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.
| ISRCTN | ISRCTN58227268 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN58227268 |
| EudraCT/CTIS number | 2014-004511-36 |
| Secondary identifying numbers | CPMS 19412 |
- Submission date
- 26/08/2015
- Registration date
- 26/08/2015
- Last edited
- 20/06/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Dr S N Roberts
Scientific
Scientific
Leeds Institute of Clinical Trials Research
Level 10 Worsley Building
University of Leeds
Leeds
LS2 9JT
United Kingdom
| ctru_mukseven@leeds.ac.uk |
Study information
| Study design | Randomized; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific 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. |
| Study acronym | MUK Eight |
| Study objectives | The aim of this study is to run a phase II trial of cyclophosphamide and dexamethasone in combination with Ixazomib (MLN9708), in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenalidomide and bortezomib. |
| Ethics approval(s) | North West-Liverpool East, 12/06/2015, ref: 15/NW/0416 |
| Health condition(s) or problem(s) studied | Topic: Cancer; Subtopic: Haematological Oncology; Disease: Myeloma |
| Intervention | Participants will be randomised to receive either ICD (ixazomib, cyclophosphamide and dexamethasone) or CD (cyclophosphamide and dexamethasone). All cycles of treatment consist of 28 days and treatment will continue until disease progression death, unacceptable toxicity or withdrawal of consent, whichever is sooner. |
| Intervention type | Other |
| Primary outcome measure | To evaluate whether ICD has improved clinical activity compared to CD in patients with RRMM |
| Secondary outcome measures | 1. To further evaluate the clinical activity of ICD with regard to additional secondary endpoints 2. To determine the safety and toxicity profile of ICD 3. To determine the cost-effectiveness of ICD compared to CD 4. To determine quality of life with ICD 5. To assess the impact of baseline Charlson index score on 6. Outcomes and deliverability of treatment |
| Overall study start date | 01/09/2015 |
| Completion date | 30/06/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 250; UK Sample Size: 250 |
| Total final enrolment | 112 |
| Key inclusion criteria | 1. Able to give informed consent and willing to follow study protocol assessments 2. Aged 18 years or over 3. Participants with confirmed MM based on IMWG criteria, 2009 4. Measurable disease with at least one of the following: 4.1. Paraprotein >5g/L or 0.5 g/l for IgD subtype; 4.2. Serum-free light chains >100mg/L with abnormal radio for light chain only myeloma; 4.3. Bence Jones protein >200mg/L 5. Participants with relapsed or relapsed refractory myeloma and now require further treatment following exposure to thalidomide, lenalidomide and bortezomib regardless of response to these 6. ECOG Performance Status = 2 7. Required laboratory values within 14 days prior to Randomisation: 7.1. Platelet count =50x109/L. Platelet count of 3050 is acceptable if bone marrow aspirate shows tumour replacement of >50%. Platelet support is permitted within 14 days prior to randomisation although platelet transfusions to help patients meet eligibility criteria are not allowed within 72 hours prior to the blood sample to confirm protocol eligibility 7.2. Absolute neutrophil count =1.0 x 109/L. Growth factor support is not permitted within 14 days prior to randomisation 7.3. Haemoglobin > 9 g/dL. Blood support is permitted 7.4. ALT and / or AST =3 x upper limit of normal 7.5. Creatinine clearance = 30 ml/min (using Cockcroft Gault formula) 7.6. Bilirubin =1.5 x upper limit of normal 8. Female participants should avoid becoming pregnant and male participants should avoid impregnating a female partner. Both nonsterilised and sterilised females and males of reproductive age should use effective methods of contraception during the entire trial treatment (including treatment breaks) and up to 90 days after the last dose of trial treatment 9. Post-allograft patients may be included if >12 months from transplant |
| Key exclusion criteria | 1.Those with nonmeasurable disease, a solitary bone or solitary extramedullary plasmacytoma, Plasma cell leukaemia 2. Prior malignancy other than those treated with surgery. 3. Participants with a known or underlying uncontrolled concurrent illness that, in the investigators 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: acute or chronic graft versus host disease, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within past 6 months, uncontrolled cardiac arrhythmia, renal failure, psychiatric or social conditions that may interfere with participant compliance, or 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. Patients who have previously received Ixazomib or MLN9708 in a trial. Previous experimental agents or approved anti-tumour treatment within 30 days before the date of randomisation. 5. A maximum of 160mg of dexamethasone (in 40mg blocks) 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 and radiotherapy for palliative intent are also permitted. 6. Participants with a history of a refractory nausea, diarrhoea, vomiting, malabsorption, gastrointestinal surgery or other procedures that might, in the opinion of the Investigator, interfere with the absorption or swallowing of the study drug(s) 7. Peripheral neuropathy of = grade 2 (or grade 1 with pain) severity (as per NCICTCAEv4.0) 8. Gastrointestinal disorders that may interfere with absorption of the study drug 9. Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B or C) hepatitis 10. Female patients who are lactating or have a positive pregnancy test during the screening period 11. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent 12. Systemic treatment, within 14 days before the first dose of Ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort 13. Major surgery within 14 days prior to the date of randomisation 14. Radiotherapy within 7 days for palliative pain control or therapeutic radiotherapy within 14 days prior to randomisation 15. Myeloma involving the Central Nervous System |
