A trial looking at improving treatment for children and young adults with acute lymphoblastic leukaemia (EsPhALL2017)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Acute leukaemia

Acute lymphoblastic leukaemia (ALL)

Blood cancers

Children's cancers

Leukaemia

Status:

Closed

Phase:

Phase 3

This trial is looking at the best way to treat acute lymphoblastic leukaemia (ALL) that is Philadelphia chromosome positive.

It is for children and young adults who have ALL that is newly diagnosed.

The trial is for children, teenagers and young adults from 1 year old and up to and including 21 years of age. We use the term ‘you’ in this summary, but if you are a parent, we are referring to your child.

Cancer Research UK supports this trial.

More about this trial

The Philadelphia chromosome Open a glossary item is a gene change (mutation) that happens in the leukaemia cells. It is quite common in adults with acute lymphoblastic leukaemia. It is rarer in children and young adults.

Read about acute lymphoblastic leukaemia in children.

Read about acute lymphoblastic leukaemia in adults.

The usual treatment for ALL that is Philadelphia chromosome positive is chemotherapy alongside imatinib. Imatinib is a type of targeted cancer drug Open a glossary item called a tyrosine kinase inhibitor. It stops signals that cancer cells use to divide and grow. After this, some people might also have a stem cell transplant .

These treatments can work well for children and young adults. But sometimes the leukaemia comes back. Researchers know that it is important to plan treatment based on the risk of the leukaemia coming back. In this trial they are looking at different ways to improve treatment based on this risk.

To begin with, everyone has initial chemotherapy and imatinib to get rid of the leukaemia (induction chemotherapy Open a glossary item ). This is standard induction treatment. The team then do some tests to work out:

how well the leukaemia has responded to treatment and
the risk of the leukaemia coming back

Depending on the results the team put you into the:

standard risk group – this is to see if it’s possible to give less intensive treatment or
high risk group – this is to see if giving imatinib after a stem cell transplant can keep the leukaemia away

The treatment you have depends on the risk group you are in.

The main aims of the trial are to find out if treating people according to risk:

improves treatment
reduces the side effects

Who can enter

The following bullet points are a summary of the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.

Who can take part

In the UK, you may be able to join this trial if all of the following apply. You:

have B cell acute lymphoblastic leukaemia (B cell ALL), T cell acute lymphoblastic leukaemia (T cell ALL) or mixed phenotypic acute leukaemia (MPAL) that has recently been diagnosed
have ALL that is Philadelphia chromosome positive
are having treatment for ALL as part of a treatment protocol. Your doctor will know this.
have started induction treatment with a standard combination of chemotherapy and imatinib
have satisfactory blood test results
are well enough to take part (performance status 0, 1 or 2). Your doctor will know more.
are willing to use reliable contraception if you are sexually active during the trial and for a period after if there is any chance you or your partner could become pregnant
were between 1 and 21 years old when you were diagnosed with ALL

Who can’t take part

You can’t take part if any of the following apply. You:

have had more than 14 days of combination treatment for ALL as part of your initial treatment (induction)
have already had more than 14 days of imatinib
have chronic myeloid leukaemia (CML)
have ALL that developed after a previous cancer that was treated with chemotherapy
have had a tyrosine kinase inhibitor such as dasatinib or a similar drug in the past. This doesn’t apply to imatinib.
have an uncontrolled infection or another medical condition that means you need ongoing treatment for low blood pressure or you need a machine to help you breathe (a mechanical ventilator)
have Down's syndrome
have a problem with how your heart beats or with the rhythm in your heart
have any other medical condition that could affect you taking part
are pregnant or breastfeeding

Trial design

This phase 3 trial is taking place in the UK, Europe and the USA. The team need 700 children and young adults to take part. This includes 18 people from the UK.

This trial involves giving:

less treatment to people with a lower risk of their leukaemia coming back
long term imatinib to people after a stem cell transplant

Standard treatment for ALL is divided into different phases (stages). The possible phases include:

induction – this aims to get rid of the leukaemia cells
intensification – this aims to stop leukaemia cells getting into the fluid around your brain and spinal cord
consolidation – this aims to stop the leukaemia coming back
maintenance treatment – this aims to stop leukaemia coming back in the long term
a small number of people need a stem cell transplant if their response to chemotherapy is not good enough

Standard induction treatment for ALL is a combination of chemotherapy and imatinib.

