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:

Blood cancers

Myeloma

Status:

Closed

Phase:

Phase 3

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 targeted drug Open a glossary item 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

ITHACA trial randomisation diagram

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 cycle of treatment Open a glossary item . 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 antihistamine Open a glossary item 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 bone marrow tests Open a glossary item .

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 stem cells. Open a glossary item

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: