Condition category
Cancer
Date applied
26/08/2015
Date assigned
26/08/2015
Last edited
14/06/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Ms Kiren Ajab

ORCID ID

Contact details

CTRU
Clinical Trials Research House
Fairbairn House
71-75 Clarendon Road
Leeds
LS2 9PH
United Kingdom

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 measures

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

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

Sponsor information

Organisation

University of Leeds

Sponsor details

Clinical Trials Research Unit
Fairbairn House
71-75 Clarendon Road
Leeds
LS2 9PH
United Kingdom

Sponsor type

University/education

Website

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

14/06/2016: Cancer Help UK lay summary link added.