Acute lymphoblastic leukaemia research

All the new approaches covered here are the subject of ongoing research. Until studies are completed and these new treatments have been shown to work, they cannot be used as standard therapy for acute 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 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 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 within or outside the NHS.

Tests in patients are called clinical trials. There are 4 phases of clinical trials. This is fully explained in the trials and research section. If you are interested in taking part in a clinical trial, visit our searchable database of clinical trials in the UK. Choose ‘acute leukaemia’ from the drop down menu. If you are interested in one of the trials, 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.

New drugs are being developed all the time. It is most important that we know that these drugs work - and whether they work better than the treatments we currently use. For this reason, drugs have to go through a long testing process. You will often only be able to have new drugs within clinical trials. Early trials are often carried out with patients who have had all available treatment.

Clofarabine (Evoltra) is similar to another leukaemia drug already in use, fludarabine. It has been researched for children with ALL. It is licensed in the UK for treating people aged between 1 and 21, if they have already had at least 2 different courses of treatment, and the ALL has not responded or has come back. Clofarabine is now also being looked at in studies to see if it helps adults with acute leukaemia.

Doctors also investigate different combinations of chemotherapy drugs and different doses. Their aim is to get good results with treatment, but at the same time, not cause too many side effects. Trials are looking at different combinations and doses of chemotherapy.

The UKALL 2011 trial is looking at treatment for children and young adults (up to age 24) with ALL. The aims of this trial are to see if changing the standard treatment will reduce side effects and help stop the disease from coming back. 

The UKALL 14 trial is comparing treatments for adults between 25 and 65 years old who have recently been diagnosed with ALL. Doctors usually treat ALL with several different chemotherapy drugs, often in high doses, and sometimes with a stem cell transplant. The researchers are looking at changing the treatment in several different ways with the aim of improving treatment for adults with ALL. Trials for ALL are listed on our clinical trials database. Pick 'acute leukaemia’ from the drop down menu of cancer types.

Chemotherapy can affect your immune system, which helps to fight infection. Doctors know that children having chemotherapy for ALL are at increased risk of an infection called pnemococcus. A trial is looking at a vaccine to help protect against this infection in children who are having or have recently finished treatment for ALL.

One difficulty in treating leukaemia with chemotherapy is that the cancer gradually becomes resistant to the chemotherapy. In other words, treatment that worked before no longer does. This is because the cells of many cancers have an overactive gene called mdr1. This stands for multi drug resistance.

Cells that have this overactive gene create a protein that makes the cancer cell pump out any chemotherapy drug that gets inside. Some drugs have been tried that can overturn this, but they cause a lot of side effects. A new drug is now available. This is a slightly changed version of a drug called ciclosporin. This drug (known as PSC833) has had some success in trials. But it caused serious side effects in a phase 3 trial, so the trial was stopped early. Researchers are still trying to find better ways to use this and other drugs.

A chemotherapy drug called nelarabine (Atriance) may be used to treat people with T cell acute lymphoblastic leukaemia (T-ALL) and T cell lymphoblastic lymphoma (T-LBL). The disease must be resistant to standard treatment, or have come back (relapsed) after treatment with at least 2 chemotherapy combinations.

The ALL R3 trial is for children who have ALL that is not responding to treatment, or has come back (relapsed). It looks at different types of treatment including bone marrow transplant and chemotherapy. You can search for UK trials for children with ALL on our clinical trials database. Pick ‘children's leukaemia and lymphoma’ from the dropdown menu of cancer types.

Bone marrow and stem cell transplants for ALL 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 the ALL treatment section. Bone marrow or stem cell transplants give the best chance of controlling the ALL 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 transplants are for people who don't have a relative or unrelated donor 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.

Most people have platelet transfusions to prevent bleeding during treatment for ALL. Chemotherapy can slow 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 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 is finding out whether it is safe to wait until you have early signs of bleeding, such as bleeding gums, before having a platelet transfusion. The researchers want to find out if people who have a low platelet count, but no signs of bleeding really need platelet transfusions. The aim is to compare different ways of using platelet transfusions. This may affect the way doctors use them in the future.

Biological therapies use substances that the body makes naturally to treat cancer. There are different types of biological therapy including 

• Tyrosine kinases
• Monoclonal antibodies

Tyrosine kinases

Tyrosine kinase inhibitors (TKIs) are one type of biological therapy for ALL that researchers are looking at.

Tyrosine kinases are chemicals that cells use to signal to each other. Some of these signalling systems tell cancer cells to grow and divide. Scientists have been working on drugs called tyrosine kinase inhibitors (TKIs) that block these signals.

Imatinib mesilate (Glivec) is a TKI drug licensed in the UK to treat chronic myeloid leukaemia (CML). It is now also licensed to treat  people with ALL who have a particular chromosome change called the Philadelphia chromosome. In ALL, about 1 in 5 people (20%) have the Philadelphia chromosome. Research studies show that having imatinib as part of your first phase of treatment (remission induction therapy) improves your chances of getting into remission. Researchers continue to look at imatinib, as well as other TKI's.

The EsPhALL trial is looking at imatinib for children aged between 1 and 17 with Philadelphia chromosome positive leukaemia. 

Another TKI researchers are looking at is dasatinib. The CA180226 trial is looking at dasatinib to treat children and young people (20 or younger) who have Philadelphia chromosome positive ALL that is not responding to imatinib (Glivec). The researchers want to find out how well dasatinib works for this group and to learn more about the side effects. The CA180372 trial is looking at dasatinib for children and young people who have just been diagnosed with ALL that has the Philadelphia chromosome.

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 ALL. It is for people 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.

Monoclonal antibodies

Other types of biological therapy include monoclonal antibodies. Monoclonal antibodies can seek out cancer cells by looking for particular proteins on the cell’s surface. The MARRALL study is looking at adding the monoclonal antibodies veltuzumab and epratuzumab to chemotherapy to treat acute lymphoblastic leukaemia (ALL) that has come back. The main aim of this study is to see if adding veltuzumab and epratuzumab to standard treatment for ALL that has come back is safe.

A trial is looking at blinatumomab for people who have pre B cell ALL. When you finish chemotherapy you have tests to see how it has worked. Although these may show that your ALL has gone away (in remission), it may start to grow again. Doctors hope blinatumomab will stop ALL from starting to grow again.

There is another trial looking at blinatumomab for people with pre B cell ALL that has not responded to treatment or has come back after treatment.

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

Babies are sometimes diagnosed with ALL. Trials have shown that treatment with chemotherapy and steroids works quite well, but sometimes the leukaemia comes back. 

Another trial is now looking into whether some babies need more intensive treatment. Babies may join the INTERFANT-06 trial if they have ALL or mixed type (biphenotypic) leukaemia, and are less than one year old. After their first round of chemotherapy treatment, doctors will decide if the babies have a low, medium or high risk of their leukaemia coming back. They will do this by looking at the baby's age, their white cell count, how well they have responded to treatment so far, and whether there is a particular genetic change in their leukaemia cells. Babies who are in the low risk group will continue to have standard treatment. But those at medium and high risk will be put into different groups to look at how well different treatments work at stopping the leukaemia coming back. Some babies will have more intensive chemotherapy, and some will have a transplant of their own stem cells (autologous stem cell transplant). There is more information about this trial on our clinical trials database.