A Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Placebo; Ixazomib
Intervention description: Ixazomib placebo-matching capsules.; Ixazomib capsules.
Intervention MeSH terms: Ixazomib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 706.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to determine the effect of ixazomib maintenance therapy on
      progression free survival (PFS) compared with placebo, in participants with NDMM who have had
      a major response (complete response [CR], very good partial response [VGPR], or partial
      response [PR]) to initial therapy and who have not undergone SCT.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult male or female participants 18 years or older with a confirmed diagnosis of
             symptomatic newly diagnosed multiple myeloma (NDMM) according to standard criteria.

          2. Completed 6 to 12 months (± 2 weeks) of initial therapy, during which the participant
             was treated to best response, defined as the best response maintained for 2 cycles
             after the M-protein nadir is reached.

          3. Documented major response (PR, VGPR, CR) according to the International Myeloma
             Working Group (IMWG) uniform response criteria, version 2011, after this initial
             therapy.

          4. 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, when this is in line with the preferred and
                  usual lifestyle of the participant. (Periodic abstinence [eg, calendar,
                  ovulation, symptothermal, postovulation methods] and withdrawal are not
                  acceptable methods of contraception.)

             Male participants, even if surgically sterilized (that is, status postvasectomy), 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, when this is in line with the preferred and
                  usual lifestyle of the participant. (Periodic abstinence [example, calendar,
                  ovulation, symptothermal, postovulation methods for the female partner] and
                  withdrawal are not acceptable methods of contraception.)

          5. Voluntary written consent must be given before performance of any study-related
             procedure not part of standard medical care, with the understanding that consent may
             be withdrawn by the participant at any time without prejudice to future medical care.

          6. Complete documentation of the details of the initial therapy before randomization
             including cytogenetics and International Staging System (ISS) is available.

          7. Eastern Cooperative Oncology Group Performance Status of 0 to 2.

          8. Suitable venous access for the study-required blood sampling and consent for the
             specific amounts that will be taken.

          9. Is willing and able to adhere to the study visit schedule and other protocol
             requirements including blood sampling and bone marrow aspiration.

         10. Must meet the following clinical laboratory criteria at study entry:

               -  Absolute neutrophil count (ANC) greater than or equal to (≥) 1,000 per cubic
                  millimeter (/mm^3) without growth factor support and platelet count ≥75,000/mm^3.
                  Platelet transfusions to help participants meet eligibility criteria are not
                  allowed within 3 days before randomization.

               -  Total bilirubin less than or equal to (≤) 1.5*the upper limit of the normal range
                  (ULN).

               -  Alanine aminotransferase and aspartate aminotransferase ≤ 3*ULN.

               -  Calculated creatinine clearance ≥ 30 milliliter per minute (mL/min) (using the
                  Cockcroft-Gault equation).

        Exclusion Criteria:

          1. Multiple myeloma that has relapsed after, or was not responsive to, initial therapy.

          2. Prior SCT.

          3. Radiotherapy within 14 days before randomization.

          4. Diagnosed or treated for another malignancy within 5 years before randomization or
             previous diagnosis with another malignancy. Participants with nonmelanoma skin cancer
             or carcinoma in situ of any type are not excluded if they have undergone complete
             resection.

          5. Female participants who are lactating and breastfeeding or have a positive serum
             pregnancy test during the Screening period.

          6. Major surgery within 14 days before randomization.

          7. Central nervous system involvement.

          8. Infection requiring intravenous (IV) antibiotic therapy or other serious infection
             within 14 days before randomization.

          9. Diagnosis of Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly,
             endocrinopathy, monoclonal gammopathy, and skin changes syndrome (POEMS), plasma cell
             leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative
             syndrome.

         10. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled
             hypertension, uncontrolled cardiac arrhythmias, uncontrolled congestive heart failure,
             unstable angina, or myocardial infarction within the past 6 months.

         11. Systemic treatment with strong cytochrome P450 3A (CYP3A) inducers (rifampin,
             rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or St. John's wort
             within 14 days before randomization.

         12. Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active
             hepatitis B or C infection.

         13. Comorbid systemic illnesses or other severe concurrent disease that, 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 (example, PN that is Grade 1 with pain or Grade 2 or higher of
             any cause).

         14. Psychiatric illness or social situation that would limit compliance with study
             requirements.

         15. Known allergy to any of the study medications, their analogues, or excipients in the
             various formulations of any agent.

         16. Inability to swallow oral medication, inability or unwillingness to comply with the
             drug administration requirements, or gastrointestinal (GI) procedure that could
             interfere with the oral absorption or tolerance of treatment.

         17. Treatment with any investigational products within 30 days before randomization.