A Study of Ixazomib, Given With Dexamethasone in Adults With Multiple Myeloma

Inclusion Criteria:

1. Must have a confirmed diagnosis of multiple myeloma (MM) requiring therapy according to International Myeloma Working Group (IMWG) criteria.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
3. Must have had a relapse or progressive disease (PD) after having received 2 or more prior lines of systemic therapy. Note: A line of therapy is defined as 1 or more cycles of a planned treatment program; this may consist 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 (SCT), followed by maintenance is considered 1 line of therapy. Typically each line of therapy is separated by PD. Discussion with the medical monitor may help clarify the number of lines of therapy that a prospective study participant had.
4. Must be refractory to lenalidomide, defined as having received at least 2 consecutive cycles of lenalidomide as a single agent or within a lenalidomide-containing regimen and having had PD during treatment with or within 60 days after the last dose of lenalidomide. The starting dose of lenalidomide should have been 25 mg (or as low as 10 mg in the case of renal function impairment or other safety concern), and the final dose should have been a minimum of 10 mg.
5. Must have received at least 2 consecutive cycles of a bortezomib- or carfilzomib-containing regimen, and either:

   * Achieved at least a partial response (PR) and did not have PD during treatment with or within 60 days after the last dose of bortezomib or carfilzomib, OR
   * Had bortezomib and/or carfilzomib intolerance (defined as discontinuation because of drug-related adverse events \[AEs\] before completion of the planned treatment course) without PD before the start of the next regimen.
6. Must have measurable disease defined by:

   * Serum M-protein \>=1 g/dL (\>=10 g/L), OR
   * Urine M-protein \>=200 mg/24 hours and must have documented MM isotype by immunofixation (central laboratory).
7. Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) sampling.
8. Recovered (that is, less than or equal to \[\<=\] Grade 1 nonhematologic toxicity) from the reversible effects of prior anticancer therapy.
9. Must be willing and able to adhere to pomalidomide-related risk mitigation activities if randomized to the pom+dex arm (example, Risk Evaluation and Mitigation Strategies \[REMS\], pregnancy prevention programs).

Exclusion Criteria:

1. Prior allogenic bone marrow transplantation in any prior line of therapy or prior autologous SCT in the last prior line of therapy- unless the autologous SCT was performed a year or more before disease progression.
2. Diagnosed with or treated for another malignancy within 2 years before randomization, or previously diagnosed with another malignancy and have any evidence of residual, persistent, or recurrent disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
3. Diagnosis of smoldering MM, Waldenström's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
4. Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of any cause on clinical examination during the Screening period.
5. Treatment with any investigational products or with chimeric or fully human monoclonal antibodies within 30 days before randomization, systemic anticancer therapy or radiotherapy within 14 days before randomization (Note: "spot" radiation for areas of pain is permitted), and major surgery within 14 days before randomization.
6. Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of study therapy, including difficulty swallowing.
7. Serious infection requiring parenteral antibiotic therapy or any other serious infection within 14 days before randomization.
8. Central nervous system involvement with MM (by clinical symptoms and signs).
9. Ongoing or active systemic infection, known human immunodeficiency virus-ribonucleic acid (RNA) positive, known hepatitis B surface antigen seropositive, or known hepatitis C virus-RNA positive.
10. Systemic treatment with strong cytochrome P-450 3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort within 14 days before randomization.
11. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
12. History of severe cutaneous reactions, including hypersensitivity reactions such as Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), in the context of treatment with lenalidomide or thalidomide.