A trial of isatuximab, lenalidomide and dexamethasone for smouldering myeloma (ITHACA)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Status:
Phase:
This trial is looking at adding isatuximab to lenalidomide and dexamethasone for myeloma. It is for people who have myeloma without symptoms. This is called smouldering myeloma.
The trial is for people with smouldering myeloma who have a high chance of developing symptoms.
More about this trial
You don’t normally have treatment straight away if you have smouldering myeloma. Doctors keep an eye on you and treat the myeloma if you develop symptoms.
Some people with smouldering myeloma have a higher chance of developing symptoms sooner. Doctors think it might be better to treat this group of people early before they develop symptoms.
Lenalidomide and dexamethasone are a combination of drugs already used to treat myeloma.
Isatuximab is a newer drug. It is a type of 
called a monoclonal antibody. These can seek out cancer cells by looking for particular proteins.
In this trial, some people have lenalidomide and dexamethasone. And some have lenalidomide, dexamethasone and isatuximab.
The main aims of the trial are to find out:
- how safe it is to have isatuximab with lenalidomide and dexamethasone
- if adding isatuximab to dexamethasone and lenalidomide works for smouldering myeloma
- how treatment affects quality of life
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
You may be able to join this trial if all of the following apply. You:
- have smouldering myeloma that was diagnosed in the last 5 years
- have a high risk that you will develop symptoms of myeloma. This means the smouldering myeloma will become symptomatic. Your doctor looks at blood and
bone marrow samples to work this out. - have satisfactory blood test results
- are up and about more than half the day, you can look after yourself but might not be able to work (performance status 0, 1 or 2)
- 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 symptoms of myeloma. The symptoms may include too much calcium in the blood, kidney problems, a drop in red blood cells (
anaemia ), broken bones or bone pain. - have amyloid light chain amyloidosis, smouldering myeloma that has a medium risk of developing symptoms, soft tissue
plasmacytoma or myeloma that has symptoms. Your doctor will know about this. - have already had treatment for smouldering myeloma or symptomatic myeloma or you are having a type of drug called
bisphosphonates , denosumab or a similar drug. Your doctor will know this. You should be able to take part if you are having bisphosphonates to treat osteoporosis. - have had treatment for another cancer in the last 3 years. You can join if you have
non melanoma skin cancer , early bladder cancer, low risk prostate cancer, or any other early cancer that was successfully treated.
Medical conditions
You cannot join this trial if any of these apply. You:
- have an infection that isn’t well controlled within 28 days of joining a treatment group
- have had a heart attack or another significant
heart problem in the last 3 months. The trial team check if you have a heart condition before you join the trial. - have had a stroke, mini stroke or a blood clot in the last 3 months
- have HIV that needs treatment, an active hepatitis A, hepatitis B or hepatitis C infection or any other severe infection that needs treatment
- have any condition that means you can’t absorb lenalidomide
- have had a recent
peptic ulcer and treatment isn’t working, inflammation of the oesophagus or stomach, inflammatory bowel disease or a digestive problem called diverticulitis - are having treatment with
steroids unless it is a low dose - agree not to donate blood during the trial and for a period of time after
- have any other medical condition or mental health problem that the trial team think could affect you taking part
Other
You cannot join this trial if any of these apply. You:
- are allergic to dexamethasone, any of the trial drugs or anything they contain
- can’t have treatment to prevent a blood clot. Your doctor will know this.
- have had a live
vaccination in the last 4 weeks - are pregnant or breastfeeding
Trial design
This phase 3 trial is taking place worldwide. The team need about 320 people to take part. There are 2 parts to this trial.
Part 1 includes 20 people. In part 1 everyone has lenalidomide, dexamethasone and isatuximab. This is to check how safe this combination of treatment is. When this part is finished then part 2 can begin.
Part 2 is randomised. The team need 300 people to take part. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in.
There are 2 treatment groups. You have one of the following:
- lenalidomide and dexamethasone
- lenalidomide, dexamethasone and isatuximab
Lenalidomide and dexamethasone
Lenalidomide is a capsule. You take it every day for 3 weeks and then you have a week of not taking it. Dexamethasone is a tablet you take once a week. You might have the first dose of dexamethasone as a drip into a vein.
Each 4 week period is called a . You have treatment for up to 2 years. You stop treatment if your myeloma gets worse.
Lenalidomide, dexamethasone and isatuximab
You have lenalidomide and dexamethasone as described above.
You have isatuximab as a drip into a vein. You have treatment in cycles. Each 4 week period is a cycle of treatment. You have isatuximab:
- once a week in the first cycle
- every two weeks from cycle 2 to cycle 12
- once a month after that
You have isatuximab for up to 3 years. You stop treatment if your smouldering myeloma gets worse.
You also have paracetamol and an a few hours before isatuximab. This is to reduce the chance of having a reaction to it.
Samples for research
The trial team ask you to give some extra blood samples. Where possible you have these at the same time as your routine blood tests. They also ask for samples from the .
The researchers plan to use the samples to:
- look at substances called
biomarkers to help work out why treatment might work for some people and not for others - look at
genes in your myeloma cells to learn more about myeloma - see what happens to isatuximab in the body
Quality of life
The trial team ask you to fill out a questionnaire:
- before you start treatment
- at set times during treatment
The questionnaire asks about side effects and how you’ve been feeling. This is called a quality of life study.
Hospital visits
You see the doctor and have tests before you can take part. These include:
- blood tests
- a
physical examination - urine test and a 24 hour urine collection
- heart trace (ECG)
- eye test
- bone marrow test
- PET-CT scan or a CT scan
- MRI scan
The doctors might also collect your
You have regular check ups during the trial. You have a PET-CT scan and an MRI scan once a year.
Follow up
When you stop treatment you have a check up:
- once a month for 3 years if your smouldering myeloma hasn’t got worse and then
- every 3 to 4 months until your smouldering myeloma gets worse
If you stopped treatment because your myeloma got worse, you have a check up every 6 months. The team can let you know how long this will be for.
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.
The most common side effects of isatuximab we know about so far include:
- a reaction during the infusion which can cause swelling of the lips, face or throat, breathing difficulties, fever and chills
- tiredness (fatigue)
- diarrhoea
- feeling or being sick
- coughs and colds (upper respiratory tract infections)
- back pain
- a drop in the number of red blood cells causing breathlessness and tiredness (
anaemia ) - headache
- loss of appetite
- high temperatures (fever)
Another possible side effect is called cytokine release syndrome (CRS). Isatuximab can cause the release of a chemical in the body called cytokines. The side effects of the release of these cytokines can be mild to severe. They can include:
- flu-like symptoms
- low blood pressure
- fast heartbeat
- difficulty breathing
- feeling sick
- headache
- kidney damage
- skin rash
- confusion
You might also develop the following:
- a breakdown of tumour cells (tumour lysis syndrome) which can cause high levels of certain chemicals in your body
- potential interference of isatuximab with blood bank tests. These are the tests you have before a
blood transfusion . Your doctor can tell you more about this. antibodies to isatuximab
The trial doctor will talk to you about all the possible side effects of treatment before you join the trial. You’ll have a chance to ask questions.
We have more information about:
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 Mamta Garg
Supported by
Sanofi
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
