Chronic myeloid leukaemia (CML) research

All potential new treatments have to be fully researched before they can be adopted as standard treatment for everyone. This is so that

• We can be sure they work
• We can be sure they work better than the 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 patients. 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 within or outside the NHS.

Tests using patients are called clinical trials. The trials and research section has information about what trials are including information about the 4 phases of clinical trials. 

All the experimental treatments on this page are the subject of ongoing research. Until clinical studies are completed, doctors will not know whether any of the new treatments work any better than the existing standard treatments. Until they have completed these clinical trials, the experimental treatments cannot be used as standard treatment for chronic leukaemia because we do not yet know how well they work.

If you are interested in taking part in a trial, visit our searchable database of clinical trials. Choose 'leukaemia: chronic' from the dropdown menu. If there is a trial you are interested in, 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. Leukaemia is a big area of cancer research and most major treatment centres are continually involved in clinical trials.

Most cancers, including leukaemia, will vary from person to person in how quickly or slowly they grow. Researchers have identified some factors that can help to tell doctors how the disease is likely to develop. Doctors can use this type of information to help them decide on the most suitable treatment for you. They call these factors prognostic factors because they influence the likely course of your disease and treatment.

There have been several systems developed over the years for trying to work out how CML will develop. One system that doctors use is called the Sokal Index (it is named after the doctor who created it). It looks at your platelet count, the number of leukaemia cells in your blood, your age and the size of your spleen. The Sokal Index can help doctors to decide who should have more intensive treatment at an earlier stage.

There are different types of biological therapies. One group of biological therapies are described as cancer growth blockers. The different types of cancer growth blockers are named after the type of chemical that they block inside the cell. Tyrosine kinase inhibitors are often called TKIs. They block (inhibit) chemical messengers (enzymes) called tyrosine kinases. Tyrosine kinases are part of the signalling process within cells. Blocking this process stops the cell growing and dividing. Cancer growth blockers can block one signal, a single TKI, or more than one signal, a multi TKI.

Imatinib

The biological therapy imatinib (Glivec) is now the most commonly used treatment for CML. But doctors and researchers continue to try to improve the results of the treatment they use. Another stage of Glivec research is to see if it works even better when combined with other treatments, such as chemotherapy or immunotherapy. The SPIRIT trial has been comparing different doses of Glivec, and Glivec in combination with the immunotherapy drug interferon. This trial is no longer recruiting patients, and we are waiting for the results. The CHOICES trial is combining a drug called hydroxychloroquine with imatinib for chronic myeloid leukaemia that has already responded well to imatinib.

Many people respond well to imatinib. But even if you have a very good response, there may be a small number of leukaemia cells left in your body. This is called residual disease. Doctors can see if there is any residual disease using a test called polymerase chain reaction (PCR) which looks for genetic changes in cells.

The people taking part in the CHOICES trial have had a good response to imatinib, but their doctors can see there are still some cancer cells by doing a PCR test. Everybody taking part will carry on having imatinib, but some people will also start taking hydroxychloroquine.

There is information about this trial on our clinical trials database. There is more information on Glivec for CML in this section of CancerHelp UK.

Newer biological therapies

Other biological therapies similar to Glivec are being developed. There are two called dasatinib and nilotinib (Tasigna). Early research into these drugs suggests that they could be much more powerful than Glivec. In early trials with patients, dasatinib helped to control CML that had not responded to Glivec, or had become resistant to it. 

One trial is looking at nilotinib for newly diagnosed chronic myeloid leukaemia. It is for people who are Philadelphia chromosome positive, or have a high level of a protein called BCR-ABL (or both) and whose CML is in chronic phase. The researchers are trying to find out more about having nilotinib as the first treatment after being diagnosed with CML. They aim to see if CML in chronic phase responds better to nilotinib as a first treatment than it does to imatinib. They also want to learn more about the different ways people respond to nilotinib treatment. 

