A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant

The investigational drug being tested in this study is called ixazomib citrate. Ixazomib
citrate is being tested to slow disease progression and improve overall survival in people
who have NDMM who have had any type of positive response to induction therapy followed by HDT
and ASCT. This study will look at the effect of ixazomib citrate has on the length of time
that participants are free of disease progression and their overall survival.

The study will enroll approximately 652 participants. Participants will be randomly assigned
(by chance, like flipping a coin) to one of the two treatment groups—which will remain
undisclosed to the patient and study doctor during the study (unless there is an urgent
medical need):

- Ixazomib citrate 3 mg

- Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has
no active ingredient All participants will be asked to take one capsule on Days 1, 8 and
15 of each 28-day cycle, for up to 26 cycles (approximately 24 months).

This multi-center trial will be conducted globally. The overall time to participate in this
study is up to 107 months. Participants will make 28 visits to the clinic during the
treatment period and will continue to make visits in the 4 follow-up periods (PFS, PD, PFS2,
and OS). Participants will be assessed for disease response and PD during the PFS Follow-up
period and undergo follow up every 4 weeks until the next line of therapy begins.
Participants who start the next line of therapy will enter the PFS2 Follow-up period. During
the PFS2 Follow-up period, follow-up will occur every 12 weeks until PD2 occurs. After
participants in the PFS2 Follow-up period have PD2 on next-line therapy, they enter the OS
Follow-up period. During the OS Follow-up period, follow-up will occur every 12 weeks until
death or termination of the study.

Inclusion Criteria:

1. Adult male or female participants 18 years or older with a confirmed diagnosis of
symptomatic multiple myeloma according to standard criteria.

2. Documented results of cytogenetics/ fluorescence in situ hybridization (FISH) obtained
at any time before transplant, and International Staging System (ISS) staging at the
time of diagnosis available.

3. Underwent standard of care induction therapy (induction therapy must include
proteasome inhibitor (PI) and/or immunomodulating drugs (IMiD)-based regimens as
primary therapy for multiple myeloma), followed by a single autologous stem cell
transplant (ASCT) with a high-dose melphalan (200 mg/m^2) conditioning regimen, within
12 months of diagnosis. Vincristine, Adriamycin [doxorubicin], and dexamethasone (VAD)
is not an acceptable induction therapy for this trial.

4. Started screening no earlier than 75 days after transplant, completed screening within
15 days, and randomized no later than 115 days after transplant.

5. Must have not received post-ASCT consolidation therapy.

6. Documented response to ASCT (PR, VGPR, CR/stringent complete response [sCR]) according
to IMWG criteria.

7. ECOG performance status of 0 to 2.

8. Female participants who:

- 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, AND

- Must also adhere to the guidelines of any treatment-specific pregnancy prevention
program, if applicable, 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 for the female partner] and
withdrawal are not acceptable methods of contraception.)

Male participants, even if surgically sterilized (ie, 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, AND

- Must also adhere to the guidelines of any treatment-specific pregnancy prevention
program, if applicable, 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 for the female partner] and
withdrawal are not acceptable methods of contraception.)

9. 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.

10. Suitable venous access for the study-required blood sampling.

11. Is willing and able to adhere to the study visit schedule and other protocol
requirements.

12. Must meet the following clinical laboratory criteria at study entry:

- Absolute neutrophil count (ANC) ≥ 1,000 per cubic milliliter (/mm^3) and platelet
count ≥ 75,000/mm^3. Platelet transfusions to help patients meet eligibility
criteria are not allowed within 3 days before randomization.

- Total bilirubin ≤ 1.5 * the upper limit of the normal range (ULN).

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 * ULN.

- Calculated creatinine clearance ≥ 30 milliliter per minute (mL/min).

Exclusion Criteria:

1. Multiple myeloma which has relapsed following primary therapy or is not responsive to
primary therapy. For this study, stable disease following ASCT will be considered
nonresponsive to primary therapy.

2. Double (tandem) ASCT.

3. Radiotherapy within 14 days before the first dose of study drug.

4. Diagnosed or treated for another malignancy within 5 years before randomization or
previously diagnosed with another malignancy with evidence of residual disease.
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, POEMS (polyneuropathy, organomegaly,
endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell
leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative
syndrome.

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

11. Systemic treatment with strong inhibitors of cytochrome P450s (CYP)1A2 (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.

12. Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV)
positive.

13. 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).

14. Psychiatric illness/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 60 days before the first dose of
the study drug regimen.