A trial looking at different combinations of treatment for newly diagnosed myeloma (RADAR, Myeloma XV)
Cancer type:
Status:
Phase:
This trial is looking at 
to help work out the best treatment for myeloma. It is also looking at measuring small amounts of myeloma cells that may be present after initial treatment. This is called .
It is for people who:
- are suitable to have a
stem cell transplant and - haven’t had treatment for myeloma
Cancer Research UK supports this trial.
More about this trial
Lenalidomide, bortezomib, dexamethasone and cyclophosphamide are all standard treatments for myeloma. They are not yet available on the NHS in the particular combinations you have in this trial. You might also have a stem cell transplant as part of your routine care.
Isatuximab is a newer treatment. Some people have it for myeloma that has come back. It isn’t yet a treatment for newly diagnosed myeloma. Isatuximab is an immunotherapy. It helps the to find and kill cancer cells. Doctors aren’t sure how well it will work for newly diagnosed myeloma.
In this trial, researchers are looking at different combinations of treatment to improve outcomes for people with myeloma. The treatment you have depends on:
- the
genetic make up of the cancer - how well initial treatment works
To work this out doctors examine and blood tests.
Those who have certain gene changes have high risk myeloma. Sometimes treatment doesn’t work as well for this group of people. Those who don’t have these changes have standard risk myeloma.
The main aims of the trial are to find out:
- how well the different combinations of treatment work for these groups
- more about the side effects
- how treatment affects quality of life
Who can enter
Please note, there are several treatment groups so the entry conditions for this trial are complex. Each group has specific entry conditions and we haven’t listed them all.
The trial team check if you are suitable to join the trial and which group you might join. They can tell you more about this.
The group you join depends on a number of factors such as:
- if you have high risk or standard risk myeloma
- how well your initial treatment works
The following bullet points summarise some of the main entry conditions. 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
You may be able to join this trial if all of the following apply. You:
- have newly diagnosed myeloma
- are suitable to have as stem cell transplant
- can swallow medication
- are well enough to be up for more than half a day but might not be able to work (performance status 0, 1 or 2)
- have satisfactory blood test results
- are willing to use reliable contraception during the trial and for a period after if there is any chance you or your partner could become pregnant
- are at least 18 years old
Who can’t take part
Cancer related
You cannot join this trial if any of these apply. You:
- have had treatment for myeloma in the past. You might be able to join if you had radiotherapy to help with bone pain or
spinal cord compression or you have had bisphosphonates or steroid treatment - have myeloma that isn't causing symptoms, monoclonal gammopathy (MGUS), a single plasmacytoma of the bone or you have plasmacytoma of the soft tissue
- have had another cancer that needed treatment in the last 5 years or has come back. You can join if you have had
non melanoma skin cancer , carcinoma in situ of the cervix or a single plasmacytoma that has been successfully treated.
Medical conditions
You cannot join this trial if any of these apply. You:
- have had a heart attack in the last 4 months or a significant
heart problem that needs treatment. The trial team check if you have a heart condition before you join the trial. - have moderate to bad numbness and tingling or pain in your hands or feet
- have had major surgery in the last 3 weeks and the trial team think this could affect you taking part. You can join if you had surgery to relieve
spinal cord compression or treatment for bone fractures. - have HIV, an active hepatitis B or hepatitis C infection or any infection that needs treatment into the bloodstream
- have a high risk of developing a blood clot. This includes taking hormone replacement therapy (
HRT ). You might be able to take part if your doctor thinks you could stop having these treatments. Or you can have extra treatment to stop this happening. - have a risk of developing seizures (fits) or you take medication but it doesn’t control them
- can’t absorb medication you take by mouth for any reason
- have any other medical condition or mental health problem that could affect you taking part
Other
You cannot join this trial if any of these apply. You:
- are pregnant or breastfeeding
- are allergic, resistant to or you can’t have any of the treatments in the trial
- have had a
live vaccine within 4 weeks of starting trial treatment, you might need one during the trial or for a period after
| As well as the above there are specific entry conditions and exclusion criteria for each treatment group. Speak to your doctor or research nurse if you want to find out more about the entry conditions for this trial. |
Trial design
This phase 2/3 trial is taking place in the UK. The team are aiming for 1,400 people to take part.
The trial involves:
- treatment to get rid of the myeloma cells (induction treatment)
- a stem cell transplant
- more treatment to lower the chances of the myeloma coming back (consolidation treatment)
- long term treatment to keep the myeloma away (maintenance treatment)
The treatment you have includes:
- bortezomib – a
targeted cancer drug - lenalidomide – a targeted cancer drug
- cyclophosphamide – a chemotherapy drug
- dexamethasone – a steroid
- some people having isatuximab – an immunotherapy
You also have melphalan chemotherapy when you have your .
The schedule of drugs is different for each part of the trial. The trial team will tell you exactly which drugs you have, when you have each drug and for how long.
Some parts of the trial are randomised. You are put into a treatment group at random. Neither you nor your doctor can decide which group you are in.
Initial Treatment
You have a bone marrow test to check to see if you have certain gene changes in your myeloma cells. People with these gene changes have high risk myeloma. People without these changes have standard risk myeloma.
Everyone then has lenalidomide, cyclophosphamide, bortezomib and dexamethasone for the first . Each cycle is 3 weeks.
Those who have standard risk myeloma have 3 more cycles of treatment with the above drugs.
