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

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03416374
• Collaborator: (none)
• Enrollment: 45
• Locations: 23
• Arm: 1
• Actual Duration (Months): 39.3
• Patients Per Site: 2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed and/or Refractory Multiple Myeloma	Drug: Ixazomib; Drug: Bortezomib; Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone	Phase 4

Detailed Description

The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have RRMM. This study will look at the effectiveness and safety of IRd in participants with RRMM previously receiving an injectable proteasome inhibitor-based therapy. This study consists of two treatment periods, Treatment Period I and Treatment Period II.

The study will enroll 47 patients. All participants will receive following treatment:

• Combination therapy with Bortezomib + Lenalidomide + Dexamethasone (VRd) or combination therapy with Carfilzomib + Lenalidomide + Dexamethasone (KRd), standard recommended dose according to the package insert of each drug, as Treatment Period I, followed by Combination therapy with Ixazomib 4.0 mg + Lenalidomide 25 mg + Dexamethasone 40 mg (IRd) as Treatment Period II

At start of this study, combination therapy of VRd or KRd will be decided by investigator as Treatment Period I after the baseline evaluations. After the start of Treatment Period I, a participant's eligibility for Treatment Period II is then determined 3 cycles. Participants who meet these eligibility criteria II subsequently continue into Treatment Period II and receive IRd.

This multi-center trial will be conducted in Japan. It is anticipated that the treatment phase of this study will last up to 39 months, including 18 months for enrollment. Participants will make multiple visits to the clinic in treatment period, and follow-up period including a follow-up assessment after last dose of study drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Single-Arm, Multicenter 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
• Actual Study Start Date: Feb 18, 2018
• Actual Primary Completion Date: May 28, 2021
• Actual Study Completion Date: May 28, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Combination Therapy + Ixazomib Therapy Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)

Drug: Ixazomib; Ixazomib capsules; Drug: Bortezomib; Bortezomib injections; Drug: Carfilzomib; Carfilzomib intravenous infusions; Drug: Lenalidomide; Lenalidomide capsules; Drug: Dexamethasone; Dexamethasone tablets

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment [Up to 12 months]

   PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved free light chain (FLC) levels increase >10 mg/dl or bone marrow plasma cell ≥10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia.

Secondary Outcome Measures

1. Overall Survival (OS) From the Start of Study Treatment [Up to 39 months as a maximum]

   OS was defined as the period from the first dose of treatment in Treatment Period I to the time when death (regardless of the cause of death) was confirmed. Participants who were still alive were censored at the last confirmed date of survival or the date of data cut-off, whichever was earlier.

2. PFS From the Start of Study Treatment [Up to 39 months as a maximum]

   PFS was defined as the period from the first dose of treatment in Treatment Period I to the time of confirmed PD or confirmed death (regardless of the cause of death), whichever is earlier. PFS was assessed by IMWG Criteria.

3. Percentage of Participants Who Achieved VGPR or Better (CR + VGPR) [Up to 39 months as a maximum]

   VGPR or better (CR + VGPR) were assessed by IMWG Criteria. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow.

4. Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR [Up to 39 months as a maximum]

   MRD was measured by the flow cytometry method using bone marrow aspiration. Reported data were numbers of participants with MRD positive for three categories of sensitivity level (10^-4 to - Max; 10^-5 to 10^-4; 10^-6 to 10^-5) and negative in bone marrow in participants who achieved CR. MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. If a participant is MRD-positive at their first evaluation and MRD-negative after re-examination, the participant will be considered to be MRD-negative. CR will be assessed by IMWG Criteria.

5. Percentage of Participants Who Achieve or Maintain Any Best Response [Up to 39 months as a maximum]

   Best response is defined as the cumulative numbers of participants who achieve each level of best response including PR, VGPR and CR assessed with IMWG Criteria, after each cycle of treatment. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow.

6. Overall Response Rate (ORR) [Up to 39 months as a maximum]

   ORR is defined as the percentage of participants who achieve a best response of PR or better including stringent complete response (sCR), VGPR and PR assessed with IMWG Criteria, after the start of the study treatment. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow.

7. Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment [12 months]

8. Duration of Response (DOR) [Up to 39 months as a maximum]

   DOR is defined as the time from the date of first documentation of response ≥PR to the date of first documentation of PD or death due to any cause. PR and PD will be assessed with IMWG Criteria. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow.

9. Time to Next Treatment (TTNT) [Up to 39 months as a maximum]

   TTNT is defined as the period from the start of study treatment Period I to the start of next line treatment.

10. Duration of Therapy (DOT) [Up to 39 months as a maximum]

    DOT is defined as the treatment duration of study drug at study treatment Period I.

11. Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) [Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)]

    EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale (Global Health Status). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.

12. Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score [Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)]

    EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening.

13. Evaluation of Modified Quality-Adjusted Life-Years (QALYs) [Up to 39 months as a maximum]

    Modified QALYs was calculated from the score of EORTC QLQ-C30. The health-related quality of life scale score of EORTC QLQ-C30 was converted into a utility value ranging from 0 (dead) to 1 (perfect health), and used to adjust the value of survival years; this value was assessed as the modified QALY.

14. Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month [Up to 39 months as a maximum]

    HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Number of events with hospitalization per participants-month in Treatment Period I and Treatment Period II was reported.

15. Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants [Up to 39 months as a maximum]

    HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Duration of hospital stay per participants in Treatment Period I and Treatment Period II was reported.

16. Relative Dose Intensity (RDI) [Up to 39 months as a maximum]

    RDI for each study drug is defined as 100*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals [dose prescribed at enrollment* number of prescribed doses per cycle* the number of treated cycles].

17. Percentage of Participants With Bone Lesions (Bone Evaluation) [Up to 39 months as a maximum]

18. Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs) [Up to 39 months as a maximum]

    An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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.

2. 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.

3. Participants must be registered with, and comply with, the guidelines of the lenalidomide management program.

4. 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

1. 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.

1. 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).

2. 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.

3. 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.

4. Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade ≥2 peripheral neuropathy.

5. 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.

6. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment into Treatment Period I.

7. Participants with central nervous system involvement.

8. 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.

9. Psychiatric illness/social situation that would limit compliance with study requirements.

10. 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

1. 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.

2. Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade ≥2 peripheral neuropathy during Treatment Period I.

3. 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.

4. Participants using potent CYP3A4 inducing agents (rifampicin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or gingko biloba or St. John's wort.

5. Participants with hypersensitivity to any of the IRd study medications, their analogs, or excipients contained in IRd.

6. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kameda Medical Center	Kamogawa	Chiba	Japan
2	The Jikei University Kashiwa Hospital	Kashiwa	Chiba	Japan
3	Ogaki Municipal Hospital	Ogaki	Gifu	Japan
4	Gunma University Hospital	Maebashi	Gunma	Japan
5	Shibukawa Medical Center	Shibukawa	Gunma	Japan
6	Kobe city Medical Center General Hospital	Kobe	Hyogo	Japan
7	Kanazawa University Hospital	Kanazawa	Ishikawa	Japan
8	Iwate Medical University	Morioka	Iwate	Japan
9	Yokohama Municipal Citizen's Hospital	Yokohama	Kanagawa	Japan
10	Suwa Red Cross Hospital	Suwa	Nagano	Japan
11	Dokkyo Medical University	Koshigaya	Saitama	Japan
12	Juntendo University Hospital	Bunkyo-ku	Tokyo	Japan
13	Nippon Medical School Hospital	Bunkyo-ku	Tokyo	Japan
14	Nihon University Itabashi Hospital	Itabashi-ku	Tokyo	Japan
15	The Cancer Institute Hospital of JFCR	Koto-ku	Tokyo	Japan
16	The Jikei University Hospital	Minato-ku	Tokyo	Japan
17	Kyorin University Hospital	Mitaka	Tokyo	Japan
18	Japanese Red Cross Medical Center	Shibuya-ku	Tokyo	Japan
19	Tokyo Disaster Medical Center	Tachikawa	Tokyo	Japan
20	Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital	Hiroshima		Japan
21	Kyoto Kuramaguchi Medical Center	Kyoto		Japan
22	Niigata Cancer Center Hospital	Niigata		Japan
23	Osaka Red Cross Hospital	Osaka		Japan

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - May 30, 2019
• Statistical Analysis Plan - Nov 1, 2021

More Information

Additional Information:

• To obtain more information on the study, click here/on this link

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03416374
• Other Study ID Numbers: C16043; U1111-1207-0061; JapicCTI-183839
• First Posted: Jan 31, 2018
• Last Update Posted: Aug 22, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Lenalidomide; Bortezomib; Ixazomib

Study Results

Participant Flow

Recruitment Details	Participant s took part in the survey at 33 investigative sites in Japan, from 18 February 2018 to 28 May 2021.
Pre-assignment Detail	A total of 45 participants were enrolled and received the study treatment in this study.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Period Title: Treatment Period I
STARTED	6	39
COMPLETED	0	0
NOT COMPLETED	6	39
Period Title: Treatment Period I
STARTED	6	39
COMPLETED	6	30
NOT COMPLETED	0	9
Period Title: Treatment Period I
STARTED	6	30
COMPLETED	2	12
NOT COMPLETED	4	18