| Date of first enrolment | 01/10/2015 |
| Date of final enrolment | 01/09/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
- Wales
Study participating centres
St James Hospital (lead centre)
Leeds
LS9 7TF
United Kingdom
LS9 7TF
United Kingdom
St Bartholomew’s Hospital
London
EC1M 6BQ
United Kingdom
EC1M 6BQ
United Kingdom
Bristol Haematology and Oncology Centre
Horfield Rd
Avon
Bristol
BS2 8ED
United Kingdom
Avon
Bristol
BS2 8ED
United Kingdom
The Christie NHS Foundation Trust
550 Wilmslow Rd
Manchester
M20 4BX
United Kingdom
Manchester
M20 4BX
United Kingdom
Guys & St Thomas’ NHS Foundation Trust
London
SE1 9RT
United Kingdom
SE1 9RT
United Kingdom
Birmingham Heartlands Hospital
Bordesley Green East
Bordesley Green
Birmingham
B9 5SS
United Kingdom
Bordesley Green
Birmingham
B9 5SS
United Kingdom
Imperial College Healthcare
London
SW7 9RT
United Kingdom
SW7 9RT
United Kingdom
Nottingham University Hospital
Derby Rd
Nottingham
NG7 2UH
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
OX3 7LE
United Kingdom
Queen Elizabeth Hospital
Queen Elizabeth Medical Centre
Birmingham
B15 2TH
United Kingdom
Birmingham
B15 2TH
United Kingdom
Royal Liverpool University Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom
Liverpool
L7 8XP
United Kingdom
The Royal Marsden NHS Foundation Trust
Downs Rd
Sutton
SM2 5PT
United Kingdom
Sutton
SM2 5PT
United Kingdom
Royal Hallamshire Hospital
Glossop Rd
Sheffield
S10 2SJ
United Kingdom
Sheffield
S10 2SJ
United Kingdom
Southampton General Hospital
Tremona Rd
Southampton
SO16 6YD
United Kingdom
Southampton
SO16 6YD
United Kingdom
Singleton Hospital
Sketty Ln
Sketty
Swansea
SA2 8QA
United Kingdom
Sketty
Swansea
SA2 8QA
United Kingdom
University College London
250 Euston Road
London
NW1 2PG
United Kingdom
London
NW1 2PG
United Kingdom
New Cross Hospital
Wednesfield Rd
Wolverhampton
WV10 0QP
United Kingdom
Wolverhampton
WV10 0QP
United Kingdom
Sponsor information
University of Leeds
University/education
University/education
Clinical Trials Research Unit
Fairbairn House
71-75 Clarendon Road
Leeds
LS2 9PH
England
United Kingdom
"ROR" |
https://ror.org/024mrxd33 |
|---|
Funders
Funder type
Charity
Myeloma UK
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | De-identified individual participant data datasets generated and/or analysed during the current study will be available upon request from the Clinical Trials Research Unit, University of Leeds (contact CTRU-DataAccess@leeds.ac.uk in the first instance). Data will be made available at the end of the trial, i.e. usually when all primary and secondary endpoints have been met and all key analyses are complete. Data will remain available from then on for as long as CTRU retains the data. CTRU makes data available by a 'controlled access' approach. Data will only be released for legitimate secondary research purposes, where the Chief Investigator, Sponsor and CTRU agree that the proposed use has scientific value and will be carried out to a high standard (in terms of scientific rigour and information governance and security), and that there are resources available to satisfy the request. Data will only be released in line with participants' consent, all applicable laws relating to data protection and confidentiality, and any contractual obligations to which the CTRU is subject. No individual participant data will be released before an appropriate agreement is in place setting out the conditions of release. The agreement will govern data retention, usually stipulating that data recipients must delete their copy of the released data at the end of the planned project. The CTRU encourages a collaborative approach to data sharing, and believe it is best practice for researchers who generated datasets to be involved in subsequent uses of those datasets. Recipients of trial data for secondary research will also receive data dictionaries, copies of key trial documents and any other information required to understand and reuse the released datasets. The conditions of release for aggregate data may differ from those applying to individual participant data. Requests for aggregate data should also be sent to the above email address to discuss and agree suitable requirements for release. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 02/10/2020 | 07/10/2020 | Yes | No |
| Results article | 01/04/2022 | 04/04/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Abstract results | P11 | 17/04/2022 | 12/09/2023 | No | No |
| Poster results | 17/04/2022 | 12/09/2023 | No | No | |
| Plain English results | 12/02/2025 | No | Yes |
Editorial Notes
20/06/2025: The overall end date was changed from 30/06/2025 to 30/06/2026.
12/02/2025: Cancer Research UK plain English results added.
18/12/2024: The overall end date was changed from 01/12/2024 to 30/06/2025.
22/04/2024: The overall end date was changed from 01/09/2017 to 01/12/2024.
12/09/2023: Publication references added.
22/07/2022: Internal review.
18/07/2022: IPD sharing statement and total final enrolment added. Contact details updated.
04/04/2022: Publication reference added.
07/10/2020: Publication reference added.
14/06/2016: Cancer Help UK lay summary link added.
