Contact information
Type
Scientific
Primary contact
Miss Rowena Henderson
ORCID ID
Contact details
CTRU
University of Leeds
Leeds
LS2 9JT
United Kingdom
+44 (0)113 3433906
ctru-muk12@leeds.ac.uk
Additional identifiers
EudraCT number
2017-001736-19
ClinicalTrials.gov number
Protocol/serial number
36466
Study information
Scientific title
A randomised phase II trial of selinexor, cyclophosphamide and prednisone vs cyclophosphamide and prednisone in relapsed or refractory multiple myeloma (RRMM) patients
Acronym
MUK Twelve
Study hypothesis
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.
Ethics approval
London – Hampstead Research Ethics Committee, 20/12/2017, ref: 17/LO/1847
Study design
Randomised; Interventional; Design type: Treatment, Drug
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
No participant information sheet available
Condition
Relapsed or refractory multiple myeloma
Intervention
The trial is designed as a randomised, controlled, open, parallel group, multicentre phase II trial to evaluate the clinical efficacy of selinexor in combination with cyclophosphamide and prednisolone. A calibration group will receive cyclophosphamide plus prednisolone alone, and will be used to evaluate the validity of the outcome in the experimental group. Participants will be randomised on a 3:1 basis to receive either selinexor + cyclophosphamide + prednisolone (SCP) or cyclophosphamide + prednisolone (CP).
A maximum of 60 participants will be recruited (45 participants in the SCP arm, and 15 participants in the CP arm). Participants who experience disease progression on the CP arm may receive SCP, once progression has been confirmed by the CTRU and the participant has been deemed eligible to receive SCP. Patients randomised to SCP have no further trial treatment stipulated following SCP therapy. The analysis of the treatment switch phase of the trial is exploratory.
SCP combination
Selinexor oral 100mg once a week – days 1 , 8 , 15 & 22
Cyclophosphamide oral 50mg once daily, starting on day 1
Prednisolone oral 30mg every other day, starting on day 1
CP combination
Cyclophosphamide oral 50mg once daily, starting on day 1
Prednisolone oral 30mg every other day, starting on day 1
Followed by SCP Combination
Selinexor oral 100mg once a week – days 1, 8, 15 & 22
Cyclophosphamide oral 50mg (or dose given previously) once daily, starting on day 1
Prednisolone oral 30mg (or dose given previously) every other day, starting on day 1
The final analysis will take place after all patients have been followed up for at least 6 months or have progressed on the first phase of treatment (whichever is sooner). Further analyses relating to the treatment switch phase of the trial will take place after all patients have been followed up for at least 6 months or have progressed (whichever is sooner).
Intervention type
Drug
Phase
Phase II
Drug names
Selinexor
Primary outcome measure
Progression free survival at 6 months
Secondary outcome measures
1. Safety and toxicity, via adverse reactions and adverse events from consent until 28 days post last dose of trial treatment
2. Progression-free survival at 6 months or until disease progression, monitored via blood results
3. Maximum response, monitored via blood results throughout the trial
4. Time to maximum response, monitored via blood results throughout the trial
5. Duration of response, monitored via blood results throughout the trial
6. Compliance to therapy, measured at all stages of the trial
Overall trial start date
01/12/2016
Overall trial end date
01/04/2021
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Able to give informed consent and willing to follow all trial protocol assessments
2. Aged 18 years or over
3. Participants with confirmed myeloma based on International Myeloma Working Group (IMWG) criteria
4. Measurable disease with at least one of the following:
4.1. Paraprotein ≥5g/L
4.2. Serum free light chains ≥100mg/L with abnormal ratio for light chain only myeloma
4.3. Bence Jones protein ≥200mg/24h
5. Participants with relapsed or relapsed refractory myeloma who have received ≥ 2 prior anti-myeloma treatments including a proteasome inhibitor and lenalidomide, and now require further treatment
6. Patients for which cyclophosphamide and prednisolone alone would be a suitable treatment
7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
8. Female participants of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception, see section 11) and have a negative urine pregnancy test at screening. Male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female participants, effective methods of contraception must be used throughout the trial and for at least 12 months following the last dose of trial treatment
9. Required laboratory values are required at registration and within 14 days prior to randomisation:
