A Phase 3 Study Comparing Oral Ixazomib Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma

Inclusion Criteria: 1. Male or female participants 18 years of age or older. 2. Multiple myeloma diagnosed according to standard criteria either currently or at the time of initial diagnosis. NOTE: The initial diagnosis must have been symptomatic multiple myeloma, although the relapsed disease did not need to be symptomatic. 3. Must have had measurable disease, defined by at least 1 of the following 3 measurements: * Serum M-protein ≥ 1 g/dL (≥ 10 g/L). * Urine M-protein ≥ 200 mg/24 hours. * Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL (≥ 100 mg/L), provided that the serum FLC ratio was abnormal. 4. Participants with relapsed and/or refractory multiple myeloma (RRMM) who had received 1 to 3 prior therapies. NOTE: population included the following 3 categories of participants: * Participants who relapsed from their previous treatment(s) but were not refractory to any previous treatment. * Participants who were refractory to all lines of previous treatment(s) (ie, participants who had never responded to any therapies received). * Participants who relapsed from at least 1 previous treatment AND additionally were refractory to at least 1 previous treatment. For the purposes of this study, refractory disease was defined as disease progression on treatment or progression within 60 days after the last dose of a given therapy. A line of therapy was defined as 1 or more cycles of a planned treatment program. This may have consisted of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation, followed by maintenance was considered 1 line of therapy. Autologous and allogenic transplants were permitted. 5. Must have met the following clinical laboratory criteria: * Absolute neutrophil count (ANC) ≥ 1000/mm\^3 and platelet count ≥ 75,000/mm\^3. Platelet transfusions to help participants meet eligibility criteria were not allowed within 3 days prior to randomization. * Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN). * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN. * Calculated creatinine clearance ≥ 30 mL/min NOTE: Participants with a low creatinine clearance ≤ 60 mL/min (or ≤ 50 mL/min, according to lenalidomide prescribing information/local practice) were to receive a reduced lenalidomide dose of 10 mg once daily (QD) on Days 1 through 21 of a 28-day cycle. The lenalidomide dose may have been escalated to 15 mg QD after 2 cycles if the participant was not responding to treatment and was tolerating the treatment. If renal function normalized (ie, creatinine clearance \>60 mL/min or \>50 mL/min, according to lenalidomide prescribing information/local practice) and the participant continued to tolerate this treatment, lenalidomide may then have been escalated to 25 mg QD. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 7. Participants who received prior allogenic transplant must have had no active graft-versus-host disease. 8. Female participants who: * Were postmenopausal for at least 24 months before the screening visit, OR * Were surgically sterile, OR * If they were of childbearing potential must have: had a negative pregnancy test with a sensitivity of at least 25 mIU/mL within 10 to 14 days and again within 24 hours prior to starting Cycle 1 of lenalidomide; either agreed to practice true abstinence, when this was in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal were not acceptable methods of contraception.) OR begun 2 reliable methods of birth control (1 highly effective method and 1 additional effective method) at the same time, at least 28 days before starting study treatment through 90 days after the last dose of study treatment; and agreed to ongoing pregnancy testing AND must have also adhered to the guidelines of the RevAssist program (US participants), RevAid program (Canadian participants), iAccess program (Australian participants), RevMate program (Japanese participants) or The Lenalidomide Pregnancy Risk Minimisation Plan as outlined in the Study Manual (all other participants who were not using commercial supplies). Male patients, even if surgically sterilized (ie, status postvasectomy), who: * Agreed to practice true abstinence, when this was in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal were not acceptable methods of contraception.) OR * Agreed to practice effective barrier contraception during the entire study treatment period and 90 days after the last dose of study treatment if their partner was of childbearing potential, even if they had a successful vasectomy, AND * Must have also adhered to the guidelines of the RevAssist program (US participants), RevAid program (Canadian participants), iAccess program (Australian participants), RevMate program (Japanese participants) or The Lenalidomide Pregnancy Risk Minimisation Plan as outlined in the study Manual (all other participants who were not using commercial supplies) 9. Must have been able to take concurrent aspirin 81 to 325 mg daily (or enoxaparin 40 mg subcutaneously daily \[or its equivalent\] if allergic to aspirin), per published standard or institutional standard of care, as prophylactic anticoagulation. NOTE: For participants with prior history of deep vein thrombosis (DVT), low-molecular-weight heparin (LMWH) was mandatory. 10. Voluntary written consent must have been given before performance of any study related procedure not part of standard medical care, with the understanding that consent may have been withdrawn by the participant at any time without prejudice to future medical care. 11. Was willing and able to adhere to the study visit schedule and other protocol requirements. Exclusion Criteria: 1. Was refractory to lenalidomide or proteasome inhibitor-based therapy at any line. NOTE: Refractory disease was defined as disease progression on treatment or progression within 60 days after the last dose of a given therapy. Participants who progressed after 60 days from the last dose of a given therapy were considered relapsed and were eligible for inclusion in the study. Participants who were refractory to thalidomide-based therapy were eligible. 2. Female participants who were breast feeding or pregnant. 3. Failure to have fully recovered (ie, Grade 1 toxicity) from the effects of prior chemotherapy (except for alopecia) regardless of the interval since last treatment. 4. Major surgery within 14 days before randomization. 5. Radiotherapy within 14 days before randomization. 6. Central nervous system involvement. 7. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before randomization. 8. Diagnosis of Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome. 9. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within 6 months before randomization in the study. 10. Systemic treatment with strong inhibitors of cytochrome P450 (CYP) 1A2 (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 within 14 days before randomization in the study. 11. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus positive. 12. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (eg, peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause). 13. Psychiatric illness/social situation that would limit compliance with study requirements. 14. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. 15. Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal condition that could interfere with the oral absorption or tolerance of treatment. 16. Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type were not excluded if they had undergone complete resection.