Condition category
Cancer
Date applied
05/03/2018
Date assigned
21/03/2018
Last edited
21/03/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Relapsed and refractory multiple myeloma (RRMM) is a type of bone marrow cancer that has returned after treatment or a period of remission and is not responsive to treatment. The aim of this study is to compare two different combinations of drugs used to treat multiple myeloma that has relapsed after two or more lines of treatment. 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 RRMM. 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 (SCP), with cyclophosphamide and prednisone alone followed by SCP at disease progression.

Who can participate?
Patients aged 18 or over with RRMM

What does the study involve?
Participants are randomly allocated to be treated with either selinexor + cyclophosphamide + prednisolone (SCP) or cyclophosphamide + prednisolone (CP). Participants who experience disease progression on the CP arm may receive SCP once progression has been confirmed and the participant has been deemed eligible to receive SCP. All patients are followed up for at least 6 months or until they have progressed on the first phase of treatment (whichever is sooner).

What are the possible benefits and risks of participating?
Selinexor has shown promising results in solid tumour and myeloma studies conducted so far. The results of this study will inform further later phase studies with this drug in the UK. Due to the cross-over design all participants have a realistic chance of receiving selinexor.

Where is the study run from?
1. The Royal Marsden Hospital (UK)
2. Royal London Hospital (UK)
3. Hammersmith Hospital (UK)
4. Leicester Royal Infirmary (UK)

When is the study starting and how long is it expected to run for?
December 2016 to April 2021

Who is funding the study?
Myeloma UK

Who is the main contact?
Rowena Henderson

Trial website

Contact information

Type

Scientific

Primary contact

Miss Rowena Henderson

ORCID ID

Contact details

CTRU
University of Leeds
Leeds
LS2 9JT
United Kingdom

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

Specialty: Cancer, Primary sub-specialty: Haematological Oncology; UKCRC code/ Disease: Cancer/ Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissu

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

Other

Phase

Phase II

Drug names

Primary outcome measures

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

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

Trial participating centre

St Bartholomew’s
Royal London Hospital
London
E1 1BB

Trial participating centre

Imperial College London
Hammersmith Hospital Du Cane Road
London
W12 0NN

Trial participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW

Sponsor information

Organisation

University of Leeds

Sponsor details

Research and Innovation Support
University of Leeds
Leeds
LS2 9JT
United Kingdom

Sponsor type

University/education

Website

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

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes