Trial Outcomes & Findings for Phase 2 Study to Evaluate the Oral Combination of Ixazomib (MLN9708) With Cyclophosphamide and Dexamethasone in Patients With Newly Diagnosed or Relapsed and/or Refractory Multiple Myeloma (NCT NCT02046070)

NCT ID: NCT02046070

Last Updated: 2019-07-17

Results Overview

Combined Response Rate is the percentage of participants with Complete Response (CR), including stringent Complete Response (sCR), and Very Good Partial Response (VGPR) according to the International Myeloma Working Group (IMWG) criteria during the Induction Phase (Cycles 1-13, 28-day cycles). CR=negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component \<100 mg/24 hour.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

148 participants

Primary outcome timeframe

Day 1 of Cycles 1-13, 28-day cycles (Up to 1 year)

Results posted on

2019-07-17

Participant Flow

Participants took part in the study at 23 investigative sites in Australia, Greece, Poland, Sweden and the United States from 05 March 2014 to 29 June 2018.

Participants with NDMM were enrolled in 1 of 2 arms to receive 4.0 mg ixazomib in combination with 300 or 400 mg cyclophosphamide and 40 mg dexamethasone (CCd); participants with RRMM were enrolled in 1 arm to receive ixazomib 4.0 mg CCd. All arms included a safety lead-in cohort for pharmacokinetics (PK) analysis.

Participant milestones

Participant milestones
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle until PD/death or unacceptable toxicity in participants with RRMM.
Overall Study STARTED	36	34	78
Overall Study COMPLETED	4	6	8
Overall Study NOT COMPLETED	32	28	70

Reasons for withdrawal

Reasons for withdrawal
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle until PD/death or unacceptable toxicity in participants with RRMM.
Overall Study Progressive Disease	18	11	40
Overall Study Adverse Event	8	10	17
Overall Study Withdrawal by Subject	1	2	6
Overall Study Study Terminated by Sponsor	1	1	1
Overall Study Reason not Specified	4	4	6

Baseline Characteristics

Number Analyzed is the number of participants with data available for analysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=36 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=34 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM) n=78 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle until PD/death or unacceptable toxicity in participants with RRMM.	Total n=148 Participants Total of all reporting groups
Age, Continuous	73.4 years STANDARD_DEVIATION 5.48 • n=36 Participants	74.1 years STANDARD_DEVIATION 5.80 • n=34 Participants	63.5 years STANDARD_DEVIATION 9.85 • n=78 Participants	68.3 years STANDARD_DEVIATION 9.59 • n=148 Participants
Sex: Female, Male Female	21 Participants n=36 Participants	16 Participants n=34 Participants	37 Participants n=78 Participants	74 Participants n=148 Participants
Sex: Female, Male Male	15 Participants n=36 Participants	18 Participants n=34 Participants	41 Participants n=78 Participants	74 Participants n=148 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=36 Participants	0 Participants n=34 Participants	0 Participants n=78 Participants	1 Participants n=148 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=36 Participants	33 Participants n=34 Participants	75 Participants n=78 Participants	143 Participants n=148 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=36 Participants	1 Participants n=34 Participants	3 Participants n=78 Participants	4 Participants n=148 Participants
Race/Ethnicity, Customized White	35 Participants n=36 Participants	34 Participants n=34 Participants	74 Participants n=78 Participants	143 Participants n=148 Participants
Race/Ethnicity, Customized Other	1 Participants n=36 Participants	0 Participants n=34 Participants	2 Participants n=78 Participants	3 Participants n=148 Participants
Race/Ethnicity, Customized Asian	0 Participants n=36 Participants	0 Participants n=34 Participants	1 Participants n=78 Participants	1 Participants n=148 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=36 Participants	0 Participants n=34 Participants	1 Participants n=78 Participants	1 Participants n=148 Participants
Height	163.5 centimeters (cm) STANDARD_DEVIATION 11.35 • n=36 Participants • Number Analyzed is the number of participants with data available for analysis.	163.5 centimeters (cm) STANDARD_DEVIATION 12.47 • n=34 Participants • Number Analyzed is the number of participants with data available for analysis.	165.9 centimeters (cm) STANDARD_DEVIATION 10.47 • n=77 Participants • Number Analyzed is the number of participants with data available for analysis.	164.8 centimeters (cm) STANDARD_DEVIATION 11.16 • n=147 Participants • Number Analyzed is the number of participants with data available for analysis.
Weight	73.6 kilograms (kg) STANDARD_DEVIATION 11.8 • n=36 Participants	73.0 kilograms (kg) STANDARD_DEVIATION 17.54 • n=34 Participants	78.1 kilograms (kg) STANDARD_DEVIATION 16.80 • n=78 Participants	75.8 kilograms (kg) STANDARD_DEVIATION 15.99 • n=148 Participants
Body Surface Area (BSA)	1.8 meters squared (m^2) STANDARD_DEVIATION 0.17 • n=36 Participants	1.8 meters squared (m^2) STANDARD_DEVIATION 0.26 • n=34 Participants	1.9 meters squared (m^2) STANDARD_DEVIATION 0.23 • n=78 Participants	1.8 meters squared (m^2) STANDARD_DEVIATION 0.23 • n=148 Participants

