A study of AUTO2 for myeloma (APRIL)

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 1/2

This study is for people whose myeloma has come back or continued to get worse after having at least 2 or 3 different types of standard treatment.

Standard treatment for myeloma includes:

chemotherapy
targeted cancer drugs (biological therapy)
steroids

More about this trial

AUTO2 treatment is a CAR T cell immunotherapy. It uses white blood cells called T cells Open a glossary item

. These cells are a part of your immune system Open a glossary item

. T cells are very good at fighting infection but not so good at recognising and attacking cancer cells.

Your own T cells are used to make the AUTO2 treatment in the manufacturing unit. Two genes are introduced into your T cells. The 1st gene changes the T cells so they can recognise and attack myeloma cells.

The 2nd gene is a safety switch. When you have the AUTO2 treatment you might have side effects. The safety switch can stop the AUTO2 treatment from working if these side effects are very bad. You have a short dose of a drug called rituximab to turn this switch on. This will then stop the AUTO2 working.

To get the T cells you have a procedure called leukapheresis. This means that some of your white cells are taken from your blood stream.

Before having the AUTO2 treatment you have a short period of chemotherapy. This is called ‘pre conditioning’.

You then have the AUTO2 treatment as a drip into a vein (intravenous infusion Open a glossary item

The aims of this study are to find:

the best safe dose of AUTO2 to give
what the side effects are
how safe it is
how well it works for myeloma

Who can enter

The following bullet points list the entry conditions for this study. Talk to your doctor or the study 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 study if all of the following apply:

you have myeloma that can be measured with a blood test or urine test
your myeloma has come back or continued to grow after at least 3 different types of treatment including a targeted cancer drug, such as bortezomib or carfilzomib and an immunotherapy, such as thalidomide, lenalidomide or pomalidomide or you have had both a targeted drug and immunotherapy and your myeloma continued to get worse within 2 months
you are able to do everything apart from heavy physical work (performance status 0 or 1)
you weigh more than 30kg (4 stone)
you have satisfactory blood test results
you are willing to use 2 types of reliable contraception during the study and for at least a year afterwards if you or your partner could become pregnant and you must also agree not to donate your eggs or sperm during the study and for at least a year afterwards
you are at least 18 years old

Who can’t take part

You cannot join this study if any of these apply.

Cancer related

You:

have myeloma that has spread to your brain or spinal cord and is causing symptoms
have previously been diagnosed with systemic light chain amyloidosis
have had a donor (allogenic ) stem cell transplant
have had anti myeloma treatment within the 7 days before your pre conditioning treatment or leukapheresis
have had radiotherapy within 7 days of pre conditioning treatment or leukapheresis apart from radiotherapy to a single local area for example for bone pain
have had another cancer apart from treated in situ carcinoma of the cervix, successfully treated non melanoma skin cancer or any other cancer that has been successfully treated and there hasn’t been any sign of it in the past 2 years and there is a very small risk of it coming back
aren’t able to have cyclophosphamide, fludarabine, albumin or dimethyl sulfoxide (DMSO)
have already had gene therapy or other cell therapy treatment
have had rituximab or a similar drug within the 3 months before having AUTO2 treatment

Other medical conditions

You have:

a heart problem such as angina, heart failure or arrhythmias that isn’t controlled by medication
had a heart attack in the past 6 months
heart problems so it isn’t working well enough
had a stroke in the past 3 months
high blood pressure that isn’t controlled by medication
high blood pressure that has affected other body organs or has caused headaches
had blood clots (DVTs) or a blood clot on the lung and you are taking medication to prevent further blood clots such as warfarin
bleeding from your gut
had major surgery in the past 3 months
liver problems
kidney problems and need to have dialysis
an infection or a virus that needs treatment
HIV, hepatitis B, hepatitis C, HTLV 1, HTLV 2 or syphilis
an autoimmune disease and you take medication that affects your immune system

Other

You:

are taking more than 5mg of prednisolone daily or an equal dose of another steroid that can’t be stopped
have any other medical or mental health condition that your doctor thinks could affect you taking part in the study
are pregnant or breastfeeding

Trial design

This is a phase 1/2 study. The researchers need 80 people to join. Everyone who is able to will have AUTO2 treatment.