Baseline Characteristics

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	Total
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Total of all reporting groups
Overall Participants	6	39	45
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	71.8 (8.57)	70.5 (9.40)	70.7 (9.21)
Sex: Female, Male (Count of Participants)
Female	5 83.3%	16 41%	21 46.7%
Male	1 16.7%	23 59%	24 53.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
Japan	6 100%	39 100%	45 100%
Height (Centimeters (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Centimeters (cm)]	153.0 (9.70)	158.5 (8.29)	157.8 (8.58)
Weight (Kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms (kg)]	52.85 (7.204)	57.87 (10.380)	57.17 (10.081)
BMI (Kilogram (kg)/meter (m)^2]) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilogram (kg)/meter (m)^2]]	22.60 (2.619)	22.91 (2.512)	22.86 (2.497)
Body Surface Area (m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m^2]	1.487 (0.1395)	1.583 (0.1760)	1.569 (0.1732)
International Staging System (at Initial Diagnosis) (Count of Participants)
Stage I	2 33.3%	17 43.6%	19 42.2%
Stage II	3 50%	14 35.9%	17 37.8%
Stage III	1 16.7%	8 20.5%	9 20%
International Staging System (at First Treatment [Period I]) (Count of Participants)
Stage I	5 83.3%	19 48.7%	24 53.3%
Stage II	1 16.7%	12 30.8%	13 28.9%
Stage III	0 0%	5 12.8%	5 11.1%
Missing	0 0%	3 7.7%	3 6.7%
Eastern Cooperative Oncology Group performance status (ECOG P.S.) (Count of Participants)
Scale = 0	4 66.7%	29 74.4%	33 73.3%
Scale = 1	2 33.3%	8 20.5%	10 22.2%
Scale = 2	0 0%	2 5.1%	2 4.4%
Scale = 3	0 0%	0 0%	0 0%
Scale = 4	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment
Description	PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved free light chain (FLC) levels increase >10 mg/dl or bone marrow plasma cell ≥10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Number (90% Confidence Interval) [Percentage of Participants]	50.0 833.3%	48.7 124.9%	48.9 108.7%

2. Secondary Outcome

Title	Overall Survival (OS) From the Start of Study Treatment
Description	OS was defined as the period from the first dose of treatment in Treatment Period I to the time when death (regardless of the cause of death) was confirmed. Participants who were still alive were censored at the last confirmed date of survival or the date of data cut-off, whichever was earlier.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Median (95% Confidence Interval) [Months]	NA	NA	NA

3. Secondary Outcome

Title	PFS From the Start of Study Treatment
Description	PFS was defined as the period from the first dose of treatment in Treatment Period I to the time of confirmed PD or confirmed death (regardless of the cause of death), whichever is earlier. PFS was assessed by IMWG Criteria.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Median (95% Confidence Interval) [Months]	NA	28.96	28.96

4. Secondary Outcome

Title	Percentage of Participants Who Achieved VGPR or Better (CR + VGPR)
Description	VGPR or better (CR + VGPR) were assessed by IMWG Criteria. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Number (95% Confidence Interval) [Percentage of Participants]	33.3 555%	43.6 111.8%	42.2 93.8%

5. Secondary Outcome

Title	Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR
Description	MRD was measured by the flow cytometry method using bone marrow aspiration. Reported data were numbers of participants with MRD positive for three categories of sensitivity level (10^-4 to - Max; 10^-5 to 10^-4; 10^-6 to 10^-5) and negative in bone marrow in participants who achieved CR. MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. If a participant is MRD-positive at their first evaluation and MRD-negative after re-examination, the participant will be considered to be MRD-negative. CR will be assessed by IMWG Criteria.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	2	9	11
Sensitivity Level; 10^-4=< - Max	0 0%	1 2.6%	1 2.2%
Sensitivity Level; 10^-5=< - <10^-4	1 16.7%	2 5.1%	3 6.7%
Sensitivity Level; 10^-6=< - <10^-5	1 16.7%	1 2.6%	2 4.4%
Negative	0 0%	5 12.8%	5 11.1%

6. Secondary Outcome

Title	Percentage of Participants Who Achieve or Maintain Any Best Response
Description	Best response is defined as the cumulative numbers of participants who achieve each level of best response including PR, VGPR and CR assessed with IMWG Criteria, after each cycle of treatment. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
CR	33.3 555%	23.1 59.2%	24.4 54.2%
VGPR	0 0%	20.5 52.6%	17.8 39.6%
PR	50.0 833.3%	28.2 72.3%	31.1 69.1%

7. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	ORR is defined as the percentage of participants who achieve a best response of PR or better including stringent complete response (sCR), VGPR and PR assessed with IMWG Criteria, after the start of the study treatment. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Number (95% Confidence Interval) [Percentage of Participants]	83.3 1388.3%	71.8 184.1%	73.3 162.9%

8. Secondary Outcome

Title	Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Number (95% Confidence Interval) [Percentage of Participants]	50.0 833.3%	35.9 92.1%	37.8 84%

9. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR is defined as the time from the date of first documentation of response ≥PR to the date of first documentation of PD or death due to any cause. PR and PD will be assessed with IMWG Criteria. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level <100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	5	28	33
Median (95% Confidence Interval) [Months]	15.31	28.03	28.03

10. Secondary Outcome

Title	Time to Next Treatment (TTNT)
Description	TTNT is defined as the period from the start of study treatment Period I to the start of next line treatment.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Median (95% Confidence Interval) [Months]	21.59	32.26	32.26

11. Secondary Outcome

Title	Duration of Therapy (DOT)
Description	DOT is defined as the treatment duration of study drug at study treatment Period I.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Median (95% Confidence Interval) [Months]	14.69	12.43	12.43

12. Secondary Outcome

Title	Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
Description	EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale (Global Health Status). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.
Time Frame	Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Baseline	44.44 (40.369)	63.25 (24.085)	60.74 (26.981)
Cycle 23	0 (NA)	54.17 (8.740)	46.43 (21.973)
Cycle 32	50.00 (23.750)	50.00 (23.750)

13. Secondary Outcome

Title	Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score
Description	EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening.
Time Frame	Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Disease Symptoms: Baseline	24.07 (21.564)	19.23 (16.756)	19.88 (17.266)
Disease Symptoms: Cycle 23	0 (NA)	4.63 (7.384)	3.97 (6.964)
Disease Symptoms: Cycle 32	2.78 (3.928)	2.78 (3.928)
Side-Effects of Treatment: Baseline	16.67 (12.776)	16.60 (14.464)	16.61 (14.115)
Side-Effects of Treatment: Cycle 23	3.70 (NA)	16.05 (3.825)	14.29 (5.828)
Side-Effects of Treatment: Cycle 32	18.52 (15.713)	18.52 (15.713)
Body Image: Baseline	44.44 (45.542)	23.08 (26.660)	25.93 (30.058)
Body Image: Cycle 23	0 (NA)	16.67 (18.257)	14.29 (17.817)
Body Image: Cycle 32	16.67 (23.570)	16.67 (23.570)
Future Perspective: Baseline	66.67 (37.185)	44.16 (24.114)	47.16 (26.817)
Future Perspective: Cycle 23	11.11 (NA)	35.19 (8.364)	31.75 (11.878)
Future Perspective: Cycle 32	27.78 (7.857)	27.78 (7.857)

14. Secondary Outcome

Title	Evaluation of Modified Quality-Adjusted Life-Years (QALYs)
Description	Modified QALYs was calculated from the score of EORTC QLQ-C30. The health-related quality of life scale score of EORTC QLQ-C30 was converted into a utility value ranging from 0 (dead) to 1 (perfect health), and used to adjust the value of survival years; this value was assessed as the modified QALY.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	4	16	20
Median (Full Range) [Quality-Adjusted Life-Years]	0.467	0.534	0.518

15. Secondary Outcome

Title	Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month
Description	HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Number of events with hospitalization per participants-month in Treatment Period I and Treatment Period II was reported.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Number [Number of Events per Participants-Month]	1.9 31.7%	2.9 7.4%	2.7 6%

16. Secondary Outcome

Title	Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants
Description	HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Duration of hospital stay per participants in Treatment Period I and Treatment Period II was reported.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Mean (Standard Deviation) [Days]	14.8 (16.01)	19.4 (18.14)	18.8 (17.77)

17. Secondary Outcome

Title	Relative Dose Intensity (RDI)
Description	RDI for each study drug is defined as 100*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals [dose prescribed at enrollment* number of prescribed doses per cycle* the number of treated cycles].
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	45
Bortezomib, Ixazomib	71.93
Carfilzomib, Ixazomib	87.70
Bortezomib/Carfilzomib, Ixazomib	83.24
Lenalidomide	47.18
Dexamethasone	48.61