PRIMARY outcome

Timeframe: Day 1 of Cycles 1-13, 28-day cycles (Up to 1 year)

Population: Response Evaluable Population was defined as participants who received at least 2 of the 3 ixazomib doses during Cycle 1, had measurable disease at Baseline, and at least 1 postbaseline response assessment.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=33 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=34 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Combined Response Rate During the Induction Phase in Newly Diagnosed Multiple Myeloma (NDMM) Participants	27 percentage of participants Interval 13.0 to 46.0	24 percentage of participants Interval 11.0 to 41.0

PRIMARY outcome

Timeframe: Day 1 of each 28 day cycle (Up to 45 months)

ORR is the percentage of participants with CR, VGPR or PR according to IMWG criteria. CR=negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas and \<5% plasma cells (PC) in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component \<100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or \<200 mg/24 hour or decrease 50% difference between involved free light chain (FLC) levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=73 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Overall Response Rate (ORR) in Relapsed and/or Refractory Multiple Myeloma (RRMM) Participants	49 percentage of participants Interval 37.0 to 61.0	—

SECONDARY outcome

Timeframe: First dose of study drug through 30 days after last dose of drug (Up to 45 months)

Population: Safety Population was defined as all participants who receive at least 1 dose of any study drug.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug was determined by the Investigator.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=36 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=34 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Number of Participants With Adverse Events (AEs), Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction and Serious Adverse Events (SAEs) in NDMM Participants Any AE	35 Participants	34 Participants
Number of Participants With Adverse Events (AEs), Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction and Serious Adverse Events (SAEs) in NDMM Participants Grade 3 or Higher AEs	27 Participants	27 Participants
Number of Participants With Adverse Events (AEs), Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction and Serious Adverse Events (SAEs) in NDMM Participants AEs Resulting in Treatment Discontinuation	9 Participants	11 Participants
Number of Participants With Adverse Events (AEs), Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction and Serious Adverse Events (SAEs) in NDMM Participants AEs Resulting in Dose Reduction	11 Participants	10 Participants
Number of Participants With Adverse Events (AEs), Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction and Serious Adverse Events (SAEs) in NDMM Participants SAEs	17 Participants	20 Participants

SECONDARY outcome

Timeframe: Day 1 of Cycles 1-13, 28-day cycles (Up to 1 year)

Percentage of participants with CR + VGPR + PR (ORR), CR, VGPR, PR, SD, PD according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;\<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component \<100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or \<200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas. SD=not meeting criteria for VGPR, PR or PD. PD=25% increase in lowest value any of the following: serum M-component, urine M-component, difference between involved and uninvolved FLC levels, bone marrow PC percentage; new or increase in size of existing bone lesions or soft tissue plasmacytomas.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=33 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=34 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase CR + VGPR + PR	79 percentage of participants Interval 61.0 to 91.0	71 percentage of participants Interval 53.0 to 85.0
Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase CR	12 percentage of participants Interval 3.0 to 28.0	9 percentage of participants Interval 2.0 to 24.0
Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase VGPR	15 percentage of participants Interval 5.0 to 32.0	15 percentage of participants Interval 5.0 to 31.0
Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase PR	67 percentage of participants Interval 48.0 to 82.0	62 percentage of participants Interval 44.0 to 78.0
Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase SD	12 percentage of participants Interval 3.0 to 28.0	18 percentage of participants Interval 7.0 to 35.0
Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase PD	0 percentage of participants Interval 0.0 to 0.0	3 percentage of participants Interval 1.0 to 15.0

SECONDARY outcome

Timeframe: Day 1 of each 28-day Cycle (Up to 45 months)

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=33 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=34 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants PD	0 percentage of participants Interval 0.0 to 0.0	6 percentage of participants Interval 1.0 to 20.0
Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants CR + VGPR + PR	82 percentage of participants Interval 65.0 to 93.0	71 percentage of participants Interval 53.0 to 85.0
Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants CR + VGPR	36 percentage of participants Interval 20.0 to 55.0	32 percentage of participants Interval 17.0 to 51.0
Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants CR	15 percentage of participants Interval 5.0 to 32.0	12 percentage of participants Interval 3.0 to 27.0
Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants VGPR	21 percentage of participants Interval 9.0 to 39.0	21 percentage of participants Interval 9.0 to 38.0
Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants PR	67 percentage of participants Interval 48.0 to 82.0	59 percentage of participants Interval 41.0 to 75.0
Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants SD	18 percentage of participants Interval 7.0 to 35.0	18 percentage of participants Interval 7.0 to 35.0

SECONDARY outcome

Timeframe: Up to 1 year

Population: Participants from the Response Evaluable Population, defined as participants who received at least 2 of the 3 ixazomib doses during Cycle 1, had measurable disease at Baseline, and at least 1 postbaseline response assessment, who responded.

