A trial comparing treatments for myeloma (MRC Myeloma IX)

Who can enter

You can enter this trial if you

• Have recently been diagnosed with myeloma that is causing symptoms (symptomatic myeloma) OR
• Have myeloma that doesn’t produce enough paraprotein to be detected in a blood or urine test (non secretory multiple myeloma)
• Are prepared to use reliable contraception from 4 weeks before you start treatment, while you are taking part in the trial, and up to 4 weeks after your last dose of thalidomide
• Are prepared to have a pregnancy test every 2 to 4 weeks if there is any chance you could become pregnant
• Are at least 18 years old

You cannot enter this trial if you

• Have been diagnosed with myeloma but are not having symptoms (asymptomatic myeloma) OR
• Have been diagnosed with a solitary plasmacytoma in a bone, or plasmacytoma in another part of your body (extramedullary plasmacytoma) without evidence of myeloma
• Have had any other cancer apart from basal cell skin cancer that was successfully removed with an operation, or another carcinoma in situ
• Have had treatment for your myeloma before, apart from radiotherapy for bone pain or spinal cord compression, bisphosphonates or short term steroids
• Have acute kidney (renal) failure, and your kidney function has not improved after 3 days of being on a drip
• Have any other serious medical condition
• Are pregnant

Trial design

This trial will recruit about 1600 patients into 2 main groups. If you are young and fit enough, you will have more intensive treatment. This includes high dose chemotherapy and a stem cell transplant. But if you are older or less fit, you will have less intensive treatment which doesn’t include a stem cell transplant.

Whether you have intensive or non intensive treatment, you will be put into 1 of 4 groups by a computer. Neither you nor your doctor will be able to decide which of these 4 groups you are in. This is called randomisation, or ‘being randomised’.

Intensive treatment.

Please note - The trial finished recruiting people into the intensive treatment group in June 2007.

• Group 1 will have clodronate and CVAD chemotherapy
• Group 2 will have zoledronic acid and CVAD chemotherapy
• Group 3 will have clodronate and CTD chemotherapy
• Group 4 will have zoledronic acid and CTD chemotherapy

You have clodronate tablets every day. Or zoledronic acid though a drip once every 3 weeks while you are having treatment, and then every 4 weeks after that. You will continue to have clodronate or zoledronic acid as long as your myeloma doesn’t start to grow again and you don’t have problems with side effects.

You will have CVAD or CTD chemotherapy every 3 weeks (one cycle). You will have between 4 and 6 cycles.

One cycle of CVAD is

• Cyclophosphamide through a drip into a vein or as tablets once a week
• Vincristine and doxorubicin (Adriamycin) together as an infusion through a central line into a vein, continuously for 4 days once every 3 weeks
• Dexamethasone tablets (a steroid) for 4 days, twice in every 3 weeks

One cycle of CTD is

• Cyclophosphamide tablets once a week
• Thalidomide tablets every day
• Dexamethasone tablets for 4 days, twice in every 3 weeks

If the chemotherapy works, you will go on to have high dose melphalan and a stem cell transplant regardless of which group you are in. If the chemotherapy doesn’t work and your myeloma continues to grow, you will not go on to have a stem cell transplant. Your doctor will discuss other treatment options with you. If your myeloma remains the same during chemotherapy, you may have a stem cell transplant but you may not. The doctors will decide what is best for each individual patient.

About 6 weeks after your stem cell transplant you will be randomised again. This time either to have thalidomide as maintenance therapy, or to have no maintenance therapy. If you are in the group that have thalidomide, you will take it every day as long as your myeloma doesn’t come back and you don’t have problems with side effects.

If you have a brother or sister that is a ‘match’ and you are fit enough, you may have a transplant using their stem cells (an allogeneic transplant) after having a transplant using your own cells (an autologous transplant). You will have lower doses of chemotherapy for this allogeneic transplant. This new approach is called a ‘low intensity conditioning allogeneic stem cell transplant’, or a ‘non myeloablative’ transplant. If you have this, you will not go on to have thalidomide maintenance therapy. Your doctors will discuss this with you in more detail.

Non intensive treatment.

