A study looking at treatment for children and young adults with newly diagnosed acute lymphoblastic leukaemia (AllTogether-1)
Cancer type:
Status:
Phase:
This study is looking at treatment for acute lymphoblastic leukaemia (ALL). It is for children and young adults who have just been diagnosed.
Cancer Research UK supports this trial.
More about this trial
In the UK, this study is for children, teenagers and young adults up to the age of 29. We use the term 'you' in this summary, but of course if you are a parent, we are referring to your child.
The main treatment for ALL is chemotherapy. Doctors use a number of drugs in different combinations.
Chemotherapy usually works well for children and young adults with ALL. But we know from research that it is important to look at the risk of the leukaemia coming back after treatment (relapse) and plan treatment based on this risk. This means giving less treatment to people with a low risk of their leukaemia coming back. And giving more treatment to people with a higher risk of the leukaemia coming back.
Doctors use several factors to find out your risk group, these include:
gene 
changes inside the leukaemia cells- how quickly your leukaemia went away with chemotherapy
In this study, you have a combination of chemotherapy drugs based on your risk group.
The aim of this study is to see if changing , in different ways, for different risk groups:
- works better for children and young people with ALL
- reduces side effects
Who can enter
The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study if you are unsure about any of these. They will be able to advise you.
Who can take part
You may be able to join this trial if all of the following apply. You:
- have a new diagnosis of T lymphoblastic (T cell) or B lymphoblastic precursor (BCP) leukaemia (ALL). You might be able to take part if you have surface immunoglobulin negative (SIG-) BCP leukaemia with a MYC gene change unless you also have a BCL2/6 gene change. Your doctor will know more.
- have had your diagnosis confirmed at one of the specialist hospitals taking part in the study
- will be having treatment at the one of the specialist hospitals taking part in the study
- are a permanent resident of a country taking part, or be intending to settle (as this is an international study).You might be able to take part if you intend to stay for all of your treatment and have not had any treatment elsewhere.
- are generally well enough to have the study treatments
- are willing to use reliable contraception throughout the study if there is a chance you or your partner could become pregnant – your doctor can confirm suitable contraception for you, depending on your individual circumstances
- are between 1 and 29 years old
Who can’t take part
You cannot join this study if any of these apply. You:
- have had cancer before
- have ALL that has come back after treatment (relapsed ALL)
- have mature B cell ALL
- have ALL that is
Philadelphia chromosome positive - have genetic changes that might mean you are more likely to develop ALL, such as
Li-Fraumani syndrome or changes in the ETV6 gene – your doctor can let you know more about these. You might still be able to take part if you have Down’s syndrome - have had treatment for your leukaemia already - either
systemic treatment with steroids for more than 7 days or other anti cancer drugs in the 4 weeks before you were diagnosed - have any other medical condition that the researchers think would stop you from being able to take part – your doctor can explain more
- are pregnant or breastfeeding
There are more entry conditions for different parts of the study. Your doctor will explain more about these.
Trial design
This is a large, international study for people in the UK and Europe. The researchers hope that around 8,000 children and young adults will take part, including around 2,100 from the UK.
It is too complicated to go into detail on this summary, but below is an outline of the study. Your doctor will be able to tell you more about it.
At first, everyone on the trial will have standard treatment. This is a combination of chemotherapy drugs and steroids.
The trial team will ask for your permission to look at samples to see:
- what your leukaemia cells look like when you were diagnosed
- how your leukaemia is responding to treatment
They also record information about any side effects that you are having.
Treatment stages
There are 6 treatment stages.
The first stage, or block, is called induction. The aim is to get rid of the leukaemia. The three consolidation stages (stage 2, 3 and 5) aim to destroy any remaining leukaemia cells. They also stop the cancer from spreading to the brain and spinal cord.
The 4th stage is delayed intensification. It is a combination of the induction and consolidation stages. You have this to destroy any remaining cancer cells that may still be there, but they don’t show up in tests.
