MUK Eight
Research type
Research Study
Full title
A randomised phase II trial of Cyclophosphamide and Dexamethasone in combination with Ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenolidomide and bortezomib.
IRAS ID
167060
Contact name
Debbie Sherratt
Contact email
Sponsor organisation
University of Leeds
Eudract number
2014-004511-36
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Current treatment for relapsed refractory multiple myeloma is the use of cyclophosphamide and dexamethasone, often given with a third drug (e.g. thalidomide, lenalidomide or bortezimib). The combination of conventional and novel agents have provided benefits in both overall survival and progression free survival however many patients develop resistance and relapse. Thus there is a need for novel agents for these patients.
The development of ixazomib, a proteasome 20S inhibitor, provides the opportunity to increase anti-tumour activity against a wider range of tumour types. Early phase I trials and clinical experience with ixazomib suggest it has anti-tumour activity in heavily pre-treated multiple myeloma patients with durable responses/disease control. Additionally its emerging safety profile indicates ixazomib is generally well tolerated.
Cyclophosphamide and dexamethasone are both predominantly used in the treatment of multiple myeloma and for patients with RRMM who have relapsed after bortezomib and lenalidomide. Therefore evaluation of ixazomib in combination with cyclophosphamide and dexamethasone is the most valuable and practical option for patients.
Although no phase I trials have been completed with ixazomib in combination with cyclophosphamide and dexamethasone safety data from previous combinations with proteasome inhibitors phase I studies are available.
This trial is therefore designed to compare the activity of ixazomib with cyclophosphamide and dexamethasone (ICD) to that of the cyclophosphamide and dexamethasone in patients with refractory or relapsed multiple myeloma.Lay summary of study results: Link to Lay summary published on Cancer Research UK: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.cancerresearchuk.org%252Fabout-cancer%252Ffind-a-clinical-trial%252Fa-trial-of-cyclophosphamide-dexamethasone-and-ixazomib-for-myeloma-muk-8%2523undefined%2FNBTI%2F-DTCAQ%2FAQ%2Fab746474-008b-40f6-b1ed-a65709f3c1bd%2F1%2FhtxpYaiMo6%23undefined&data=05%7C02%7Cliverpoolcentral.rec%40hra.nhs.uk%7C869a70da9c24468237cf08de41416ae6%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639019946398548889%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=hrfnxaN%2Bt3lb6vZ8On8xsUroGoqeCRYdfDnjoo1iD58%3D&reserved=0
The research team found that having ixazomib with cyclophosphamide and dexamethasone did not help stop myeloma coming back. This was for people who had already had treatment for their myeloma.
Results
The research team hoped that about 250 people would join this trial. But they found it harder than they expected to find people to take part in this trial. So it closed earlier than planned.
A total of 112 people joined the trial. A computer put people taking part into 1 of 2 groups at random. There were
• 58 people in the ixazomib, cyclophosphamide and dexamethasone (ICD) group
• 54 people in the cyclophosphamide and dexamethasone (CD) group
A total of 110 people had treatment as part of this trial. The research team analysed the results in 2019.
They looked at how many people’s myeloma had got a bit better. They found it was:
• 24 out of 57 people (42%) who had ICD
• 21 out of 53 people (40%) who had CD
The also looked how long it was before people’s myeloma started to get worse. They found this was:
• 5.6 months for those who had ICD
• 6.7 months for those who had CD
They looked at the time until half the people in each group were living. They call this median overall survival. They found it was:
• about 14 months for those who had ICD
• about 19 months for those who had CD
The results for the two groups look different, but there is not a big enough difference to say for sure that it’s due to the treatment. It could be due to chance.
Quality of life
The researchers also looked at the quality of life of people taking part. They asked people to complete questionnaires at regular times during treatment. These asked how people were feeling and about any problems they were having.
They found that the quality of life in the two groups was similar at the start of the trial and at 3 months.
At 6 months, people in the CD group had a slightly higher quality of life compared to those in the ICD group.
Side effects
Most people (98%) who took part had at least one side effect from treatment. But many were mild or didn’t last long.
The most common side effects were:
• a drop in red blood cells causing shortness of breath and tiredness
• a drop in blood clotting cells (platelets) causing bruising or bleeding problems
• severe tiredness (fatigue)
• diarrhoea
• a drop in white blood cells causing an increased risk of infection
• infection
Some people had more severe side effects. This was:
• 34 people (60%) who had ICD
• 26 people (49%) who had CD
More people who had ICD had:
• a drop in white blood cells causing an increased risk of infection
• diarrhoea
• nerve changes in their hands and feet such as numbness or pins and needles
• extreme tiredness (fatigue)
• infection
• a drop in blood clotting cells (platelets) causing bruising or bleeding
More people who had CD had:
• low blood pressure
• high blood sugar
• a drop in red blood cells causing shortness of breath and tiredness
Some people decided to stop treatment because of side effects they were having. This was:
• 8 people in the ICD group
• 5 people in the CD group
Three people who had ICD died because of side effects from treatment. Two people had a serious infection. And one had bleeding in the brain. No one who had CD died because of side effects from treatment.
Conclusion
The trial team concluded that ixazomib, cyclophosphamide and dexamethasone did not work better than cyclophosphamide and dexamethasone. This is for people who’d already had treatment for their myeloma but it had come back.
People who took part in the trial were generally older, and were in frail health. One possible reason ICD didn’t work better than CD is that it may have been too harsh or caused too many side effects for the frail patients in the study.
Sometimes trials show a different combination of treatment isn’t useful for a particular type or stage of cancer. But these trials still add to our knowledge and understanding of cancer and how to treat it.REC name
North West - Liverpool Central Research Ethics Committee
REC reference
15/NW/0416
Date of REC Opinion
5 Jun 2015
REC opinion
Further Information Favourable Opinion