Multiple MyelomaPhase 2MUKEightNCT02461888
Phase II Randomised Trial of Cyclophosphamide & Dexamethasone in Combination With Ixazomib in Relapsed or Refractory Multiple Myeloma.
A Phase 2 study testing Ixazomib, Cyclophosphamide and Dexamethasone in people with Multiple Myeloma, run by University of Leeds at 18 sites in United Kingdom.
Trial summary
This study evaluates a new treatment combination of ixazomib with cyclophosphamide and dexamethasone in relapsed or refractory multiple myeloma. Participants will either receive ixazomib with cyclophosphamide and dexamethasone or cyclophosphamide and dexamethasone alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Ixazomib, Cyclophosphamide and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 18 sitesUnited Kingdom
- Study dates
- Dec 2015to 19 Jan 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to give informed consent and willing to follow study protocol assessments
- Aged 18 years or over
- Participants with confirmed multiple myeloma based on International Myeloma Working Group (IMWG) criteria, 2009
- Measurable disease
- Participants with relapsed or relapsed refractory myeloma and now require further treatment following exposure to thalidomide, lenalidomide and bortezomib regardless of response to these
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
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- Required laboratory values within 14 days prior to Randomisation:
- Platelet count ≥50x109/L. Platelet support is permitted within 14 days prior to Randomisation
- Absolute neutrophil count ≥1.0 x 109/L
- Haemoglobin > 9 g/dL. Blood support is permitted
- Alanine aminotransferase (ALT) and / or Aspartate aminotransferase (AST) ≤3 x upper limit of normal
- Creatinine clearance ≥ 30 ml/min (using Cockcroft Gault formula)
- Bilirubin ≤1.5 x upper limit of normal
- Both non-sterilised 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
- Post allograft patients may be included
Who cannot join
- Those with non-measurable disease
- Those with a solitary bone or solitary extramedullary plasmacytoma
- Plasma cell leukaemia
- Prior malignancy other than those treated with curative surgery.
- 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
- Patients who have previously received MLN9708/Ixazomib in a trial. Previous experimental agents or approved anti-tumour treatment within 30 days before the date of randomisation.
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- 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
- 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)
- Peripheral neuropathy of ≥ grade 2 severity
- Gastrointestinal disorders that may interfere with absorption of the study drug
- Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B or C) hepatitis
- Female patients who are lactating or have a positive serum pregnancy test during the screening period
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
- Systemic treatment, within 14 days before the first dose of MLN9708, 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
- Major surgery within 14 days prior to the date of randomisation
- Radiotherapy within 14 days prior to randomisation
- Disease involving the Central Nervous System
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United Kingdom18 sites
Queen Elizabeth Medical Centre
Birmingham, B15 2TH
Heart of England NHS Foundation Trust
Birmingham, B9 5ST
Royal Bournemouth General Hospital
Bournemouth, BH7 7DW
University Hospital Bristol NHS Foundation Trust
Bristol, BS1 3NU
North Tees and Hartlepool NHS Foundation Trust
Hartlepool, TS24 9AH
Leeds Teaching Hospitals NHS Trust
Leeds, LS9 7TF
Royal Liverpool and Broadgreen University Hospital NHS Trust
Liverpool, L7 8XP
Barts and the London NHS Trust
London, E1 1BB
University College London Hospitals NHS Foundation Trust
London, NW1 2PG
Guy's and St Thomas's NHS Foundation Trust
London, SE1 9RT
Royal Marsden Hospital
London, SW3 6JJ
Imperial College Healthcare NHS Trust
London, W2 1NY
The Christie NHS Foundation Trust
Manchester, M20 4BX
Nottingham University Hospital NHS Trust
Nottingham, NG7 2UH
Churchill Hospital
Oxford, OX3 7LE
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, S5 7AU
Southampton University Hospital NHS Trust
Southampton, SO16 6YD
The Royal Wolverhampton Hospital NHS Trust
Wolverhampton, WV10 0QP
About this study
Official 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, Lenalidomide and Bortezomib.
This study evaluates a new treatment combination of ixazomib with cyclophosphamide and dexamethasone in relapsed or refractory multiple myeloma. Participants will either receive ixazomib with cyclophosphamide and dexamethasone or cyclophosphamide and dexamethasone alone.
Read the detailed description
Cyclophosphamide and dexamethasone are very commonly used in the treatment of multiple myeloma and are often given with a third drug (e.g. thalidomide, lenalidomide or bortezomib). The combination of conventional and new drugs has provided benefits in both overall survival and progression free survival, however there are few treatments available for patients who have not responded well (refractory) to their previous treatment or who need further treatment because their myeloma has come back (relapsed). Thus there is a need for new agents for these patients.