The final stage is called maintenance. It reduces the risk of cancer coming back after treatment is finished.
In each stage you have a combination of several chemotherapy drugs and steroids.
Risk treatment groups
The researchers look at a number of factors to work out your treatment risk group. They look at tests from:
- when you were diagnosed
- after the first stage of treatment (induction)
- after the second stage of treatment (consolidation 1)
So, after consolidation 1 your team will let you know your risk group for the rest of your treatment.
The groups are called:
- standard risk
- intermediate risk-low
- intermediate risk-high
- high risk
It depends on your risk group as to:
- how much chemotherapy you have
- how strong the chemotherapy treatment is
To help find out what treatment works best for each risk group, some parts of the study are randomised. The people taking part will be put into groups by a computer. Neither you nor your doctor will be able to decide which group you are in.
Your doctor will talk to you about the randomisations when they are due to happen.
Standard risk group (Randomisation 1)
This is one of the groups that the trial team think might benefit from less treatment. It is for people under the age of 16.
The researchers are looking at taking away doxorubicin from delayed intensification. Doxorubicin is a type of chemotherapy drug called an anthracycline.
You are put into a treatment group at random. You have 1 of the following:
- delayed intensification with doxorubicin
- delayed intensification without doxorubicin
The aim is to see if it is safe to reduce chemotherapy in this way.
Intermediate risk-low group (Randomisation 2)
The trial team think people in this group might benefit from less treatment. It is for people under the age of 16.
The researchers are looking at taking away either doxorubicin in delayed intensification or vincristine and dexamethasone in maintenance.
Vincristine is a chemotherapy drug and dexamethasone a steroid. In standard ALL treatment you have vincristine monthly and dexamethasone tablets at the same time for a few days. Doctors call these short blocks ‘pulses’.
You are put into a treatment group at random. You have 1 of the following:
- Group A - you have delayed intensification with doxorubicin. And maintenance with vincristine and dexamethasone pulses. This is standard treatment.
- Group B - you have delayed intensification without doxorubicin. And then maintenance with vincristine and dexamethasone pulses.
- Group C - you have delayed intensification with doxorubicin. And then maintenance without vincristine and dexamethasone pulses.
The aim is to see if it is safe to reduce chemotherapy in this way.
Intermediate risk-high (Randomisation 3)
This part of the study is for people who have precursor B ALL.
This is for people that researchers think might benefit from more treatment.
The researchers are looking at adding inotuzumab ozogamicin to maintenance treatment. Inotuzumab ozogamicin is a type of targeted cancer drug called a monoclonal antibody (MAB). It finds the leukaemia cells by targeting a certain protein on them. This protein is called CD22.
Everyone taking part is put into a treatment group at random.
You have either:
- maintenance as standard treatment
- treatment with inotuzumab ozogamicin for 6 weeks before maintenance
Other changes to treatment
The researchers are making other changes to treatment in the study. These changes are not randomised. The aim of these changes are to try and improve treatment by adding newer drugs, or newer ways of treating leukaemia, to standard treatment.
They include:
Imatinib
You might have a drug called imatinib if you have a change in the BCR-ABL gene. Imatinib is a type of cancer growth blocker called a tyrosine kinase inhibitor (TKI). Tyrosine kinases are proteins that cells use to signal to each other to grow.
Neralabine
You might have neralabine if you have high risk T-cell ALL.
Nelarabine is a chemotherapy drug.
Blinatumomab for people with Down's syndrome
You might have a drug called blinatumomab if you have Down’s syndrome and are in the intermediate risk or high risk group. Blinatumomab is a type of targeted cancer drug called a monoclonal antibody. It works by targeting a certain protein on the leukaemia cells so your immune system can recognise them. The immune system can then attack and kill the leukaemia cells.
CAR-T therapy
People with high risk ALL might need a lot of chemotherapy and sometimes a stem cell transplant to get their leukaemia under control.