Induction takes about 10 weeks to complete. You then have a bone marrow test. Open a glossary item This is to find out how well the leukaemia has responded to treatment and risk of it coming back. Doctors want to see if you have leukaemia cells left behind. This is a minimal residual disease or MRD test. It is a standard test you would have even if you didn’t join the trial.

Risk groups
Depending on the results of the MRD test, you are put into a risk group:

standard risk group - this means there is no or very low levels of leukaemia remaining in the bone marrow after induction chemotherapy
high risk group – this means there are higher levels of leukaemia in the bone marrow after induction chemotherapy

The treatment you have as part of this trial depends on the risk group you are in. We have included a brief summary of each group.

The team will tell you more about the treatments you have, when you have them and for how long.

Standard risk group
You join this group if you have no or very low levels of leukaemia in the bone marrow after induction chemotherapy. Most people will fit this risk group.

This part of the trial is randomised. A computer puts you into a treatment group. Neither you nor your doctor can decide which group you go into. There are 2 groups. You have one of the following:

standard dose chemotherapy and imatinib
less intensive chemotherapy and imatinib

EsPhALL 2017 trial standard risk group randomisation diagram

The team tell you about the combinations of chemotherapy you have and how long you have each one for. Your treatment takes up to 2 years in total.

You may also need to have radiotherapy to the brain if there are leukaemia cells in the spinal cord Open a glossary item . Your doctor will talk to you about this if they think you need it. This is part of your standard treatment.

The aim of the standard risk group is to see if having less intensive chemotherapy works as well and has fewer or less severe side effects.

High risk group
You join this group if you have higher levels of leukaemia in the bone marrow after induction chemotherapy. This is compared to standard risk patients. This means you have a higher risk of the leukaemia coming back.

In this group, the standard treatment is consolidation chemotherapy and imatinib. This is followed by a stem cell transplant with someone else’s cells (an allogenic transplant Open a glossary item ).

The trial team will tell you more about having a stem cell transplant and what this involves.

The aim of the high risk group is to find out if adding long term imatinib after a stem cell transplant helps to keep the leukaemia away. 8 weeks after the transplant you restart imatinib if you are well enough. You have this for up to 10 months. This is maintenance treatment Open a glossary item . You can only have maintenance imatinib if you have a stem cell transplant.

There might not be a suitable donor or you may be unfit for a transplant. If this happens you continue with standard chemotherapy and imatinib. This is until you have completed 2 years of treatment. The team can tell you more about this.

Samples for research
You will not be asked to give any samples specifically for this trial. The researchers may use samples that you have donated to the Blood Cancer UK Cell Bank to do research for this trial. Your doctor can tell you more about this.

Hospital visits

The number of hospital visits are usually the same if you are taking part in this trial or not. Your doctor or nurse will explain how often you need to visit hospital during and after your treatment.

You have most of your treatment as an outpatient. You take some of your treatment at home.

You might also have some hospital stays. Those having a stem cell transplant have a long stay in hospital. This can be for up to 6 weeks.

During treatment you have some regular tests. These are standard tests for those having ALL treatment. These include:

As part of the trial you also have regular x-rays of your wrists to check how your bones are developing as part of the growing process.

You see the doctor regularly for check ups during treatment to see how you are getting on.

Treatment takes up to 2 years.

How you have chemotherapy
ALL treatment involves lots of different combinations of chemotherapy drugs.
You might have them as:

a tablet or liquid
a drip into a vein
into the bloodstream though a central line
an injection into a muscle
an injection into the spine, this is called intrathecal chemotherapy

Your healthcare team let you know more about the chemotherapy drugs and how long you have them for.

How you have imatinib
Imatinib is a tablet. You take it once a day, everyday. You can dissolve it in water and apple juice and drink it if you can’t swallow tablets.

The team let you know how many tablets to take. And they will let you know when to start and stop taking the tablets.

Follow up
After you finish treatment the trial team will follow you up for at least 3 years.

Side effects

The trial team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.

Some of the most common side effects of chemotherapy and imatinib include:

an increased risk of infection, bruising and bleeding or tiredness and breathlessness
skin rash, itchy peeling or red skin with blisters on the lips, eyes, skin or mouth
feeling or being sick
problems with how your liver and kidneys work
tummy (abdominal pain)
diarrhoea
numbness or tingling in your hands or feet
build up of fluid that causes swelling in your arms, hands, ankles, legs, face, eyes and other parts of the body

The trial team will let you know about all the possible side effects to look out for when you join the trial. You’ll have a chance to ask any questions you may have.

We have more information about the following treatments and their side effects: