The Role of Ixazomib in Autologous Stem Cell Transplant in Relapsed Myeloma - Myeloma XII (ACCoRd)

Inclusion Criteria:

1. Diagnosed with relapsed MM (with measurable disease, according to IMWG criteria (Appendix 2)) previously treated with ASCT).

2. First Progressive Disease (PD) at least 12 months following first ASCT, requiringtherapy.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 (Appendix 3).

4. Aged at least 18 years.

5. Participants must have the following blood results within 14 days before registration:

6. Absolute neutrophil count (ANC) ≥1x109/L

7. Platelet count ≥75x109/L. If the participant has ≥50% bone marrow infiltration aplatelet count of ≥50x109/L is allowed. Platelet transfusions are not allowed within 3 days before registration in order tomeet these values.

8. Adequate renal function within 14 days before registration: a. Creatinine clearance ≥30ml/min (calculated according to the Cockcroft-Gaultequation or other locally approved formula)

9. Adequate hepatobiliary function within 14 days before registration:

10. Total bilirubin <2 x upper limit of normal (ULN)

11. ALT <2 x ULN

12. Adequate pulmonary function within 14 days before registration: a. Adequate respiratory functional reserve (delineated by KCO/DLCO (carbon monoxidediffusion in the lung) of ≥50%). No evidence of a history of pulmonary disease. If asignificant history, then a review by a respiratory medicine physician is required.

13. Adequate cardiac function within 12 weeks before registration a. Left ventricular ejection fraction (LVEF) ≥40%. Note: repeat confirmation ofcardiac function is needed if treatment is given between this assessment andregistration.

14. Female participants who:

15. Are not of childbearing potential (Appendix 8), OR

16. If they are of childbearing potential (Appendix 8), agree to practice 2 effectivemethods of contraception (Appendix 8), at the same time, from the time of signingthe informed consent form until 90 days after the last dose of study drug, OR

17. Agree to practice true abstinence when this is in line with the preferred andusual lifestyle of the subject. (Periodic abstinence [e.g. calendar, ovulation,symptothermal, post-ovulation methods] and withdrawal are not acceptable methodsof contraception.) Male participants, even if surgically sterilised (i.e. status post-vasectomy), mustagree to one of the following:

18. Agree to practice effective barrier contraception during the entire studytreatment period and through 90 days after the last dose of study drug, OR

19. Agree to practice true abstinence when this is in line with the preferred andusual lifestyle of the subject. (Periodic abstinence (e.g. calendar, ovulation,symptothermal, post-ovulation methods] and withdrawal are not acceptable methodsof contraception.) Contraception for female and male participants must be inaccordance with (and consent to) the Celgene-approved Thalidomide PregnancyPrevention Programme.

20. If female and of childbearing potential (see Appendix 8), must have a negativepregnancy test performed by a healthcare professional in accordance with the CelgeneThalidomide Pregnancy Prevention Programme.

21. Patients agree not to receive other clinical trials treatment, includinginvestigational medicinal products (IMPs) not included in this trial, within 30 daysof trial registration and throughout the duration of the trial, until diseaseprogression.

22. Able to provide written informed consent.

Exclusion Criteria:

1. Received prior second line therapy for their relapsed disease other than localradiotherapy, therapeutic plasma exchange, or dexamethasone (up to a maximum of 200mgis allowed but not within 30 days prior to registration). Radiotherapy sufficient toalleviate or control pain of local invasion is permitted, but must not be within 14days before registration. Patients who have received hemi-body radiation or similarsince relapse will not be eligible.

2. ≥Grade 2 peripheral neuropathy within 14 days before registration.

3. Known HIV seropositivity.

4. Known resistance, intolerance or sensitivity to any component of the plannedtherapies.

5. Any medical or psychiatric condition which, in the opinion of the investigator,contraindicates the participant's participation in this study.

6. Previous or concurrent malignancies at other sites (excluding completely resectednon-melanoma skin cancer or carcinoma in situ of any type, such as cervical cancer).

7. Pregnant, lactating or breast feeding female participants.

8. Failure to have fully recovered (i.e.Grade 1 or less toxicity) from the reversibleeffects of prior chemotherapy.

9. Major surgery within 14 days before registration.

10. Central nervous system involvement with myeloma.

11. Ongoing or active infection requiring systemic antibiotic therapy or other seriousinfection within 14 days before registration.

12. Evidence of current uncontrolled cardiovascular conditions, including uncontrolledhypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,unstable angina, or myocardial infarction within the past 6 months.

13. Systemic treatment, within 14 days before the first dose of ixazomib with strong CYP3Ainducers (e.g. rifampin, rifapentine, rifabutin, carbamazepine, phenytoin,phenobarbital), or use of Ginkgo biloba or St. John's wort.

14. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oralabsorption or tolerance of ixazomib, including difficulty swallowing.

15. Patients that have previously been treated with ixazomib or participated in a studywith ixazomib whether treated with ixazomib or not.

16. Participant has current or prior hepatitis B or C infection.