A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant
Condition: Multiple Myeloma; Autologous Stem Cell Transplant
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Ixazomib Citrate; Placebo
Intervention description: Ixazomib citrate capsules; Ixazomib citrate placebo-matching 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: 656.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy; Ixazomib citrate

Summary:

      The purpose of this study is to determine the effect of ixazomib citrate maintenance therapy
      on progression-free survival (PFS), compared to placebo, in participants with newly diagnosed
      multiple myeloma (NDMM) who have had a response (complete response [CR], very good partial
      response [VGPR], or partial response [PR]) to induction therapy followed by high-dose therapy
      (HDT) and autologous stem cell transplant (ASCT).
    

Eligibility criteria:

        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 (SOC) 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 participants 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 that 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 cytochrome P450 3A (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.