Phase II Randomised Trial of Cyclophosphamide & Dexamethasone in Combination With Ixazomib in Relapsed or Refractory Multiple Myeloma.

Inclusion Criteria:

* 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
* 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

Exclusion Criteria:

* 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.
* 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