Trial Outcomes & Findings for Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Participants With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation (SCT) (NCT NCT03748953)

Last Updated: 2025-03-21

Results Overview

ECOG PS was used to assess physical health of participants. ECOG PS grade:0= fully active, able to carry on all pre-disease performance without restriction,1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature 2= ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours, 3= capable of only limited self-care, 4= completely disabled, cannot carry on any selfcare, totally confined to bed or chair confined to bed or chair more than 50% of waking hours and 5= dead. Only those categories with non-zero values were reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

37 participants

Primary outcome timeframe

Month 25

Results posted on

2025-03-21

Participant Flow

A total of 37 participants (31 enrolled in this study and 6 rolled over from study C16021\[NCT02312258\]) with a diagnosis of newly diagnosed multiple myeloma (NDMM) not treated with stem cell transplantation (SCT) took part in the study at investigative sites in China from 24 January 2019 to 06 December 2023.

Of the 31 participants who newly enrolled in this study, 10 (4 randomized to placebo and 6 to ixazomib) were enrolled before the implementation of Protocol Amendment 08, and 21 under the amendment, with all 21 receiving ixazomib as the study design was changed to a single-arm study. After Amendment 08, 2 of the 4 participants who were initially randomized to placebo crossed over to the ixazomib arm. As per planned analysis, these 4 participants were not included in the Efficacy Population.

Participant milestones

Participant milestones
Measure	Ixazomib Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).	Placebo Participants received ixazomib placebo-matching capsules, orally, once on Days 1, 8, and 15 of each cycle until Protocol Amendment 08 was implemented (cycle length=28 days).
Treatment Prior to Amendment 08 STARTED	6	4
Treatment Prior to Amendment 08 Placebo Safety Population	0	4
Treatment Prior to Amendment 08 COMPLETED	6	0
Treatment Prior to Amendment 08 NOT COMPLETED	0	4
Treatment Post Amendment 08 STARTED	35	0
Treatment Post Amendment 08 Efficacy Population	33	0
Treatment Post Amendment 08 Ixazomib Safety Population	35	0
Treatment Post Amendment 08 COMPLETED	0	0
Treatment Post Amendment 08 NOT COMPLETED	35	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ixazomib Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).	Placebo Participants received ixazomib placebo-matching capsules, orally, once on Days 1, 8, and 15 of each cycle until Protocol Amendment 08 was implemented (cycle length=28 days).
Treatment Prior to Amendment 08 Discontinued to Switch to Ixazomib	0	2
Treatment Prior to Amendment 08 Reason not Specified	0	2
Treatment Post Amendment 08 Withdrawal by Subject	18	0
Treatment Post Amendment 08 Reason not Specified	16	0
Treatment Post Amendment 08 Lost to Follow-up	1	0

Baseline Characteristics

Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Participants With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation (SCT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ixazomib n=33 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Age, Continuous	65.80 years STANDARD_DEVIATION 7.551 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	33 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 25

Population: Ixazomib Safety Population (ISP) included all participants who received at least 1 dose of ixazomib. As prespecified in the SAP, the ISP contained only one arm i.e., Ixazomib (participants originally randomized to ixazomib + participants who were randomized to the placebo arm prior to implementation of Amendment 08 and who crossed over to ixazomib arm contributing data for this outcome measure from the time they initiated ixazomib onward), thus data is presented accordingly.

Outcome measures

Outcome measures
Measure	Ixazomib n=35 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Number of Participants Categorized According to Performance Status (PS) Based on Eastern Cooperative Oncology Group (ECOG) PS ECOG Score 0	34 Participants
Number of Participants Categorized According to Performance Status (PS) Based on Eastern Cooperative Oncology Group (ECOG) PS ECOG Score 1	1 Participants

PRIMARY outcome

Timeframe: Up to 58.4 months

Population: ISP included all participants who received at least 1 dose of ixazomib. As prespecified in the SAP, the ISP contained only one arm i.e., Ixazomib (participants originally randomized to ixazomib + participants who were randomized to the placebo arm prior to implementation of Amendment 08 and who crossed over to ixazomib arm contributing data for this outcome measure from the time they initiated ixazomib onward), thus data is presented accordingly.

Adverse events (AEs) were defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug. A TEAE was defined as an AE that started or worsened after first study drug administration and within 30 days of last dose of study drug. Percentages are rounded off to the nearest whole number.

Outcome measures

Outcome measures
Measure	Ixazomib n=35 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Percentage of Participants Receiving Ixazomib With Treatment-emergent Adverse Events (TEAEs)	97 percentage of participants

PRIMARY outcome

Timeframe: Up to 58.4 months

AEs were defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug. A TEAE was defined as an AE that started or worsened after first study drug administration and within 30 days of last dose of study drug. An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital abnormality or birth defect, or is an important medical event. Percentages are rounded off to the nearest whole number.

Outcome measures

Outcome measures
Measure	Ixazomib n=35 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Percentage of Participants Receiving Ixazomib With Treatment-emergent Serious Adverse Events (SAEs)	31 percentage of participants

PRIMARY outcome

Timeframe: Up to 58.4 months

Clinical laboratory assessments included hematology, serum chemistry, and urinalysis. Any clinically significant changes in the clinical laboratory value over time based on the investigator's interpretation were reported.

Outcome measures

Outcome measures
Measure	Ixazomib n=35 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Number of Participants Receiving Ixazomib With Clinically Significant Changes in Safety Laboratory Values	0 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug to every 4 weeks until PD or death from any cause (up to 58.4 months)

Population: Efficacy Population included all participants who received ixazomib treatment for the duration of their study participation. As prespecified in the SAP, the Efficacy Population contained only one arm i.e., Ixazomib (efficacy outcomes data for the participants who received placebo before Protocol Amendment 8 was not collected per statistical analysis plan), thus data is presented accordingly.

PFS was defined as the time from the date of first dose of study drug to the first occurrence of PD as evaluated by the investigator or death from any cause, whichever occurred first. PD was defined as ≥25% increase from lowest value in serum M component or urine M-component; difference between involved and uninvolved free light chain (FLC) levels (absolute increase \>10 milligrams per deciliter \[mg/dL\]); bone marrow plasma cell percent ≥10%; new bone lesions or soft tissue plasmacytomas development or definite increase in existing bone lesions/soft tissue plasmacytomas size; hypercalcaemia development.

Outcome measures

Outcome measures
Measure	Ixazomib n=33 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Progression-Free Survival (PFS)	21.3 months Interval 9.2 to Upper limit of 95% confidence interval (CI) was not estimable due to censoring.

SECONDARY outcome

Timeframe: From the first dose of study drug to every 12 weeks during follow-up after PD or next line therapy or death whichever occurred later (up to 58.4 months)

OS was measured as the time from the date of first dose of study drug to the date of death.

Outcome measures

Outcome measures
Measure	Ixazomib n=33 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Overall Survival (OS)	NA months Median, lower limit, and upper limit of 95% CI were not estimable due to censoring.

SECONDARY outcome

Timeframe: Up to 58.4 months

Population: Response-evaluable Population included a subset of the Efficacy Population and consisted of all participants who had a baseline\&at least 1 postbaseline response assessment. As prespecified in the SAP, this population contained only one arm i.e., Ixazomib (efficacy outcomes data for the participants who received placebo before Protocol Amendment 8 was not collected per SAP), thus data is presented accordingly.

Response was assessed according to International Myeloma Working Group (IMWG) criteria. Best response includes partial response (PR), very good partial response (VGPR), and complete response (CR). PR as per IMWG criteria is 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to less than (\<)200 mg per 24 hours. VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hours. CR is negative immunofixation of serum and urine and disappearance of soft tissue plasmacytomas and \<5% plasma cells in bone marrow. Percentages are rounded off to the nearest whole number.

