A trial of a new combination of treatment for newly diagnosed high risk myeloma and plasma cell leukaemia (MUK 9 b OPTIMUM)

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 2

This trial is looking at a new combination of drugs before a stem cell transplant and long term treatment for high risk myeloma and plasma cell leukaemia.

Myeloma is a type of blood cancer that starts in the bone marrow. Plasma cell leukaemia is a very rare type of blood cancer. It is similar to myeloma as it affects the plasma cells (PCL) in the blood and bone marrow. PCL and high risk myeloma are treated in the same way. So, when we refer to myeloma in the summary, we mean both.

More about this trial

There are different types of myeloma. Doctors look at blood and bone marrow samples to work out which type you have. This trial is looking at treatment for a type called high risk myeloma. It is linked with having certain gene changes (mutations) and can be more difficult to treat.

One of the usual treatments for myeloma is a stem cell transplant using your own cells. Before and after the transplant you usually have a combination of drugs that include chemotherapy and targeted drugs such a lenalidomide or bortezomib.

This trial is looking at a new combination of 5 drugs to treat newly diagnosed myeloma. Doctors already use these drugs in various combinations to treat myeloma. But this is the first time people with high risk myeloma are having all 5 together.

The drugs they are looking at are:

bortezomib (a targeted drug)
lenalidomide (a targeted drug)
daratumumab (an immunotherapy)
dexamethasone (a steroid)
cyclophosphamide (a standard chemotherapy drug)

The main aims of the trial are to:

find out how well treatment works
learn more about the side effects
find out more about quality of life

Who can enter

You may be able to join this trial if all of the following apply.

You:

have high risk myeloma or plasma cell leukaemia as confirmed by the trial
haven’t had treatment apart from a plasma exchange to remove some of the extra proteins in the blood, radiotherapy for pain control or low dose dexamethasone
have myeloma that shows up in a blood or urine test or it doesn’t show up but you are willing to have a blood marrow test at 3 months and 6 months after treatment starts
are well enough to have intensive chemotherapy and a stem cell transplant
are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
have satisfactory blood test results
are willing to use 2 forms of reliable contraception a month before starting treatment, during treatment and for at least a month afterwards if there is any chance you or your partner could become pregnant
are at least 18 years old

Who can’t take part

You cannot join this trial if any of these apply.

Myeloma related
You:

have a collection of white blood cells called plasma cells (a plasmacytoma) growing outside your bones and you have no other symptoms of myeloma
another condition related to myeloma called amyloidosis, monoclonal gammopathy of undetermined significance (MGUS) smoldering myeloma or Waldenstrom's macroglobulinaemia
have had another cancer in the past 3 years apart from successfully treated basal cell skin cancer, squamous cell skin cancer, prostate cancer with a Gleason score of 6 or less and a stable PSA blood test result
have had daratumumab or a similar drug
have had an experimental drug as part of a clinical trial, you used an experimental device within 4 weeks of joining the trial or you are taking part in another trial

Medical conditions
You:

have a problem with your heart such as a heart attack in the last year, angina that is not well controlled, an abnormal rhythm of your heart, congestive heart failure or QTc prolongation
have a lung condition called chronic obstructive pulmonary disease (COPD), or persistent asthma in the last 2 years
have an active hepatitis B or hepatis C infection
have HIV
can’t have drugs that prevent blood clots such as heparin
have moderate to severe numbness or tingling in your hands or feet (peripheral neuropathy)
have POEMS syndrome
have had major surgery in the last 2 weeks and you haven’t fully recovered
have any other medical condition or mental health problem that your doctor thinks will affect you taking part in this trial

Other
You:

are sensitive or allergic to steroids, monoclonal antibodies or certain proteins
are allergic or can’t tolerate cyclophosphamide, lenalidomide, bortezomib, daratumumab or dexamethasone
might not be able to attend hospital visits, for example you have problems with alcohol or drugs
are pregnant or breastfeeding or planning to have a baby

Trial design

This a phase 2 trial. The trial team need 95 people to take part.

This 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)

You have:

bortezomib as an injection
lenalidomide and dexamethasone as tablets
daratumumab and cyclophosphamide as a drip into a vein

The schedule of drugs is different for each part of the trial. The trial team will tell you exactly when you have each drug and for how long.

You have treatment for about 3 years as long it is working and you can cope with the side effects. You might have treatment for longer if you have maintenance treatment. When you stop treatment, your doctor will talk to you about other treatment options.