The 2 parts of the study

There are 2 parts to this study. Your doctor will tell you which part you are in when you agree to take part.

Part 1 is a dose escalation study. This is to find the best safe dose of AUTO2 to give. The researchers are looking at 5 doses.

The first few people will have the lowest dose. If they don’t have any bad side effects the next few people will have the next dose. If they don’t have any bad side effects the next few will have the highest dose.

Part 2 is a dose expansion study. The researchers use the best safe dose of AUTO2 from part 1.

About the AUTO2 treatment

The AUTO2 treatment is made in the manufacturing unit using a particular type of white blood cell called T cells. These are your own T cells that they collect (remove) from your blood during a process called leukapheresis.

Leukapheresis

They take the blood from your vein and put it through a machine. The machine separates the T cells from the blood. They remove the T cells and give the rest of your blood back into your bloodstream. You have this up to 3 months before the AUTO2 treatment.

Your chemotherapy and AUTO2 treatment might be delayed if any of the following happen after the leukapheresis:

you have a severe infection when you are due to have treatment
you need to have oxygen
you have pus, blood or similar substances in your lungs when you are due to have treatment
your liver or kidneys aren’t working well enough

Chemotherapy

You go in to hospital to have low dose chemotherapy. The chemotherapy helps the AUTO2 treatment survive and grow in your body.

The chemotherapy drugs you have are cyclophosphamide and fludarabine. You have both drugs as a drip into your bloodstream. Each one takes about 30 minutes to have. You have them once a day for 3 days before having the AUTO2 treatment.

AUTO2

You have the AUTO2 treatment between 3 and 5 days after the chemotherapy. You have it as drip into a vein within 30 minutes. You usually have it as a single dose.

Sometimes they can't make the AUTO2 treatment because there weren’t enough white blood cells.

Your doctor will talk to you about what other treatments are available if this happens.

Hospital visits

You go see the doctor to have some tests before taking part. These tests include:

a physical examination
blood tests
heart trace (ECG )
heart scan (MUGA or ECHO )
CT scan or PET-CT scan or MRI scan
urine test (24 hour urine collection)
bone marrow test

You go to the hospital to have leukapheresis up to 3 months before the AUTO2 treatment. You have this as a day case. You see the doctor before having it to see how you are and for:

a physical examination
blood tests

You go into hospital to have the chemotherapy and AUTO2 treatment. Before the chemotherapy, you have:

blood tests
a physical examination
24 hour urine collection
bone marrow test

You have the AUTO2 treatment 3 to 5 days after finishing the chemotherapy. Before your AUTO2 treatment you have:

a physical examination
blood tests
24 hour urine collection

During your stay in hospital, you have regular blood tests and physical examinations to see how you are after treatment. Your doctor will decide how long you need to be in hospital, which could be for 10 days or more.

After treatment, you see the doctor every week for a month:

to see how you are
for blood tests
a physical examination

A month after treatment you have:

a physical examination
blood tests
24 hour urine collection
heart trace (ECG)
bone marrow test

You then see the doctor regularly up to 2 years for the same tests apart from the heart trace.

You have a bone marrow test at:

3 months
6 months
12 months
18 months
24 months

Side effects

Leukapheresis is a safe procedure and most people don’t have side effects. Side effects might include:

feeling lightheaded
a drop in the level of calcium in your blood causing numbness and tingling particularly in the hands, feet and around the mouth. It can also cause muscle spams

Your doctor will treat the drop in calcium if it happens.

This study is the first time the AUTO2 treatment has been used in people. So, there might be side effects we don’t know about yet.

You might get side effects when you are having AUTO2. These can include:

high temperature (fever)
shivering
difficulty breathing and wheezing
rash

Your doctor can give you treatment to relieve the side effects if this happens. For example, you might have paracetamol and, or an anti histamine.

Another possible side effect is called cytokine release syndrome (CRS). AUTO2 treatment 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:

high temperature
aching muscles
low blood pressure
difficulty breathing

Other possible side effects can include:

confusion
difficulty speaking
difficulty writing
decreased alertness
fits
a drop in blood cells making you at an increased risk of getting an infection, feeling tired, bruising and bleeding
an increased risk of developing another cancer and other blood conditions

An ingredient of the AUTO2 treatment called dimethyl sulfoxide (DMSO) might cause side effects. These can include: