A Study to Evaluate the Efficacy and Safety of Ixazomib i... | NCT03416374

NCT03416374

ID	Type	Description	Link
U1111-1207-0061	Other Identifier	WHO
JapicCTI-183839	Registry Identifier	JapicCTI

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Combination Therapy + Ixazomib Therapy	Experimental	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 Drug: Bortezomib Drug: Carfilzomib Drug: Lenalidomide Drug: Dexamethasone

Name	Type	Description	Arm Group Labels	Other Names
Ixazomib	Drug	Ixazomib capsules	Combination Therapy + Ixazomib Therapy

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment	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.	Up to 12 months

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS) From the Start of Study Treatment	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.	Up to 39 months as a maximum

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Eligibility for Treatment Period I

Men and women of age 20 years or older at the time of enrollment.
Participants with RRMM.
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.
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
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.
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.
Participants must be registered with, and comply with, the guidelines of the lenalidomide management program.
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
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

Women who are nursing or pregnant.
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.
Participants with poorly controlled active thrombosis.
Participants who have participated in a clinical trial of ixazomib or have been treated with ixazomib.
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.
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).
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.
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.
Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade ≥2 peripheral neuropathy.
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.
Infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment into Treatment Period I.
Participants with central nervous system involvement.
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.
Psychiatric illness/social situation that would limit compliance with study requirements.
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
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.
Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade ≥2 peripheral neuropathy during Treatment Period I.
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.
Participants using potent CYP3A4 inducing agents (rifampicin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or gingko biloba or St. John's wort.
Participants with hypersensitivity to any of the IRd study medications, their analogs, or excipients contained in IRd.
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/Locations Module

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Kameda Medical Center		Kamogawa	Chiba		Japan
The Jikei University Kashiwa Hospital

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37341778	Derived	Abe Y, Sasaki M, Takezako N, Ito S, Suzuki K, Handa H, Chou T, Yoshida T, Mori I, Shinozaki T, Suzuki K. Efficacy and Safety of Ixazomib Plus Lenalidomide and Dexamethasone Following Injectable PI-Based Therapy in Relapsed/Refractory Multiple Myeloma. Ann Hematol. 2023 Sep;102(9):2493-2504. doi: 10.1007/s00277-023-05212-7. Epub 2023 Jun 21.

Label	URL
To obtain more information on the study, click here/on this link	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 30, 2019	May 22, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

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 Information

ID	Title	Description
BG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
BG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	OG00050.0(15.3 to 84.7) OG00148.7(34.7 to 62.9) OG00248.9(35.9 to 62.0)

Secondary

Overall Survival (OS) From the Start of Study Treatment

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.

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

Posted

Median

95% Confidence Interval

Months

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)

Secondary

PFS From the Start of Study Treatment

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.

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.

Posted

Median

95% Confidence Interval

Months

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)
OG002	[Overall]; Combination Therapy + Ixazomib Therapy

Secondary

Percentage of Participants Who Achieved VGPR or Better (CR + VGPR)

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.

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.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy

Secondary

Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR

MRD was measured by the flow cytometry method using bone marrow aspiration. Reported data were numbers of participants with MRD positive and negative in bone marrow in participants who achieved CR. MRD positive was categorized into three sensitivity levels with the numbers of cells counted (10^-4 to - Max; 10^-5 to 10^-4; 10^-6 to 10^-5). 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.

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.

Posted

Count of Participants

Participants

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy

Secondary

Percentage of Participants Who Achieve or Maintain Any Best Response

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.

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.

Posted

Number

Percentage of Participants

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001

Secondary

Overall Response Rate (ORR)

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.

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.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001

Secondary

Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment

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.

Posted

Number

95% Confidence Interval

Percentage of Participants

12 months

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)
OG002	[Overall]; 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)

Secondary

Duration of Response (DOR)

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.

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.

Posted

Median

95% Confidence Interval

Months

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy

Secondary

Time to Next Treatment (TTNT)

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

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.

Posted

Median

95% Confidence Interval

Months

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)
OG002	[Overall]; Combination Therapy + Ixazomib Therapy

Secondary

Duration of Therapy (DOT)

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

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.

Posted

Median

95% Confidence Interval

Months

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)
OG002	[Overall]; Combination Therapy + Ixazomib Therapy

Secondary

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)

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.

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.

Posted

Mean

Standard Deviation

Score on a Scale

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)

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)

Secondary

Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score

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.

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.

Posted

Mean

Standard Deviation

Score on a Scale

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)

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)

Secondary

Evaluation of Modified Quality-Adjusted Life-Years (QALYs)

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.

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.

Posted

Median

Full Range

Quality-Adjusted Life-Years

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)

Secondary

Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month

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.

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.

Posted

Number

Number of Events per Participants-Month

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)

Secondary

Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants

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.

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.

Posted

Mean

Standard Deviation

Days

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)

Secondary

Relative Dose Intensity (RDI)

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].

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.

Posted

Median

Full Range

Percent

Up to 39 months as a maximum

ID	Title	Description
OG000	[Overall]; 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)

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Bone Lesions (Bone Evaluation)

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.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)
OG002	[Overall]; 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)

Secondary

Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs)

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.

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.

Posted

Count of Participants

Participants

Up to 39 months as a maximum

ID	Title	Description
OG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)
OG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy	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)	0	6	3	6	6	6
EG001	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy	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)	2	39	14	39	31	39
EG002	[Overall]; 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)	2	45	17	45	37	45

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0011 affected39 at risk EG0021 affected45 at risk
Prinzmetal angina	Cardiac disorders	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0011 affected39 at risk EG0021 affected45 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0011 affected39 at risk EG0021 affected45 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0011 affected39 at risk EG0021 affected45 at risk
Pyrexia	General disorders	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0011 affected39 at risk EG0021 affected45 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0011 affected39 at risk EG0021 affected45 at risk
Pneumonia	Infections and infestations	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0015 affected39 at risk EG0025 affected45 at risk
Influenza	Infections and infestations	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0012 affected39 at risk EG0022 affected45 at risk
Gastroenteritis	Infections and infestations	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0011 affected39 at risk EG0021 affected45 at risk
Pneumonia bacterial	Infections and infestations	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0011 affected39 at risk EG0021 affected45 at risk
Compression fracture	Injury, poisoning and procedural complications	MedDRA/J version24.0	Systematic Assessment	EG0001 affected6 at risk EG0010 affected39 at risk EG0021 affected45 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA/J version24.0	Systematic Assessment	EG0001 affected6 at risk EG0010 affected39 at risk EG0021 affected45 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA/J version24.0	Systematic Assessment	EG0001 affected6 at risk EG0010 affected39 at risk EG0021 affected45 at risk
Tumour lysis syndrome	Metabolism and nutrition disorders	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0011 affected39 at risk EG0021 affected45 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA/J version24.0	Systematic Assessment	EG0001 affected6 at risk EG0010 affected39 at risk EG0021 affected45 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0012 affected39 at risk EG0022 affected45 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0011 affected39 at risk EG0021 affected45 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA/J version24.0	Systematic Assessment	EG0000 affected6 at risk EG0011 affected39 at risk EG0021 affected45 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA/J version24.0	Systematic Assessment	EG0001 affected6 at risk EG0013 affected39 at risk EG0024 affected45 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA/J version24.0	Systematic Assessment	EG0003 affected6 at risk EG00110 affected39 at risk EG00213 affected45 at risk
Constipation	Gastrointestinal disorders	MedDRA/J version24.0	Systematic Assessment	EG0001 affected6 at risk EG0013 affected39 at risk EG0024 affected45 at risk
Malaise	General disorders	MedDRA/J version24.0	Systematic Assessment	EG0001 affected6 at risk EG0013 affected39 at risk EG0024 affected45 at risk
Pyrexia	General disorders	MedDRA/J version24.0	Systematic Assessment	EG0001 affected6 at risk EG0013 affected39 at risk EG0024 affected45 at risk
Nasopharyngitis	Infections and infestations	MedDRA/J version24.0	Systematic Assessment	EG0002 affected6 at risk EG0012 affected39 at risk EG0024 affected45 at risk
White blood cell count decreased	Investigations	MedDRA/J version24.0	Systematic Assessment	EG0002 affected6 at risk EG0019 affected39 at risk EG00211 affected45 at risk
Platelet count decreased	Investigations	MedDRA/J version24.0	Systematic Assessment	EG0001 affected6 at risk EG0018 affected39 at risk EG0029 affected45 at risk
Neutrophil count decreased	Investigations	MedDRA/J version24.0	Systematic Assessment	EG0001 affected6 at risk EG0016 affected39 at risk EG0027 affected45 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA/J version24.0	Systematic Assessment	EG0003 affected6 at risk EG0010 affected39 at risk EG0023 affected45 at risk
Taste disorder	Nervous system disorders	MedDRA/J version24.0	Systematic Assessment	EG0002 affected6 at risk EG0011 affected39 at risk EG0023 affected45 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA/J version24.0	Systematic Assessment	EG0004 affected6 at risk EG0013 affected39 at risk EG0027 affected45 at risk

First MCP Posted Date

ID	Term
C548400	ixazomib
D000069286	Bortezomib
C524865	carfilzomib
D000077269	Lenalidomide
D003907	Dexamethasone

Ancestor Terms

ID	Term
D001897	Boronic Acids
D000148	Acids, Noncarboxylic
D000143	Acids
D007287	Inorganic Chemicals
D001896	Boron Compounds
D009930	Organic Chemicals
D011719	Pyrazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D010797	Phthalimides
D010795	Phthalic Acids
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D010881	Piperidones
D010880	Piperidines
D054833	Isoindoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated

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)

NA: data not available due to below the level of detection and insufficient number of participants with events.

Number of participants analyzed was one.