Induction treatment
You have treatment in cycles. Each 3 week period is a cycle of treatment. In this part of the trial, you have treatment in week 1 and 2 and no treatment in week 3.

You have:

cyclophosphamide
bortezomib
lenalidomide
daratumumab
dexamethasone

You have up to 6 cycles. This takes about 6 months.

Stem cell transplant
You have your stem cells collected at the hospital. You have this in the outpatient department. The trial team will tell you more about this. You are then admitted to hospital to have high dose chemotherapy with a chemotherapy drug called melphalan. This is to kill all the myeloma cells. The following day you have a stem cell transplant with the cells they collected. You have this as a drip into a vein.

Consolidation (part 1)
You have treatment in cycles. Each 4 week period is a cycle of treatment. In this part of the trial you have:

bortezomib
lenalidomide
daratumumab
dexamethasone

You have up to 6 cycles.

Consolidation (part 2)
You have treatment in cycles. Each 4 week period is a cycle of treatment. In this part of the trial you have:

bortezomib
lenalidomide
daratumumab

You have up to 12 cycles.

Maintenance treatment
You have treatment in cycles. Each 4 week period is a cycle of treatment. You have:

lenalidomide
daratumumab

You continue treatment until your myeloma gets worse.

Quality of life
The researchers will ask you to fill out a questionnaire before starting treatment, at set times during the trial and after finishing treatment. The questionnaire will ask about any side effects you have had and how you are feeling. We call this a quality of life study.

Research samples
The researchers will ask for a sample of your bone marrow that your doctor will take when you have a bone marrow test. You have 2 extra bone marrow samples if you take part in this trial compared to having standard treatment.

The researchers will also ask to take extra blood tests as part of this study. Where possible you have these at the same time as your routine blood tests.

The researchers will use the samples to find out how well treatment is working. They also look at genes to find out more about myeloma.

They will ask to store any leftover samples for future research. You don’t have to agree to this if you don’t want to. You can still take part in the trial.

MRI scan sub study

The trial team might ask you to have 3 extra MRI scans. This is to look at another way to monitor the myeloma. But you don't have to agree to this if you don't want to. You can still take part in the main trial.

Hospital visits

You see a doctor and have some tests before you start treatment. These include:

a physical examination
blood tests
urine tests
heart trace (ECG)

You have the above tests again during and after your treatment.

You have bortezomib, daratumumab and cyclophosphamide at the hospital in the outpatient department. Lenalidomide and dexamethasone are tablets and you take these at home. Although on certain days the trial team might ask you to take them at the hospital when you have your other treatment.

You will be in hospital for about 4 to 6 weeks to have your stem cell transplant. You will be at a high risk of infection, so you will be in a private room.

When you stop treatment, you see the trial team 3 months later for a check up. You see your doctor after that at routine hospital appointments. The trial team will check your medical notes to see how you are getting on.

Side effects

Having this combination of treatment is new so there may be side effects we don’t know about yet. The trial team will monitor you during the time you have treatment and you’ll have a phone number to call them if you are worried about anything

Some of the most common side effects of bortezomib include:

numbness or tingling in fingers or toes
headaches
pain
shingles
a high temperature (fever)
constipation or diarrhoea
loss of appetite
feeling or being sick
tiredness (fatigue)
a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness

Some of the most common side effects of lenalidomide include:

a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
tiredness (fatigue)
diarrhoea or constipation
muscle cramps
blood clots
skin rash
blurred vision
shaky hands (tremor)
numbness or tingling in fingers and toes
headaches and dizziness
feeling or being sick
swollen or painful joints
changes in blood sugar levels
mood changes
clouding of the lens of the eye (cataract)
stomach pain
difficulty sleeping
flu like symptoms
loss of appetite

Some of the most common side effects of daratumumab include:

a drop in the number of blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
a reaction to the infusion such as stuffy nose, cough, chills, feeling or being sick and rarely, breathing problems. This usually happens during or within the first few hours of treatment. The doctor will keep a close eye on you and treat any problems straight away.
blocked nose, sinus or lung infections
numbness or tingling of the hands, feet, arms or legs
headache
cough
shortness of breath
diarrhoea
feeling or being sick
muscle spasms
tiredness (fatigue)
fever
swelling of the hands, feet, arms or legs