Outcome measures

Outcome measures
Measure	Ixazomib n=33 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Percentage of Participants Who Achieved or Maintained Best Response Before PD or up to Subsequent Therapy CR	76 percentage of participants
Percentage of Participants Who Achieved or Maintained Best Response Before PD or up to Subsequent Therapy PR	3 percentage of participants
Percentage of Participants Who Achieved or Maintained Best Response Before PD or up to Subsequent Therapy VGPR	12 percentage of participants

SECONDARY outcome

Timeframe: Up to 58.4 months

Duration of CR was defined as the time from the date of first dose of study drug or the date of CR to the date of first documentation of PD. CR was defined as negative immunofixation on the serum and urine; soft tissue plasmacytomas disappearance; \<5% plasma cells (PCs) in bone marrow.

Outcome measures

Outcome measures
Measure	Ixazomib n=33 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Duration of Complete Response (CR)	NA months Interval 12.88 to Median and upper limit of 95% CI were not estimable due to censoring.

SECONDARY outcome

Timeframe: Up to 58.4 months

TTP was defined as the time from the date of first dose of study drug to the date of first documentation of PD. PD was defined as ≥25% increase from lowest value in serum M component or urine M-component; difference between involved and uninvolved FLC levels (absolute increase \>10 mg/dL); bone marrow plasma cell percent ≥10%; new bone lesions or soft tissue plasmacytomas development or definite increase in existing bone lesions/soft tissue plasmacytomas size; hypercalcaemia development.

Outcome measures

Outcome measures
Measure	Ixazomib n=33 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Time to Progression (TTP)	21.3 months Interval 9.2 to Upper limit of 95% CI was not estimable due to censoring.

SECONDARY outcome

Timeframe: Up to 58.4 months

TTNT was defined as the time from the date of first dose of study drug to the date of the first dose of next-line of antineoplastic therapy.

Outcome measures

Outcome measures
Measure	Ixazomib n=33 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Time to Next-Line Therapy (TTNT)	NA months Interval 24.48 to Median and upper limit of 95% CI were not estimable due to censoring.

SECONDARY outcome

Timeframe: Up to 58.4 months

Population: ISP=all participants who received atleast 1 dose of ixazomib. As prespecified in SAP,ISP had only 1 arm:Ixazomib (participants originally randomized to ixazomib + participants randomized to placebo arm prior to implementation of Amendment 08 \& crossed over to ixazomib arm contributing data for this OM from time they initiated ixazomib onward), thus data is presented accordingly.

Outcome measures

Outcome measures
Measure	Ixazomib n=35 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Percentage of Participants With A New Primary Malignancy	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Cycle 26 (cycle length=28 days)

Population: Efficacy Population included all participants who received ixazomib treatment for the duration of their study participation. Overall number of participants analyzed is the number of participants with data available for analyses. As prespecified in the SAP, the Efficacy Population contained only one arm i.e., Ixazomib (efficacy outcomes data for the participants who received placebo before Protocol Amendment 8 was not collected per SAP), thus data is presented accordingly.

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The change from baseline in GHS (EORTC QLQ-C30) score is presented. Participant responses to the question "How would you rate your overall health during the past week?" are scored on a 7-point scale (1=very poor to 7=excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall GHS.

Outcome measures

Outcome measures
Measure	Ixazomib n=11 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 as Measured by the Global Health Status (GHS)	-5.3 score on a scale Standard Deviation 15.49

SECONDARY outcome

Timeframe: Up to 58.4 months

Population: Efficacy Population included all participants who received ixazomib treatment for the duration of their study participation. Number analyzed is the number of participants with data available for analysis for the specified category. As prespecified in the SAP, the Efficacy Population contained only one arm i.e., Ixazomib (efficacy outcomes data for the participants who received placebo before Protocol Amendment 8 was not collected per SAP), thus data is presented accordingly.

Participant's frailty status is classified as fit, unfit, or frail on the basis of 4 components: age, the Charlson comorbidity scoring system without age weighting, the Katz index of independence in activities of daily living, and the Lawton instrumental activities of daily living scale. The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from the date of first dose of study drug to the first occurrence of PD as evaluated by the investigator.

Outcome measures

Outcome measures
Measure	Ixazomib n=33 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Correlation Between Frailty Status and PFS Frailty Status: Fit	NA months Interval 12.68 to Median and upper limit of 95% CI were not estimable due to censoring.
Correlation Between Frailty Status and PFS Frailty Status: Unfit	20.9 months Interval 0.89 to Upper limit of 95% CI was not estimable due to censoring.
Correlation Between Frailty Status and PFS Frailty Status: Frail	6.5 months Interval 6.18 to Upper limit of 95% CI was not estimable due to censoring.

SECONDARY outcome

Timeframe: Up to 58.4 months

Participant's frailty status is classified as fit, unfit, or frail on the basis of 4 components: age, the Charlson comorbidity scoring system without age weighting, the Katz index of independence in activities of daily living, and the Lawton instrumental activities of daily living scale. The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. OS was measured as the time from the date of first dose of study drug to the date of death.

Outcome measures

Outcome measures
Measure	Ixazomib n=33 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Correlation Between Frailty Status and OS Frailty Status: Fit	NA months Median, lower limit, and upper limit of 95% CI were not estimable due to censoring.
Correlation Between Frailty Status and OS Frailty Status: Unfit	NA months Median, lower limit, and upper limit of 95% CI were not estimable due to censoring.
Correlation Between Frailty Status and OS Frailty Status: Frail	NA months Median, lower limit, and upper limit of 95% CI were not estimable due to censoring.

SECONDARY outcome

Timeframe: Cycle 1 (1 and 4 hours post-dose Day 1, Days 8 and 15 pre-dose); Cycle 2 and 5 (Days 1 and 8 pre-dose) and Cycles 3, 4, 6 to 10 (Day 1 pre-dose) (cycle length=28 days)

Population: ISP=all participants who received atleast 1 dose of ixazomib. Number analyzed=participants with data available for analysis at specified time point. As prespecified in SAP, ISP had only 1 arm:Ixazomib (participants originally randomized to ixazomib + participants randomized to placebo arm prior to implementation of Amendment 08 \& crossed over to ixazomib arm contributing data for this OM from time they initiated ixazomib onward), thus data is presented accordingly.

Plasma concentrations of the complete hydrolysis product of ixazomib citrate (ixazomib) were measured using a validated liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay.

Outcome measures

Outcome measures
Measure	Ixazomib n=35 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Plasma Concentration of Ixazomib Cycle 8 Day 1: Pre-dose	3.28 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 64.7
Plasma Concentration of Ixazomib Cycle 9 Day 1: Pre-dose	3.7 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 31.3
Plasma Concentration of Ixazomib Cycle 1 Day 1: 1 Hour Post-dose	15.3 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 181
Plasma Concentration of Ixazomib Cycle 1 Day 1: 4 Hours Post-dose	16.6 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 94.4
Plasma Concentration of Ixazomib Cycle 1 Day 8: Pre-dose	2.25 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 51.5
Plasma Concentration of Ixazomib Cycle 1 Day 15: Pre-dose	4 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 53.6
Plasma Concentration of Ixazomib Cycle 2 Day 1: Pre-dose	2.92 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 46.8
Plasma Concentration of Ixazomib Cycle 2 Day 8: Pre-dose	4.37 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 42.5
Plasma Concentration of Ixazomib Cycle 3 Day 1: Pre-dose	3.15 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 41.9
Plasma Concentration of Ixazomib Cycle 4 Day 1: Pre-dose	3.16 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 59.4
Plasma Concentration of Ixazomib Cycle 5 Day 1: Pre-dose	3.25 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 42.1
Plasma Concentration of Ixazomib Cycle 5 Day 8: Pre-dose	5.29 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 36.9
Plasma Concentration of Ixazomib Cycle 6 Day 1: Pre-dose	3.58 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 41.3
Plasma Concentration of Ixazomib Cycle 7 Day 1: Pre-dose	4.04 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 48.5
Plasma Concentration of Ixazomib Cycle 10 Day 1: Pre-dose	2.99 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 37.6

