Plain English Summary
Trial website
Additional identifiers
EudraCT number
2014-004511-36
ClinicalTrials.gov number
Protocol/serial number
19412
Study information
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.
Acronym
MUK Eight
Study hypothesis
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
North West-Liverpool East, 12/06/2015, ref: 15/NW/0416
Study design
Randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
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
Phase
Phase II
Drug names
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 trial start date
01/09/2015
Overall trial end date
01/09/2017
Reason abandoned (if study stopped)
Eligibility
Participant 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: 1.Paraprotein >5g/L or 0.5 g/l for IgD subtype; 5. Serum free light chains >100mg/L with abnormal radio for light chain only myeloma; 3.Bence Jones protein >200mg/L
6. Participants with relapsed or relapsed refractory myeloma and now require further treatment following exposure to thalidomide, lenalidomide and bortezomib regardless of response to these
7. ECOG Performance Status = 2
8. Required laboratory values within 14 days prior to Randomisation:
8.1. 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
8.2. Absolute neutrophil count =1.0 x 109/L. Growth factor support is not permitted within 14 days prior to randomisation
8.3. Haemoglobin > 9 g/dL. Blood support is permitted
8.4. ALT and / or AST =3 x upper limit of normal
8.5. Creatinine clearance = 30 ml/min (using Cockcroft Gault formula)
8.6. Bilirubin =1.5 x upper limit of normal
9.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
10. Post allograft patients may be included if >12 months from transplant
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 250; UK Sample Size: 250
Participant 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
Recruitment start date
01/10/2015
Recruitment end date
01/09/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
St James Hospital (lead centre)
Leeds
LS9 7TF
United Kingdom
Trial participating centre
St Bartholomew’s Hospital
London
EC1M 6BQ
United Kingdom
Trial participating centre
Bristol Haematology and Oncology Centre
Horfield Rd
Avon
Bristol
BS2 8ED
United Kingdom
Trial participating centre
The Christie NHS Foundation Trust
550 Wilmslow Rd
Manchester
M20 4BX
United Kingdom
Trial participating centre
Guys & St Thomas’ NHS Foundation Trust
London
SE1 9RT
United Kingdom
Trial participating centre
Birmingham Heartlands Hospital
Bordesley Green East
Bordesley Green
Birmingham
B9 5SS
United Kingdom
Trial participating centre
Imperial College Healthcare
London
SW7 9RT
United Kingdom
Trial participating centre
Nottingham University Hospital
Derby Rd
Nottingham
NG7 2UH
United Kingdom
Trial participating centre
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
Trial participating centre
Queen Elizabeth Hospital
Queen Elizabeth Medical Centre
Birmingham
B15 2TH
United Kingdom
Trial participating centre
Royal Liverpool University Hospital
Prescot Street
Liverpool, Merseyside
L7 8XP
United Kingdom
Trial participating centre
The Royal Marsden NHS Foundation Trust
Downs Rd
Sutton
Surrey
SM2 5PT
United Kingdom
Trial participating centre
Royal Hallamshire Hospital
Glossop Rd
Sheffield, South Yorkshire
S10 2SJ
United Kingdom
Trial participating centre
Southampton General Hospital
Tremona Rd
Southampton, Hampshire
SO16 6YD
United Kingdom
Trial participating centre
Singleton Hospital
Sketty Ln
Sketty
Swansea
SA2 8QA
United Kingdom
Trial participating centre
University College London
250 Euston Road
London
NW1 2PG
United Kingdom
Trial participating centre
New Cross Hospital
Wednesfield Rd
Wolverhampton, West Midlands
WV10 0QP
United Kingdom
Funders
Funder type
Charity
Funder name
Myeloma UK
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not expected to be available
Basic results (scientific)
Publication list