A Study to Evaluate the Efficacy and Safety of Ixazomib in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma Initially Treated With an Injection of Proteasome Inhibitor-Based Therapy
Condition: Relapsed and/or Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Ixazomib; Bortezomib; Carfilzomib; Lenalidomide; Dexamethasone
Intervention description: Ixazomib capsules; Bortezomib injections; Carfilzomib intravenous infusions; Lenalidomide capsules; Dexamethasone tablets
Intervention MeSH terms: Dexamethasone; Lenalidomide; Bortezomib; Ixazomib
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to investigate the efficacy and safety of long-term
      administration of the oral proteasome inhibitor ixazomib as part of ixazomib in combination
      with lenalidomide and dexamethasone (IRd) therapy in patients with relapsed and/or refractory
      multiple myeloma (RRMM) treated initially with an injectable proteasome inhibitor-based
      therapy.
    

Eligibility criteria:

        Inclusion Criteria:

        Eligibility for Treatment Period I

          1. Men and women of age 20 years or older at the time of enrollment.

          2. Participants with RRMM.

          3. Participants who are planned to start combination therapy with bortezomib,
             lenalidomide, and dexamethasone (VRd) or carfilzomib, lenalidomide, and dexamethasone
             (KRd) as second, third or fourth line of treatment.

          4. Participants with measurable disease defined by one or more of the following three
             measurements.

               -  Serum M-protein: ≥0.5 gram (g)/ deciliter (dL) (≥ 5 g/ liter [L])

               -  Urine M-protein: ≥ 200 milligram (mg)/24 hours

               -  Serum free light chain assay: involved free light chain concentration ≥ 10 mg/dL
                  (≥ 100 mg/L) provided that the serum free light chain ratio is abnormal

          5. Participants with Eastern Cooperative Oncology Group (ECOG) performance status (PS)
             0-2; however, participants with ECOG PS 3 are eligible if they only have symptoms
             associated with bone lesions.

          6. Participants who are considered by the principal investigator or investigator not to
             be eligible for transplant; or, if considered eligible for transplant, participants
             who are planned not to undergo transplant for at least 12 months after the start of
             the study treatment.

          7. Participants must be registered with, and comply with, the guidelines of the
             lenalidomide management program.

          8. Participants who, before implementing procedures related to clinical research
             (excluding standard medical practices), understand that they can withdraw consent at
             any time without suffering from disadvantages to future treatments, and can provide
             written informed consent.

             Eligibility for Treatment Period II

          9. Participants must have received an injectable proteasome inhibitor (bortezomib or
             carfilzomib) in each treatment cycle of Treatment Period I.

        Exclusion Criteria:

        Eligibility for Treatment Period I

          1. Women who are nursing or pregnant.

          2. Participants with another active malignancy, i.e. synchronous active malignancy or
             previous malignancy with a disease-free period of less than 5 years, except for
             participants with carcinoma in situ (intraepithelial carcinoma) or intramucosal
             carcinoma judged to be cured by topical treatment.

          3. Participants with poorly controlled active thrombosis.

          4. Participants who have participated in a clinical trial of ixazomib or have been
             treated with ixazomib.

          5. Participants who were refractory to either treatment regimen based on lenalidomide
             and/or proteasome inhibitor(s).

             Note: Refractory MM is defined as PD on therapy or PD within 60 days after the last
             dose of a given therapy. Participants who have disease progressed 60 days after the
             last dose of a given therapy will be considered as relapsed in this study.

          6. Participants with ongoing or active systemic infection, known hepatitis B virus
             infection, known hepatitis C virus infection, or known positivity to human
             immunodeficiency virus (HIV).

          7. Participants who underwent major surgery within 14 days prior to enrollment to
             Treatment Period I. Surgery for bone lesions is not considered as major surgery.

          8. Participants who received radiation therapy within 14 days prior to enrollment to
             Treatment Period I. If the radiation field is small, 7 days is considered as a
             sufficient interval between radiation therapy and chemotherapy.

          9. Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or
             Grade ≥2 peripheral neuropathy.

         10. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled
             hypertension, uncontrolled cardiac arrhythmia, symptomatic congestive heart failure,
             unstable angina, or myocardial infarction within the past 6 months before enrollment
             to Treatment Period I.

         11. Infection requiring systemic antibiotic therapy or other serious infection within 14
             days before enrollment into Treatment Period I.

         12. Participants with central nervous system involvement.

         13. Inability to swallow oral medications, inability or unwillingness to comply with the
             drug administration requirements, or gastrointestinal conditions that could interfere
             with the oral absorption or tolerance of treatment.

         14. Psychiatric illness/social situation that would limit compliance with study
             requirements.

         15. 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.

             Eligibility for Treatment Period II

         16. Participants who do not achieve at least a minimal response (MR) to VRd or KRd in
             Treatment Period I per the International Myeloma Working Group (IMWG) response
             criteria, 2014 revision.

         17. Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or
             Grade ≥2 peripheral neuropathy during Treatment Period I.

         18. Participants with evidence of uncontrolled cardiovascular conditions, including
             uncontrolled hypertension, uncontrolled cardiac arrhythmia, symptomatic congestive
             heart failure, unstable angina, or myocardial infarction during Treatment Period I.

         19. Participants using potent CYP3A4 inducing agents (rifampicin, rifapentine, rifabutin,
             carbamazepine, phenytoin, phenobarbital), or gingko biloba or St. John's wort.

         20. Participants with hypersensitivity to any of the IRd study medications, their analogs,
             or excipients contained in IRd.

         21. 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.