SECONDARY outcome

Timeframe: Up to 58.4 months

Population: ISP=all participants who received atleast 1 dose of ixazomib. Overall number of participants analyzed=participants with PN events. As prespecified in SAP,ISP had only 1 arm:Ixazomib (participants originally randomized to ixazomib+participants randomized to placebo prior to Amendment 08 \&crossed over to ixazomib arm contributing data for this OM from time they initiated ixazomib onward),\& is presented accordingly.

PN is defined as the event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the medical dictionary for regulatory activities (MedDRA). A PN event was considered as resolved if its final outcome was resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. Time to resolution was defined as the time from the initial onset date (inclusive) to the resolution date for resolved events.

Outcome measures

Outcome measures
Measure	Ixazomib n=3 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Time to Resolution of Peripheral Neuropathy (PN) Events	24.0 days Interval 7.0 to Upper limit of 95% CI was not estimable due to censoring.

SECONDARY outcome

Timeframe: Up to 58.4 months

Population: ISP=all participants who received atleast 1 dose of ixazomib. Overall number of participants analyzed=participants with PN events. As prespecified in SAP,ISP had only 1 arm:Ixazomib (participants originally randomized to ixazomib + participants randomized to placebo arm prior to implementation of Amendment 08 \& crossed over to ixazomib arm contributing data for this OM from time they initiated ixazomib onward), thus data is presented accordingly.

PN is defined as the event in the high-level term of peripheral neuropathies NEC according to the MedDRA. A PN event is considered to be improved if the event improves from the maximum grade; that is, all the grades recorded after the maximum grade are less than the maximum grade. Time to improvement is defined as the time from the initial onset date (inclusive) of the maximum grade to the first onset date that the toxicity grade is below the maximum grade with no higher grade thereafter, or the resolution date, whichever occurs first.

Outcome measures

Outcome measures
Measure	Ixazomib n=3 Participants Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).
Time to Improvement of PN Events	8.0 days Interval 7.0 to Upper limit of 95% CI was not estimable due to censoring.

Adverse Events

Ixazomib

Serious events: 11 serious events

Other events: 33 other events

Deaths: 1 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ixazomib n=35 participants at risk Participants received ixazomib 3 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented progressive disease (PD) or intolerable toxicity, whichever occurred first (cycle length=28 days).	Placebo n=4 participants at risk Participants received ixazomib placebo-matching capsules, orally, once on Days 1, 8, and 15 of each cycle until Protocol Amendment 08 was implemented (cycle length=28 days).
Cardiac disorders Cardiac failure congestive	2.9% 1/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.
Eye disorders Cataract	2.9% 1/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.
General disorders Chest discomfort	2.9% 1/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.
Hepatobiliary disorders Cholelithiasis	2.9% 1/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.
Infections and infestations COVID-19	5.7% 2/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.
Infections and infestations Pneumonia	2.9% 1/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.
Injury, poisoning and procedural complications Femur fracture	2.9% 1/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.
Injury, poisoning and procedural complications Post procedural haemorrhage	2.9% 1/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.
Musculoskeletal and connective tissue disorders Periarthritis	2.9% 1/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	2.9% 1/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.
Nervous system disorders Cerebral infarction	2.9% 1/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.
Skin and subcutaneous tissue disorders Angioedema	2.9% 1/35 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.	0.00% 0/4 • Up to 58.4 months Ixazomib Safety Population included all participants who received at least 1 dose of ixazomib. Placebo Safety Population included all participants who received at least 1 dose of placebo. Adverse events are presented per treatment received during the course of the study.

Other adverse events

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place