• Group 1 will have clodronate and MP chemotherapy
• Group 2 will have zoledronic acid and MP chemotherapy
• Group 3 will have clodronate and CTDa chemotherapy
• Group 4 will have zoledronic acid and CTDa chemotherapy

You have clodronate tablets every day. Or zoledronic acid though a drip once every 4 weeks. You will continue to have clodronate or zoledronic acid as long as your myeloma doesn’t start to grow again and you don’t have problems with side effects.

You will have MP or CTDa chemotherapy every 4 weeks (one cycle). You will have between 6 and 9 cycles.

One cycle of MP is

• Melphalan tablets once a day for 4 days every 4 weeks
• Prednisolone tablets (a steroid) once a day for the same 4 days, once every 4 weeks

One cycle of CTDa is

• Cyclophosphamide tablets once a week
• Thalidomide tablets every day (starting at a lower dose than in CTD)
• Dexamethasone tablets for 4 days, twice in every 4 weeks (a lower dose than in CTD)

If the treatment works well, you will then be randomised again to either have thalidomide as maintenance therapy or not. If you are in the thalidomide group, you will take it every day for as long as your myeloma doesn’t come back and you don’t have problems with side effects.

If the chemotherapy has not worked well, you will not go on to have maintenance therapy. Your doctors will discuss other treatment options with you.

All patients.

The research team will ask you to fill out a questionnaire before you have treatment, then 3 months, 6 months and a year after you have treatment, and every year after that. It will ask you how you have been feeling and about any side effects you are having. This is called a Quality of Life questionnaire. You will also fill out a ‘diary card’ every day for the first 3 months of your treatment. But you don’t have to agree to do this part of the trial.

The team will also ask you if they can look at samples of your blood, bone marrow and urine in the lab. You don’t have to agree to do this part of the trial. You can still take part in rest of the trial, even if you prefer not to take part in these 2 parts.

If at any point during or after your treatment, your cancer comes back or starts to go grow again, your doctor will discuss other treatment options with you.

Hospital visits

You will have some tests before you start the trial. These will include

• Blood tests
• Urine tests
• Bone marrow biopsy
• X-rays of your spine, head, chest, pelvis and shoulders

You may also have an MRI scan or CT scan.

You will go to hospital to have chemotherapy as an outpatient. If you have vincristine and doxorubicin for 4 days, you can have this at home. You will have the chemotherapy via a small pump attached to your central line. You will go back to the hospital 4 days later to have the pump removed.

If you are in the intensive group, you will have chemotherapy every 3 weeks for up to 5 months. If you are in the non intensive group, you will have chemotherapy every 4 weeks for about 9 months.

If you have the intensive treatment you will also have high dose melphalan and a stem cell transplant. You will be in hospital for several weeks while you have this.

If you have thalidomide you will see the doctors every 4 weeks. You will have to answer some pre recorded questions using a voice recognition system on the phone before the doctors give you the next 4 weeks supply. Unless you are a woman who has been through the menopause or had a hysterectomy, in which case you will only have the telephone interview every 6 months. Women able to have children will also have a pregnancy test every 2 to 4 weeks.

After you finish treatment you will see the doctors at least every 3 months. You will have blood tests at each visit, and an X-ray and bone marrow test once a year.

Side effects

The most common side effects of the chemotherapy drugs used in this trial are

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

The side effects of thalidomide include

• Constipation
• Weakness
• Numbness and tingling in your hands and feet (peripheral neuropathy)
• Dizziness
• Skin rash
• Sickness
• Headache

But remember, not everyone will get all these side effects. There is more information about the side effects of cyclophosphamide, vincristine, doxorubicin (Adriamycin), melphalan, and having a stem cell transplant on CancerHelp UK.

Some patients who have had bisphosphonate treatment have developed a rare condition called osteonecrosis of the jaw. This means that part of the bone in the jaw dies. No one is very sure at the moment if this is due to the bisphosphonates, other treatments or other risk factors. Although it is rare, the risk seems to be increased if you have had a tooth extraction. There is more information about osteonecrosis of the jaw in the question and answer section of CancerHelp UK.