The SPIRIT 2 trial is comparing imatinib with dasatinib for people with newly diagnosed chronic phase CML. There is also a trial looking at nilotinib for newly diagnosed CML. This trial compares nilotinib with imatinib. The people in the trials have been followed up for a year and the initial results are promising but it is too early to say whether they will do better in the long term. 

The CA180226 trial is looking at 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. You can find out about these trials on our clinical trials database.

Both dasatinib and nilotinib have been licensed in Europe for treating CML. They can be used to treat CML in people who cannot have Glivec because of side effects, or who have had Glivec and their CML has not responded. Both drugs have also been approved by the Scottish Medicines Consortium (SMC) for use on the NHS in Scotland, but only for people in chronic phase of their disease. 

In December 2007, the All Wales Medicines Strategy Group (AWMSG) approved the use of dasatinib in the NHS in Wales, for people with CML which cannot be treated with Glivec, if they are in the chronic or accelerated phase of the disease, but not blast phase. The National Institute for Health and Clinical Excellence (NICE) have said that nilotinib should be available for use on the NHS in England. They only recommend it when imatinib is no longer working or the side effects of imatinib are severe. It is only be available as part of the patient access scheme. The patient access scheme is when the manufacturer agrees a reduced price of a drug for the NHS. NICE have said that dasatinib should not be available for use within the NHS at stage of disease or when imatinib is no longer working.  

In December 2010, the license for dasatinib in Europe was extended so that the drug can be a first treatment for people in the chronic phase of CML. This is following research which shows dasatinib may work better than imatinib. The AWMSG have said that it should not be available as a first treatment within the NHS in Wales because they say it is not cost effective. Dasatinib has not been approved by NICE or the SMC for use as a first treatment in the NHS. 

An early phase trial called CA 180018 looked at children and young people under 20 with Philadelphia positive CML. It was for people whose disease was no longer responding to Glivec. And to anyone under 20 with any type of leukaemia which had come back, and for which there is no more treatment available. This trial is now closed and we are waiting for the results.

Ponatinib

Another biological therapy being investigated is called ponatinib. It is a new type of tyrosine kinase inhibitor. It is different to previous TKIs in that it affects a mutation called T3151 found in some people with CML. This genetic mutation is very resistant to treatment and other drugs available do not really work in patients with this mutation. Ponatinib blocks cells that have this mutation, and in early lab tests it appeared to prevent T3151 or other mutations forming. 

The PACE trial is looking at ponatinib for Philadelphia positive CML. It is for people who have accelerated phase CML with the T315I mutation. This research is a phase 2 study in patients who have become resistant to dasatinib and nilotinib. Ponatinib is a tablet and so far does not seem to cause severe side effects.

People with leukaemia often have platelet transfusions during their treatment. These are to prevent bleeding. Chemotherapy can slow down the production of platelets by the bone marrow, so you have fewer of them circulating in your blood. If your platelet level gets very low, you can bruise easily, have nosebleeds or bleed more than usual from cuts or grazes. Doctors check your level of platelets regularly while you are having chemotherapy. If they are very low, you normally have platelet transfusions through a drip.

Doctors do not yet know if people need these platelet transfusions to prevent bleeding. There are small risks linked to having platelet transfusions. Some people have a reaction to the platelets and sometimes this can be serious. Also, there is a small risk of getting an infection.

A trial in the UK is finding out if it is necessary to give preventative platelet transfusions, when there are no signs of bleeding. Or whether it is safe to wait until you have early signs of bleeding, such as bleeding gums, before having a platelet transfusion. The aim is to compare different ways of using platelet transfusions. This may affect the way doctors use them in the future. 

You can find out about trials for CML on our clinical trials database. Click on 'chronic leukaemia' in the dropdown menu of cancer types.

Most people with CML have leukaemia cells that carry the Philadelphia chromosome. This chromosome has an abnormal gene that tells the cell to make a protein called bcr/abl. CML cells have this protein on their surface. Your immune system should recognise the protein and then know that these cells are not normal. But usually, this immune reaction is very weak in CML, if it happens at all. Doctors are trying ways of helping the immune system to find these abnormal cells. They are making copies of parts of the protein and using them to vaccinate people with CML. They hope that the vaccinations will kick start the immune system and that hopefully more CML cells will be destroyed.