The development of ixazomib provides the opportunity to increase anti-tumour activity against a wider range of tumour types. Early clinical trials data suggests it has anti-tumour activity in heavily pre-treated multiple myeloma patients with durable responses/disease control and is generally well tolerated.
Cyclophosphamide and dexamethasone are both predominantly used in treatment of multiple myeloma and for patients with relapsed or refractory multiple myelomas (RRMM), who have relapsed after bortezomib and lenalidomide. Therefore the evaluation of ixazomib in combination with cyclophosphamide and dexamethasone is the most valuable and practical option for patients.
The primary end point of this study is progression-free survival (PFS). Secondary end points include toxicity and safety.
- Conditions
- Multiple Myeloma
- Being tested
- Ixazomib, Cyclophosphamide, Dexamethasone
- Keywords
- Relapsed, Refractory, Cyclophosphamide, Dexamethasone
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IxazomibDrug
Chemotherapy
CyclophosphamideDrug
Chemotherapy
DexamethasoneDrug
Chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Ixazomib, CD | Experimental | Ixazomib, cyclophosphamide and dexamethasone (ICD) will be administered as part of a 28 days cycle until disease progression, intolerance, toxicity or withdrawal.
Dosing schedule:
* Ixazomib 4mg orally on days 1, 8 and 15
* Cyclophosphamide 500mg orally on days 1, 8 and 15
* Dexamethasone 40mg orally on days 1-4 and 12-15 Receives: Drug: Ixazomib; Drug: Cyclophosphamide; Drug: Dexamethasone |
| CD | Active comparator | Cyclophosphamide and dexamethasone (CD) will be administered as part of a 28 days cycle until disease progression, intolerance, toxicity or withdrawal.
Dosing schedule:
* Cyclophosphamide 500mg orally on days 1, 8 and 15
* Dexamethasone 40mg orally on days 1-4 and 12-15 Receives: Drug: Cyclophosphamide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Measured: From randomisation to first documented evidence of disease progression or death, up to 36 months.
Secondary outcomes (10)
Response to treatment
Measured: From initial trial treatment until at least partial response is achieved, up to 36 months..
Maximum response
Measured: From initial trial treatment each of the response categories are achieved stringent complete response, complete response, very good partial response, partial response, minimal response or stable disease, up to 36 months.
Time to progression
Measured: From randomisation to first documented evidence of disease progression, up to 36 months..
Time to maximum response
Measured: From randomisation until the participant achieves any of the categories stringent complete response, complete response, very good partial response, partial response, minimal response or stable disease, up to 36 months.
Response duration
Measured: From the first observation of at least partial response until disease progression, up to 36 months.
Overall survival
Measured: From randomisation to death, up to 36 months.
Evaluate the safety and toxicity as measured by adverse reactions and serious adverse event reporting.
Measured: From consent until 28 days after the last dose of trial treatment, up to 36 months.
Treatment compliance measured by treatment delays and missed treatment doses.
Measured: From initial treatment received as per protocol until withdrawal from treatment, up to 36 months.
Quality of life measured by the completion of EQ-5D and EORTC QLQ-C30 questionnaires
Measured: Completed every 3 months from consent until disease progression, up to 36 months.
Cost effectiveness of treatment assessed by health economic evaluations.
Measured: From consent up to 36 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2015 (estimated)
- Study startDec 2015
- Primary completionApr 2022
- Study completion19 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Collaborators
- Myeloma UK, Millennium Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Gordon Cook, University of Leeds
- Investigators
- Gordon Cook, Principal investigator, Leeds Teaching Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02461888
- Sponsor's protocol ID
- HM13/10993
- Acronym
- MUKEight
- Status last verified
- Dec 2025
- First submitted
- 1 Jun 2015
- Last updated
- 17 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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, Lenalidomide and Bortezomib.
- ClinicalTrials.gov ID
- NCT02461888
- Acronym / sponsor ID
- MUKEight / HM13/10993
- Conditions
- Multiple Myeloma
- Keywords
- Relapsed, Refractory, Cyclophosphamide, Dexamethasone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Collaborators
- Myeloma UK, Millennium Pharmaceuticals, Inc.
- Study start
- Dec 2015 (actual)
- Primary completion
- Apr 2022 (actual)
- Study completion
- 19 Jan 2025 (actual)
- First posted
- 3 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates a new treatment combination of ixazomib with cyclophosphamide and dexamethasone in relapsed or refractory multiple myeloma. Participants will either receive ixazomib with cyclophosphamide and dexamethasone or cyclophosphamide and dexamethasone alone.
