MUK Twelve
Research type
Research Study
Full title
A randomised phase II trial of Selinexor, cyclophosphamide and prednisone vs cyclophosphamide and prednisone in relapsed or refractory multiple myeloma (RRMM) patients
IRAS ID
216867
Contact name
Martin Kaiser
Contact email
Sponsor organisation
University of Leeds
Eudract number
2017-001736-19
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Research Summary -
The new treatment being tested in this study is called Selinexor - this is a type of Selective Inhibitor of Nuclear Export (SINE) drug, which is taken orally. This will be given with cyclophosphamide and prednisone to see if this combination is effective at treating patients with relapsed and refractory multiple myeloma (RRMM). This study is part of the Myeloma UK Clinical Trial Network portfolio of prioritised multiple myeloma clinical studies. There will be up to 60 participants who will take part in this trial from hospitals throughout the UK. The aim of this trial is to compare two different combinations of drugs used to treat multiple myeloma that has relapsed after two or more treatment lines of anti-myeloma therapy. Cyclophosphamide and prednisone are both very commonly used in the treatment of multiple myeloma, and will often be given with a third drug (e.g. thalidomide, lenalidomide or bortezomib). However, there are currently few treatments available to patients who have not responded well (are refractory) to their previous treatment or who need further treatment because their myeloma has come back. This study is designed to compare a new combination of Selinexor, cyclophosphamide and prednisone, with cyclophosphamide and prednisone alone followed by SCP at disease progression.
Lay Summary -
Myeloma, also known as multiple myeloma, is a type of cancer arising from plasma cells found in the bone marrow. Plasma cells are a type of white blood cell. Myeloma affects around 24,000 people in the UK at any one time. It mainly affects those over the age of 65.
Myeloma is rare, but the number of people living with the disease is increasing. It is currently incurable, but new treatments mean more people are living for longer. This means around one third of patients are living for 10 years after diagnosis. Therefore, further research is needed to help offer more treatments to patients with myeloma. This is especially important in patients who are elderly and have already received several previous treatments for their disease as there are fewer options for treatment.
There are few options for myeloma treatments that are given orally (by mouth). To investigate oral treatments, the MUKtwelve study was developed. The main aim of the study was to determine whether the addition of Selinexor to two commonly used treatments, called cyclophosphamide and prednisolone, leads to an improved outcome for patients. All three of these drugs are given orally. In this study an improved outcome would mean that the myeloma is controlled by the treatment for a longer amount of time. Three patient and public involvement representatives with lived experience of myeloma were involved in the development of the study proposal via Myeloma UK.
Patients recruited to the study had relapsed or refractory myeloma. This means that they have received treatment for their myeloma before, but it either did not respond to treatment, or got better before getting worse again.
Participants were recruited from 15 NHS hospitals across the UK between July 2018 and June 2021 and were randomised to receive either:
• Selinexor + Cyclophosphamide + Prednisolone (SCP)
Or
• Cyclophosphamide + Prednisolone (CP)Participants that entered the study on the CP arm were permitted to move to the SCP treatment if their myeloma progressed (got worse).
65 patients were entered into the study. The average age of participants was 71 years, and over 75% had received 5 or more previous types of treatment for their myeloma. 48 participants were randomised to receive SCP and 17 were randomised to receive CP. 13 of the participants randomised to CP were moved to the SCP treatment because their disease got worse while being treated with CP.
During the study, participants experienced a range of side effects. The most common side effects seen were anaemia (low iron levels in the blood), neutropenia (low number of white blood cells), thrombocytopenia (low number of platelets), diarrhoea, fatigue, and nausea. A higher proportion of participants experienced these side effects in the SCP arm compared to the CP arm. Infections and renal and urinary disorders were the most common serious side effects to occur.
The study found that there was no benefit to adding Selinexor to cyclophosphamide and prednisolone for this patient population. In both treatment arms, the time from being allocated a treatment to disease progression (when the myeloma has gotten worse), was 3.6 months on average.
The design of the MUKtwelve study led to the recruitment of a group of patients not usually seen in this type of clinical trial. Although the study did not deliver a successful result, it has demonstrated that it is possible to recruit patients from this population and has highlighted the need for further research in this setting.
You can learn more about MUKtwelve soon as the study is planned to be submitted for publication in a peer reviewed scientific journal at the end of 2024.
The study was manged by the Clinical Trials Research Unit at the University of Leeds as part of the UKMRA – Myeloma UK – Concept and Access Research Programme. Sponsorship was provided by the University of Leeds and funding was provided by Karyopharm. Myeloma UK were involved in supporting and publicising the trial and patient advocacy.REC name
London - Hampstead Research Ethics Committee
REC reference
17/LO/1847
Date of REC Opinion
20 Dec 2017
REC opinion
Further Information Favourable Opinion