A trial looking at a second stem cell transplant for people whose myeloma has come back following a previous transplant (Myeloma X Relapse - Intensive)

Who can enter

You can enter this trial if you

• Have myeloma that has come back (relapsed), is causing symptoms and you have already had treatment with standard chemotherapy and your own stem cells (autolologous transplant)
• Had your transplant at least 12 months ago and your doctor now recommends further treatment
• Have satisfactory blood test results
• Are well enough to take part (you have a performance status of 0, 1 or 2)
• Are at least 18 years old
• Are willing to use reliable contraception during treatment and for 6 months after treatment if there is a chance that you or your partner could become pregnant

You cannot enter this trial if you

• Have already had treatment for your relapsed myeloma (you may still be able to take part if you have had radiotherapy to treat symptoms, plasma exchange, or treatment with dexamethasone steroids)
• Have already had treatment with bortezomib, doxorubicin and dexamethasone and your myeloma was resistant to these drugs
• Peripheral neuropathy that is grade 2 or above (your doctor would be able to say if this applies to you)
• Are known to be HIV positive, have hepatitis B or hepatitis C (you will not be tested as part of this trial)
• You have taken part in another clinical trial within the last month
• Are allergic to boron or mannitol
• Are pregnant or breastfeeding
• Have had any other cancer in the past 5 years (apart from non melanoma skin cancer or cervical cancer which have been treated)

Trial design

This phase 3 trial will recruit 460 people whose myeloma has come back after a stem cell transplant.

The first part of the trial is called induction treatment, and this aims to get rid of as much of the myeloma as possible. Everyone taking part will have treatment with PAD (bortezomib, doxorubicin and dexamethasone. Before your treatment begins you may have a central or long line put in. This makes it easier to give chemotherapy and take blood samples.

You have PAD in 3 week periods called cycles of treatment. You have bortezomib as an injection into your central line if you have one, or through your vein. This will take a few minutes. You also have doxorubicin through your central line or vein, but this time through an infusion pump continuously over 4 days. On day 4 you have more bortezomib. You have dexamethasone as tablets. The nurse or doctor will explain when and how often you have each drug. You have between 2 and 4 cycles, depending on how well the treatment works. So this part of the treatment will take between 6 to 12 weeks.

There is a small chance that PAD treatment may not work. If this happens, you will not continue with treatment as part of this trial. Your hospital doctor will talk to you about further treatment.

The next part of the trial is your stem cells collection (harvest). You may not have this done if you have enough stem cells stored from when you had your first stem cell collection.

For your stem cell collection you first have daily injections of growth factor for about 7 to 10 days. You also have one treatment with cyclophosphamide chemotherapy into your central line or a vein. The growth factors and chemotherapy help to make your bone marrow produce stem cells. You then have your stem cells collected and stored.

If it is not possible to collect enough stem cells, your doctor may recommend that they try again using different drugs. There may still be a chance that you do not have enough stem cells collected in order to have a stem cell transplant. If so, your doctor will talk to you about further treatment, you will not continue treatment as part of this trial.

The final part of the trial is consolidation treatment. Its aims is to stop the cancer coming back for as long as possible. This part of the trial is randomised. This means that you are put into one of two different treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in.

If you are in group 1, you have intensive treatment with high dose chemotherapy and an autologous stem cell transplant. You have a high dose of melphalan into your central line or a vein. One day later you have your stem cell transplant.

If you are in group 2, you have low dose chemotherapy. You have cyclophosphamide tablets once a week for 12 weeks. If you have difficulty swallowing the tablets or they make you feel sick, you may have cyclophosphamide through a drip. You will still have stored stem cells and these may be used at a later date, but not as part of this trial.

Hospital visits

Before you start treatment you will have some tests to find out if you are suitable for this trial. These may include

• Blood tests
• Urine tests
• Bone marrow test
• Heart scan (echocardiogram)

You will probably have PAD treatment as a day patient visiting the hospital nearly every week.

If you are in group 1, you will be in hospital for about 3 to 4 weeks. You will be in isolation for some of this time. You will not be able to leave your room, but you can have visitors. This will be the same as when you had your first autologous stem cell transplant.

If you are in group 2, you take your tablets at home. You will visit hospital for a blood test and to see a doctor every 2 to 4 weeks. If you have cyclophosphamide through a drip you will visit hospital every week for your treatment.

As part of a ‘quality of life’ study you will also fill out a questionnaire. This will ask you how you have been feeling and about side effects. This part of the trial is optional. You do not have to agree to complete these questionanaires if you don’t want to. You will still be able to take part in the trial. If you agree, you will complete a questionnaire

• At the start of the trial
• After PAD chemotherapy
• Before randomisation
• After 3, 6 and 12 months
• Yearly after that

The trial doctors will also ask you to give extra blood and urine samples and extra bone marrow and stem cells samples. Where possible, these samples will be taken at the same time you are due to have these tests as part of your treatment. The samples will be stored to be used for research in the future. This part of the trial is optional. You do not have to agree to these extra tests if you don’t want to. You will still be able to take part in the trial.

If you do not go on to have consolidation treatment, your follow up appointments with the trial doctors will stop 3 to 4 months after you first started the trial. You will continue to see your hospital doctor and these will be arranged on an individual basis.

If you have consolidation treatment, you will have follow up appointments as part of this trial at least every 3 months. You will be examined by a doctor and have blood tests and you may have other tests. These will be arranged so that they are at the same time as your routine appointments with your hospital doctor.

Side effects

All treatments have side effects. The most common side effects of bortezomib include

• Tiredness
• Skin rash and itching
• Tummy pain with diarrhoea or constipation
• Feeling or being sick
• Weight loss
• Numbness or tingling in the hands or feet
• A drop in your blood count causing an increased risk of infection, bruising or bleeding problems and tiredness

The most common side effects of chemotherapy are

• A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
• Feeling or being sick
• Sore mouth (mucositis)
• Loss of appetite
• Diarrhoea

Earlier trials suggest that the risks associated with having a second transplant may be greater than the first. Your doctor will explain this to you in more detail.

There is more information about the particular side effects of doxorubicin, cyclophosphamide and melphalan on CancerHelp UK.