A trial looking at improving treatment for children and young people with Langerhans cell histiocytosis (LCH-IV)

This is an international phase 3 trial. It will recruit 1,400 children and young people into group 1.

Some parts of the trial, for some groups, are randomised. Those taking part are 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 and when they are due to happen.

Group 1 

This group is for children and young people having first line treatment. First line treatment is the first treatment you have for LCH.

 Everyone in group 1 is split into two groups:

• multisystem LCH - there is LCH in more than one organ in your body
• single system LCH - to be in this group the LCH is affecting a bone in your face or more than one bone in your body. You might hear other, more general definitions of single system LCH

The first treatment for everyone in group 1 is the chemotherapy drug vinblastine and the steroid drug prednisolone. 

Multisystem LCH

The researchers are looking at:

• adding a chemotherapy drug called mercaptopurine after your course of initial treatment for LCH
• comparing treatment for 12 months with treatment for 24 months

Single system LCH

The researchers are looking at comparing 6 months of treatment with 12 months of treatment. Enough people have joined the trial in this group. So now everyone in group 1 with single system LCH has standard treatment . This is treatment for 6 months.

LCH-IV- Randomisation

You can’t join group 1 if you:

• have no active signs of LCH but have permanent problems from LCH such as a bone fracture in your spine (vertebra planar) or scarring and stiffness of your lungs (lung fibrosis)
• have had oral treatment or treatment into a vein (intravenously) for LCH before, apart from steroids for up to 7 days 
• are pregnant or breastfeeding

You may be able to join another group and take part in the trial, if you can’t take part in group 1.

Group 2 - Please note this group is now closed

This group is for children and young people who need to have second line treatment for their LCH. This means you have had first line treatment for LCH and either:

• your LCH is not getting better with treatment
• your LCH has come back

Everyone in this group will have 24 weeks of treatment with the drugs:

• vincristine
• prednisolone
• cytarabine

You go on to have more treatment, if your LCH is improving. The researchers want to look at the difference between continuing treatment with the chemotherapy drugs:

• indometacin or 
• mercaptopurine and methotrexate

Group 3

This group is for children and young people who need to have more intensive treatment.

This is because the LCH is in ‘high - risk’ organs and the LCH hasn’t got better with their first treatment. So, they are having problems which can be severe. The problems will depend on which organs the LCH is affecting. 

The researchers are looking at how well the combination of the chemotherapy drugs cytarabine and cladribine work for this group.

Group 4

This group is for children and young people who need to have further intensive treatment for their LCH. And their doctor thinks a stem cell transplant is the best treatment option for them.

The trial team want to find out:

• how safe a stem cell transplant is for this group
• how well the treatment works
• what the side effects are

Group 5

Group 5 is for children and young people who have LCH that is affecting their central nervous system (CNS). Doctors might call this CNS- LCH. There is also no LCH in any other parts of the body.

The LCH in this case can be:

• a tumour
• neurodegenerative - the LCH starts to affect the brain, this usually makes movement more difficult for children

LCH as a tumour 

The trial team are looking at how well the chemotherapy drug cladribine works for this group.

Neurodegenerative CNS LCH

The trial team are looking at how well the chemotherapy drug cytarabine works for this group.

Group 6

This group is for children and young people who have a new diagnosis of single system LCH. 

The trial team are interested in looking at how well children and young people do in this group if they have:

• no treatment - also known as the ‘watch and wait’ approach
• local treatment - such as surgery, steroid cream or a steroid injection into the area where the LCH is

Group 7

Everyone who has had treatment in this trial can join group 7. The researchers want to find out:

• the long-term effects of having LCH and LCH treatments
• if the LCH comes back after treatment.

The trial team want to follow up the children and young people for as long as possible. This is to help LCH treatment in the future.

Samples

The trial team will ask if you would be happy for a tissue sample of LCH to be stored for future research into LCH. 

Your doctor takes this sample at the same time as the biopsy which they use to confirm the LCH diagnosis.

You do not have to agree to this if you don’t want to. Your care will not be affected in any way.

Biology study

The trial team will ask you if you would be happy to give extra samples of:

• blood
• urine
• bone marrow

And part of the sample from your biopsy, if you had one at diagnosis.

You usually won’t have any extra procedures to give these samples. The trial team will let you know if an extra procedure needed.

The researchers hope that information they get from these samples will help children with LCH in the future.