9.1. Platelet count ≥50x109/L. Platelet count of 30-50 is acceptable if bone marrow aspirate or trephine shows tumour replacement of >50%. Platelet support is permitted within 14 days prior to randomisation, although platelet transfusions to help participants meet eligibility criteria are not allowed within 72 hours prior to the blood sample to confirm protocol eligibility
9.2. Absolute neutrophil count ≥1.0 x 109/L. Growth factor support is not permitted within 14 days prior to randomisation
9.3. Haemoglobin ≥ 80 g/L. Blood support is permitted
9.4. Alanine transaminase (ALT) and / or aspartate transaminase (AST) ≤3 x upper limit of normal
9.5. Creatinine clearance ≥ 20 ml/min (using Cockcroft Gault formula)
9.6. Bilirubin ≤1.5 x upper limit of normal. Suspected Gilberts syndrome patients must have a total bilirubin ≤3 x upper limit of normal
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 60; UK Sample Size: 60
Participant exclusion criteria
1. The following participants will be excluded:
1.1. Those with non-measurable disease
1.2. Those with a solitary bone or solitary extramedullary plasmacytoma
1.3. Plasma cell leukaemia
2. Participants with a history of malignancy (other than myeloma) within 5 years before the date of randomisation (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that, in the opinion of the investigator, with concurrence with the Chief Investigator, is considered cured with minimal risk of recurrence within 5 years)
3. Participants with a known or underlying uncontrolled concurrent illness that, in the investigator’s opinion, would make the administration of the study drug hazardous or circumstances that could limit compliance with the study, including, but not limited to the following:
3.1. Acute or chronic graft versus host disease
3.2. Uncontrolled hypertension
3.3. Symptomatic congestive heart failure
3.4. Unstable angina pectoris
3.5. Myocardial infarction within past 6 months
3.6. Uncontrolled cardiac arrhythmia
3.7. Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B or C) hepatitis
3.8. Psychiatric or social conditions that may interfere with participant compliance
3.9. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral
3.10. Any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the participant at unacceptable risk for adverse outcome if he/she were to participate in the study
4. Participants who have previously received Selinexor
5. Previous anti-tumour therapies including investigational medicinal products at any dose within 28 days before the start of protocol treatment. (NB: Prednisone up to a dose of 175 mg per week may be given between screening and the beginning of treatment if medically required but should be stopped before trial treatment starts. Bisphosphonates for bone disease are also permitted)
6. Participants with a history of a refractory nausea, diarrhoea, vomiting, malabsorption, gastrointestinal surgery or other procedures or conditions that might, in the opinion of the Investigator, interfere with the absorption or swallowing of the study drug(s)
7. Female participants who are lactating or have a positive pregnancy test at screening
8. Known allergy or intolerance to any of the study medications, their analogues, or excipients in the various formulations of any agent
9. Major surgery within 14 days prior to randomisation
10. Radiotherapy within 7 days prior to randomisation for palliative pain control or therapeutic radiotherapy within 14 days prior to randomisation
11. Chemotherapy or immunotherapy or any other anticancer therapy within 2 weeks prior to Cycle 1 Day 1 or radio-immunotherapy 4 weeks prior to Cycle 1 Day 1 (except steroids in the doses outlined above)
12. Myeloma involving the Central Nervous System
Recruitment start date
01/04/2018
Recruitment end date
31/10/2020
Locations
Countries of recruitment
United Kingdom
Trial participating centre
The Royal Marsden
Downs Road
Sutton
SM2 5PT
United Kingdom
Trial participating centre
St Bartholomew’s
Royal London Hospital
London
E1 1BB
United Kingdom
Trial participating centre
Imperial College London
Hammersmith Hospital
Du Cane Road
London
W12 0NN
United Kingdom
Trial participating centre
Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Funders
Funder type
Charity
Funder name
Myeloma UK; Grant Codes: HM17/95228
Alternative name(s)
Myeloma United Kingdom
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit organizations
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The protocol will be published. Planned publication of the results in a high-impact peer-reviewed journal, 12 months after the trial ends
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date
Intention to publish date
01/04/2022
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list