Those who have high risk myeloma have 5 more cycles of treatment with the above drugs. They also have a drug called isatuximab.
You then have melphalan chemotherapy and a stem cell transplant. This is part of your routine care. Your doctor can tell you more about this treatment. They can also tell you how long you’ll be in hospital for and how long it will take to recover from the stem cell transplant.
Minimal residual disease (MRD) test
3 months after the stem cell transplant you have a bone marrow test and blood tests to see how well treatment worked. The team check if you have any myeloma cells left in your bone marrow. This is called Minimal Residual Disease or MRD.
To have further treatment, the team need to know if you:
- have myeloma cells present after the stem cell transplant. This means you are MRD positive.
- have no myeloma cells after the stem cell transplant. This means you are MRD negative.
Further treatment
The treatment you have next depends on whether you:
- have standard or high risk myeloma and
- if you are MRD negative or MRD positive
Standard risk groups
Standard risk MRD negative group (R1)
To begin with you have 12 cycles of isatuximab. Each cycle is 4 weeks. This takes about a year in total. You then have another MRD test. Those who are MRD positive continue to have isatuximab. Those who are still MRD negative are put into a treatment group at .
There are 2 treatment groups. You have one of the following:
- you continue to have isatuximab until your myeloma comes back
- you stop having isatuximab
The aim is to see if no further treatment with isatuximab works just as well as continuing to have treatment with this drug.
Standard risk MRD positive group (R2)
You are put into a treatment group at random. There are 4 groups. You have one of the following:
- lenalidomide on its own. This is
consolidation followed by maintenance treatment . It is the standard treatment . - 4
cycles of lenalidomide, bortezomib and dexamethasone. This is consolidation treatment. This is followed by long term lenalidomide (maintenance treatment). - lenalidomide and isatuximab. This is maintenance treatment.
- 4 cycles of lenalidomide, bortezomib, isatuximab and dexamethasone. This is consolidation treatment. This is followed by long term lenalidomide and isatuximab. This is maintenance treatment.
You stop treatment if your myeloma gets worse. The aim is to see which treatment works best.
High risk group
In the high risk group everyone has lenalidomide, bortezomib, isatuximab and dexamethasone. You have 24 cycles of treatment. Each cycle is 4 weeks. After 6 cycles you stop having dexamethasone and treatment continues with lenalidomide, bortezomib and isatuximab.
You then have long term lenalidomide and isatuximab. You have this for as long as treatment is working and the side effects aren’t too bad.
Quality of life
The trial team ask you to fill out questionnaires:
- before you start treatment
- at set times during treatment
- at set times after treatment
The questionnaires ask about side effects and how you’ve been feeling. This is called a quality of life study.
Samples for research
The researchers will ask to take some extra fluid when you have a bone marrow test. They will also ask to take some extra blood and urine samples. Where possible, you have the blood samples at the same time as your routine blood tests.
They plan to use the samples to:
- see how well the treatment is working
- look at
genes to understand more about myeloma - check for minimal residual disease
- study the immune function of the
bone marrow
You need to agree to give most of the samples to take part in the trial. The team may ask to use the samples for future research. You can say no to this. It won’t affect you taking part in the rest of the trial.
Hospital visits
You see the doctor and have tests before you can take part. These include:
- blood tests
- a
physical examination - heart trace (ECG)
- bone marrow test
- CT scan or MRI scan
You see the doctor for regular check ups, blood tests and bone marrow tests. How often you have these depends on which part of the trial you are in. The trial team can tell you more about this.
Treatment and how you have it
You have bortezomib as an injection under your skin. You have this at the hospital on the day care ward. It might be possible for a healthcare professional to give you the injection at home. Or you might be able to do the injection yourself. You can ask your healthcare team about this.
Lenalidomide is a capsule.
Cyclophosphamide is a tablet or capsule.
Dexamethasone is a tablet.
You have isatuximab as a drip into a vein. You have this at the hospital on the day care ward.
How often you have the above treatments depends on which part of the trial you are in. The trial team can tell you more about this.
Follow up
The team follow you up every 2 months when you finish treatment. You might see them at a routine hospital appointment or they may call you to see how you are getting on.
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.
|
Isatuximab can affect the These side effects could happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for. |
Isatuximab is a newer treatment so there might be side effects we don’t know about yet. Below are the most common side effects that people reported. It isn’t known if they are all caused by isatuximab. The side effects include:
- a reaction that can happen while you are having isatuximab or the day after. This is called an infusion reaction. Signs include a high temperature (fever), chills, shortness of breath, feeling sick (nausea) and changes in blood pressure
- tiredness (fatigue)
- feeling or being sick
- a drop in the number red blood cells (
anaemia) - cough
- colds and sore throats
- diarrhoea or constipation
- headache
- shortness of breath
- back pain
- high temperatures (fever)
- chills
- loss of appetite
- chest discomfort
- swelling of the arms and legs
- tumour lysis syndrome – this can be mild or severe. Your doctor takes blood tests regularly to check.
Your doctor will talk to you about all the possible side effects of treatment. You’ll have a chance to ask any questions you may have.
We have more information about the following treatments and their side effects:
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
Professor Kwee Yong
Dr Karthik Ramasamy
Supported by
Cancer Research UK
Celgene
Sanofi
University of Leeds
Other information
This is Cancer Research UK trial number CRUK/17/012.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