Detailed description
Cyclophosphamide and dexamethasone are very commonly used in the treatment of multiple myeloma and are often given with a third drug (e.g. thalidomide, lenalidomide or bortezomib). The combination of conventional and new drugs has provided benefits in both overall survival and progression free survival, however there are few treatments available for patients who have not responded well (refractory) to their previous treatment or who need further treatment because their myeloma has come back (relapsed). Thus there is a need for new agents for these patients.
The development of ixazomib provides the opportunity to increase anti-tumour activity against a wider range of tumour types. Early clinical trials data suggests it has anti-tumour activity in heavily pre-treated multiple myeloma patients with durable responses/disease control and is generally well tolerated.
Cyclophosphamide and dexamethasone are both predominantly used in treatment of multiple myeloma and for patients with relapsed or refractory multiple myelomas (RRMM), who have relapsed after bortezomib and lenalidomide. Therefore the evaluation of ixazomib in combination with cyclophosphamide and dexamethasone is the most valuable and practical option for patients.
The primary end point of this study is progression-free survival (PFS). Secondary end points include toxicity and safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ixazomib, CD | Experimental | Drug: Ixazomib, Drug: Cyclophosphamide, Drug: DexamethasoneIxazomib, cyclophosphamide and dexamethasone (ICD) will be administered as part of a 28 days cycle until disease progression, intolerance, toxicity or withdrawal. Dosing schedule: * Ixazomib 4mg orally on days 1, 8 and 15 * Cyclophosphamide 500mg orally on days 1, 8 and 15 * Dexamethasone 40mg orally on days 1-4 and 12-15 |
| CD | Active comparator | Drug: Cyclophosphamide, Drug: DexamethasoneCyclophosphamide and dexamethasone (CD) will be administered as part of a 28 days cycle until disease progression, intolerance, toxicity or withdrawal. Dosing schedule: * Cyclophosphamide 500mg orally on days 1, 8 and 15 * Dexamethasone 40mg orally on days 1-4 and 12-15 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Able to give informed consent and willing to follow study protocol assessments
- Aged 18 years or over
- Participants with confirmed multiple myeloma based on International Myeloma Working Group (IMWG) criteria, 2009
- Measurable disease
- Participants with relapsed or relapsed refractory myeloma and now require further treatment following exposure to thalidomide, lenalidomide and bortezomib regardless of response to these
Key exclusion criteria (17 listed)
- Those with non-measurable disease
- Those with a solitary bone or solitary extramedullary plasmacytoma
- Plasma cell leukaemia
- Prior malignancy other than those treated with curative surgery.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IxazomibChemotherapy | Drug | Ixazomib, CD |
| CyclophosphamideChemotherapy | Drug | CD, Ixazomib, CD |
| DexamethasoneChemotherapy | Drug | CD, Ixazomib, CD |
Primary outcome
Progression free survival
Time frame: From randomisation to first documented evidence of disease progression or death, up to 36 months.
10 secondary outcomes
Response to treatment
Time frame: From initial trial treatment until at least partial response is achieved, up to 36 months..
Maximum response
Time frame: From initial trial treatment each of the response categories are achieved stringent complete response, complete response, very good partial response, partial response, minimal response or stable disease, up to 36 months.
Time to progression
Time frame: From randomisation to first documented evidence of disease progression, up to 36 months..
Time to maximum response
Time frame: From randomisation until the participant achieves any of the categories stringent complete response, complete response, very good partial response, partial response, minimal response or stable disease, up to 36 months.
Response duration
Time frame: From the first observation of at least partial response until disease progression, up to 36 months.
Overall survival
Time frame: From randomisation to death, up to 36 months.
Evaluate the safety and toxicity as measured by adverse reactions and serious adverse event reporting.
Time frame: From consent until 28 days after the last dose of trial treatment, up to 36 months.
Treatment compliance measured by treatment delays and missed treatment doses.
Time frame: From initial treatment received as per protocol until withdrawal from treatment, up to 36 months.
Quality of life measured by the completion of EQ-5D and EORTC QLQ-C30 questionnaires
Time frame: Completed every 3 months from consent until disease progression, up to 36 months.
Cost effectiveness of treatment assessed by health economic evaluations.
Time frame: From consent up to 36 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gordon Cook principal investigator
Leeds Teaching Hospitals NHS Trust
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ixazomib, Cyclophosphamide and Dexamethasone in people with Multiple Myeloma, run by University of Leeds at 18 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: From randomisation to first documented evidence of disease progression or death, up to 36 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2025.