Phase 2 Study to Evaluate the Oral Combination of Ixazomib (MLN9708) With Cyclophosphamide and Dexamethasone in Patients With Newly Diagnosed or Relapsed and/or Refractory Multiple Myeloma

Inclusion Criteria

Each participant with newly diagnosed multiple myeloma (NDMM) must meet all of the following inclusion criteria to be enrolled in the study:

• Adult male or female participants 18 years of age or older with a confirmed diagnosis of symptomatic multiple myeloma (MM) according to standard criteria.
• Participants for whom cyclophosphamide and dexamethasone treatment is appropriate and who are considered not eligible for high-dose therapy (HDT)-stem cell transplantation (SCT) for 1 or more of the following reasons:
• The participant is 65 years of age or older.
• The participant is less than 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT.

Each participant with relapsed and/or refractory multiple myeloma (RRMM) must meet all of the following inclusion criteria to be enrolled in the study:

• Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic MM either currently or at the time of initial diagnosis, according to standard criteria, and relapsed and/or refractory disease after 1 to 3 lines of prior therapy. A participant is considered to have refractory disease if disease progression occurred during the treatment period or within 60 days of receiving the last dose of a given therapy. A line of therapy is defined as 1 or more cycles of a single-agent or combination therapy or a sequence of planned treatments such as induction therapy followed by autologous stem cell transplantation (ASCT) and then maintenance therapy.
• No evidence of graft-versus-host disease for participants who have undergone prior allogeneic stem cell transplantation.

In addition, all participants (NDMM and RRMM) must meet all of the remaining criteria:

• Participants must have 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 assay: involved free light chain level ≥ 10 mg/dL (≥ 100 mg/L), provided that the serum free light chain ratio is abnormal.
• Participants must meet all of 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 are not allowed within 3 days prior to administration of the study drug.
• 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 (CrCL) ≥ 30 mL/min.
• Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
• Female participants who:
• are postmenopausal for at least 1 year before the screening visit, or
• are surgically sterile, or
• If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, or
• agree to practice true abstinence over the period previously described, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [ie, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.), and
• adhere to any treatment-specific pregnancy prevention guidelines for cyclophosphamide and dexamethasone.
• Male participants, even if surgically sterilized (ie, status post-vasectomy), who:
• agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, or
• agree to practice true abstinence over the period previously described, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and with