18. Secondary Outcome

Title	Percentage of Participants With Bone Lesions (Bone Evaluation)
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Number (95% Confidence Interval) [Percentage of Participants]	100.0 1666.7%	59.1 151.5%	64.0 142.2%

19. Secondary Outcome

Title	Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs)
Description	An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame	Up to 39 months as a maximum

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Measure Participants	6	39	45
Count of Participants [Participants]	6 100%	35 89.7%	41 91.1%

Adverse Events

Time Frame	Up to 39 months as a maximum
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events (AEs) and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
Arm/Group Title	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy		[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy		[Overall]; Combination Therapy + Ixazomib Therapy
Arm/Group Description	Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)		Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)		Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
All Cause Mortality
	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy		[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy		[Overall]; Combination Therapy + Ixazomib Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		2/39 (5.1%)		2/45 (4.4%)
Serious Adverse Events
	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy		[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy		[Overall]; Combination Therapy + Ixazomib Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		14/39 (35.9%)		17/45 (37.8%)
Blood and lymphatic system disorders
Febrile neutropenia	0/6 (0%)		1/39 (2.6%)		1/45 (2.2%)
Cardiac disorders
Prinzmetal angina	0/6 (0%)		1/39 (2.6%)		1/45 (2.2%)
Gastrointestinal disorders
Duodenal ulcer	0/6 (0%)		1/39 (2.6%)		1/45 (2.2%)
Enterocolitis	0/6 (0%)		1/39 (2.6%)		1/45 (2.2%)
General disorders
Pyrexia	0/6 (0%)		1/39 (2.6%)		1/45 (2.2%)
Hepatobiliary disorders
Bile duct stone	0/6 (0%)		1/39 (2.6%)		1/45 (2.2%)
Infections and infestations
Pneumonia	0/6 (0%)		5/39 (12.8%)		5/45 (11.1%)
Influenza	0/6 (0%)		2/39 (5.1%)		2/45 (4.4%)
Gastroenteritis	0/6 (0%)		1/39 (2.6%)		1/45 (2.2%)
Pneumonia bacterial	0/6 (0%)		1/39 (2.6%)		1/45 (2.2%)
Injury, poisoning and procedural complications
Compression fracture	1/6 (16.7%)		0/39 (0%)		1/45 (2.2%)
Spinal compression fracture	1/6 (16.7%)		0/39 (0%)		1/45 (2.2%)
Tibia fracture	1/6 (16.7%)		0/39 (0%)		1/45 (2.2%)
Metabolism and nutrition disorders
Tumour lysis syndrome	0/6 (0%)		1/39 (2.6%)		1/45 (2.2%)
Musculoskeletal and connective tissue disorders
Bone pain	1/6 (16.7%)		0/39 (0%)		1/45 (2.2%)
Renal and urinary disorders
Acute kidney injury	0/6 (0%)		2/39 (5.1%)		2/45 (4.4%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	0/6 (0%)		1/39 (2.6%)		1/45 (2.2%)
Skin and subcutaneous tissue disorders
Rash	0/6 (0%)		1/39 (2.6%)		1/45 (2.2%)
Other (Not Including Serious) Adverse Events
	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy		[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy		[Overall]; Combination Therapy + Ixazomib Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		31/39 (79.5%)		37/45 (82.2%)
Blood and lymphatic system disorders
Anaemia	1/6 (16.7%)		3/39 (7.7%)		4/45 (8.9%)
Gastrointestinal disorders
Diarrhoea	3/6 (50%)		10/39 (25.6%)		13/45 (28.9%)
Constipation	1/6 (16.7%)		3/39 (7.7%)		4/45 (8.9%)
General disorders
Malaise	1/6 (16.7%)		3/39 (7.7%)		4/45 (8.9%)
Pyrexia	1/6 (16.7%)		3/39 (7.7%)		4/45 (8.9%)
Infections and infestations
Nasopharyngitis	2/6 (33.3%)		2/39 (5.1%)		4/45 (8.9%)
Investigations
White blood cell count decreased	2/6 (33.3%)		9/39 (23.1%)		11/45 (24.4%)
Platelet count decreased	1/6 (16.7%)		8/39 (20.5%)		9/45 (20%)
Neutrophil count decreased	1/6 (16.7%)		6/39 (15.4%)		7/45 (15.6%)
Metabolism and nutrition disorders
Decreased appetite	3/6 (50%)		0/39 (0%)		3/45 (6.7%)
Nervous system disorders
Taste disorder	2/6 (33.3%)		1/39 (2.6%)		3/45 (6.7%)
Skin and subcutaneous tissue disorders
Rash	4/6 (66.7%)		3/39 (7.7%)		7/45 (15.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.