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 A2 (HLA A2). The researchers hope the vaccine injection will help boost the immune system to recognise and kill leukaemia cells. 

There are trials looking at a new chemotherapy drug called omacetaxine. Omacetaxine is also called Homoharringtonine or CGX-635. It is given as an injection under the skin. 

A recent trial of omacetaxine for chronic myeloid leukaemia with the T3151 gene mutation was for people who had  already had treatment with imatinib. People with the T3151 mutation are less likely to respond to imatinib. This trial has now closed and we are waiting for the results.

Another recent study was a trial of omacetaxine for chronic myeloid leukaemia in people who could not take tyrosine kinase inhibitors (TKIs) or whose leukaemia had not responded to TKIs. This trial was for people with CML who had already had treatment with 2 different tyrosine kinase inhibitors (TKIs), for example imatinib, but their disease had not responded, or had become resistant to these drugs. This trial was also for people who could not take TKIs because they had severe side effects. This trial has now closed and we are waiting for the results.

Donor transplants are still the only known cure for some people with CML, but some people do not survive the complications of transplants.  Because of the encouraging results with Glivec, doctors think very carefully about who they should offer transplants to. We know from research that those most likely to do well after a transplant are CML patients under 45 years old with a brother or sister who is a full match OR those under 35 with a fully matched donor who is not a relative.

Because of the success of Glivec, these days some specialists prefer to treat everyone with this drug and see how they do. They are only likely to consider transplant in people whose CML does not respond fully to Glivec.

Doctors are looking at improving how they do bone marrow and stem cell transplants for chronic leukaemia. They would like to lessen the side effects if possible, as they can be severe and even life threatening.

There is a new procedure called mini transplant being investigated for people with leukaemia. Some doctors call this RIC transplant, which stands for reduced intensity conditioning. This type of treatment is still experimental.

With a mini transplant, the chemotherapy doses are not as high as with a regular transplant, so the side effects are not as severe. After the chemotherapy, you have bone marrow cells from someone else (a donor). The chemotherapy treatment you've had suppresses your immune system and allows the donor's blood stem cells to start producing blood cells. The donor cells see your CML cells as foreign (because they are yours and not the donor's) so they kill them.

Because the chemotherapy doses are lower, your own marrow cells can continue to grow after a mini transplant. If this happens, you need to have more white blood cells from your donor. As with your transplant stem cells, you have these through a drip into a vein. Doctors call this donor lymphocyte infusion or DLI. The donor T cells will attack any remaining leukaemia cells. Doctors call this the graft versus disease effect, or graft versus leukaemia effect (GvL). The graft means the donor T cells. 

There has been a trial looking into mini transplant in people who have chronic phase CML. After their transplant, the patients in this trial have Glivec. The doctors then hold off on the donor white cell infusions for a while. This lowers the risks of severe side effects from the white cell infusions, such as graft versus host disease (GVHD) and low blood cell counts. There has been another small trial looking at having a mini transplant followed by Glivec for a year, to see if this reduces the chance of the CML coming back. The researchers found that imatinib increased the amount of time before the CML came back. And there was a low risk of side effects with this combination of treatment.

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 mini transplant. 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. 

You can find out about these trial on our clinical trials database.

One problem with treating leukaemia is that even if you seem to have been successfully treated, there can be very small numbers of leukaemia cells left behind. The numbers are so small that the usual blood and bone marrow tests cannot pick them up. You may hear your doctor call this minimal residual disease (MRD).

Scientists are exploring new ways of finding out if there are leukaemia cells left behind after the disease appears to have clinically gone (remission).

One way of doing this is with a test called the polymerase chain reaction (PCR). This test can find one leukaemia cell among a million normal cells. It can help doctors to find out how well your chemotherapy has worked in killing off your leukaemia cells. This test can help to tell the doctor whether your leukaemia is likely to come back (relapse).