment improved the time that patients stayed in remission. It works by helping to protect the body's own immune cells, which are responsible for killing any remaining leukaemia cells. We won't know if Ceplene will be available on the NHS until it has been looked at by The National Institute for Health and Clinical Excellence (NICE).

Lenalidomide

Another new treatment which researchers are looking into is lenalidomide (Revlimid). This drug works mainly by helping the body's immune system target cancer cells. We know from earlier research that lenalidomide can help people with low risk myelodysplastic syndrome (MDS) where chromosome 5 is missing. Researchers think it may help people with high risk MDS or AML who have a chromosome 5 abnormality. A study called Len5 is looking at it as a treatment on its own or in combination with chemotherapy. The aims of this study are to find out if it is safe to have, to learn more about the side effects, and to find out if it helps people with AML or high risk MDS. The trial has closed and we are waiting for the results.

Everolimus

Doctors also think that another biological therapy called everolimus may also help people with leukaemia. Everolimus works by stopping a particular protein called mTOR from working properly. mTOR controls other proteins that trigger cancer cells to grow. So everolimus may help stop the cancer from growing, or slow it down. The AML 17 trial is looking at everolimus and a number of other biological treatments mentioned above for people with AML under the age of 60. It is part of a larger trial looking at other types of acute myeloid leukaemia such as acute promyelocytic leukaemia (APL), high risk myelodysplastic syndrome, and AML in children.  

DNA vaccine

The WIN study is looking at a possible vaccine treatment for people with acute myeloid leukaemia (AML), and chronic myeloid leukaemia (CML). The vaccine is for people with a form of a gene called Human Leucocyte Antigen (HLA A2). The researchers hope the vaccine injection will help boost the immune system to recognise and kill leukaemia cells. 

You can find out about biological therapy trials for AML on our clinical trials database, choose 'AML' from the dropdown list.