Scientists would like to find new ways of treating high risk ALL, which are safe and work well. One potential new treatment is CAR-T cell therapy.
The study researchers are interested in finding people with high risk ALL who are able to join a different CAR-T study.
Your doctor will talk to you about different treatment options if CAR-T therapy is not available to you.
Quality of life study
The trial team would like to find out more about your . You will be asked to fill in questionnaires about how you are feeling physically and emotionally. The questionnaires are sent to your email address. Or, they are sent to parents and carers with young children taking part. This will only be done with your permission.
You don’t need to take part in this. If you say no, you can still take part in the main study.
Samples for research
Blood samples
During part of the study, you give extra blood samples. You give the samples at the same time as your usual blood tests.
Researchers use them to see if a drug called pegylated-asparaginase is working properly. Your doctors can change your treatment if the results show it is not working well.
Samples to store (Blood Cancer UK Cell Bank)
The researchers ask for small extra samples of:
- bone marrow
cerebrospinal fluid - blood
The trial team would like to collect these when you are diagnosed and up to three times during treatment. You give these samples at the same time as you have routine tests. They are stored at the Blood Cancer UK Cell Bank.
Scientists would like to use these samples to:
- learn more about why people might develop leukaemia
- improve treatment for people in the future
- reduce side effects of leukaemia treatment
You don’t have to give these samples if you don’t want to. You can still take part in the study.
Hospital visits
You have most of your treatment for ALL as an outpatient, but you will be in and out of hospital for treatment regularly. It is likely you will need to stay in hospital at times. This is usually the same if you are taking part in the study or not.
There are a few more inpatient visits than standard treatment if you have Down's syndrome and are having blinatumomab. You are likely to stay in hospital for the first few days of each .
Treatment lasts around 2 years.
You have regular lumbar puncture tests, bone marrow tests and blood tests. These are to check:
- how your leukaemia is responding to treatment
- how your body is coping with treatment
You also have other tests such as a heart trace () and heart scan ().
Having chemotherapy
ALL treatment involves lots of different chemotherapy and drugs.
You might have them as:
- a tablet or liquid
- a drip into a vein
- an injection into a muscle
- an injection into the spine, this is called
intrathecal chemotherapy
Your hospital care team will let you know:
- how often you have each drug
- how long each drip takes
- when to stop taking any chemotherapy
Follow up
After treatment has finished, the trial team will monitor you for another 3 years.
Side effects
The study 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.
You have many different chemotherapy drugs as part of this study and ALL treatment.
In general, the most common side effects of chemotherapy are:
- a drop in blood cells causing an increased risk of infection, bleeding and bruising problems, tiredness and shortness of breath
- feeling or being sick
- hair loss
- loss of appetite
- diarrhoea or constipation
- sore mouth
Some people taking part might have the immunotherapy drugs inotuzumab ozogamicin or blinatumomab.
These can affect the immune system. They may cause inflammation in different parts of the body. This can cause serious side effects. They could happen during treatment, or some months after treatment has finished. Rarely, these side effects could be life threatening.
If you have any of these side effects tell your doctor or nurse as soon as possible. You should tell them that you are on or have been on an immunotherapy.
We have more information on:
You might have imatinib. Imatinib is a type of cancer growth blocker called a tyrosine kinase inhibitor (TKI). Tyrosine kinases are proteins that cells use to signal to each other to grow.
The main side effects of imatinib include:
- increased risk of getting an infection
- breathlessness and looking pale
- bruising, bleeding gums or nosebleeds
- fluid build-up (oedema)
- skin rash
Your doctor will talk to you about the possible side effects before you agree to take part in this study.
Location
Recruitment start:
Recruitment end:
How to join a clinical trial
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Chief Investigator
Dr John Moppett
Supported by
Cancer Research UK
CRUK and UCL Cancer Trials Centre
Karolinska University Hospital
The Swedish Childhood Cancer Foundation
Servier
Other information
Cancer Research UK trial number CRUK/18/007.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