TTR is defined as the time interval from the date of the first dose of study treatment to the date of the first documented confirmed response of PR or better up to the initiation of alternative therapy in a participant who responded.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=26 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=23 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Time to Response (TTR) in NDMM Participants During the Induction Phase	2.2 months Interval 0.95 to 2.92	1.9 months Interval 0.95 to 1.9

SECONDARY outcome

Timeframe: Up to 45 Months

Population: Participants from the Response Evaluable Population, participants who received at least 2 of the 3 ixazomib doses during Cycle 1, had measurable disease at Baseline and at least 1 postbaseline response assessment, who responded. Responders without PD were censored at the date of SD or better prior to the date of alternative therapy.

DOR is defined as the time from the date of first documentation of a confirmed PR or better to the date of first documented PD up to the initiation of alternative therapy.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=26 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=23 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Duration of Response (DOR) in NDMM Participants	32.2 months Interval 18.66 to 95% Confidence Interval (CI) Upper Limit was not estimable due to the low number of participants with events.	36.6 months Interval 19.75 to 95% CI Upper Limit was not estimable due to the low number of participants with events.

SECONDARY outcome

Timeframe: Up to 45 months

Population: Safety Population was defined as all participants who received at least 1 dose of any study drug. Participants without documentation of PD were censored at the date of last response assessment that is SD or better prior to the date of the alternative therapy.

TTP is defined as the time from the date of first dose of study treatment to the date of first documentation of disease progression.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=36 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=34 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Time to Progression (TTP) in NDMM Participants	30.9 months Interval 19.58 to 41.66	32.2 months Interval 20.27 to 95% CI Upper Limit was not estimable due to the low number of participants with events.

SECONDARY outcome

Timeframe: Up to 45 months

Population: Safety Population was defined as all participants who received at least 1 dose of any study drug. Participants without documentation of PD or death were censored at the date of last response assessment that is SD or better prior to the date of the alternative therapy.

PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression or death.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=36 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=34 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Progression Free Survival (PFS) in NDMM Participants	23.5 months Interval 15.67 to 39.59	23.0 months Interval 15.9 to 95% CI Upper Limit was not estimable due to the low number of participants with events.

SECONDARY outcome

Timeframe: First dose of study drug through 30 days after the last dose of drug (Up to 45 months)

Population: Safety Population was defined as all participants who receive at least 1 dose of any study drug. Number of participants analyzed is the number of participants who remained on treatment after 13 cycles.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=24 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=22 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Number of Participants With AEs, SAEs, AEs Resulting in Discontinuation and AEs Resulting in Dose Reduction in NDMM Participants Remaining on Treatment After 13 Cycles Any AE	22 Participants	20 Participants
Number of Participants With AEs, SAEs, AEs Resulting in Discontinuation and AEs Resulting in Dose Reduction in NDMM Participants Remaining on Treatment After 13 Cycles SAE	6 Participants	4 Participants
Number of Participants With AEs, SAEs, AEs Resulting in Discontinuation and AEs Resulting in Dose Reduction in NDMM Participants Remaining on Treatment After 13 Cycles AEs Resulting in Treatment Discontinuation	1 Participants	2 Participants
Number of Participants With AEs, SAEs, AEs Resulting in Discontinuation and AEs Resulting in Dose Reduction in NDMM Participants Remaining on Treatment After 13 Cycles AEs Resulting in Dose Reduction	5 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline (BL) (Day 1 of Cycle 1), Day 1 of Cycle 13 (Up to 1 year)

Population: Participants from the Safety Population, defined as all participants who received at least 1 dose of any study drug, with data available for analysis.

EORTC QLQ-C30 is a patient completed 30 item questionnaire that consists of 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The patient evaluates their health status over the previous week. There are 28 questions answered on a 4-point scale where1=Not at all (best) to 4=Very Much (worst) and 2 questions answered on a 7-point scale where 1=Very poor (worst) to 7= Excellent (best). All of the scales and single-item measures are transformed to a score:0 to 100. For functioning scales and global QOL higher scores indicate better functioning (a positive change from Baseline indicates improvement); for symptom scales higher scores indicate more severe symptoms (a negative change from Baseline indicates improvement).

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=24 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=23 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Cognitive functioning, Change from BL at Cycle 13	2.78 score on a scale Standard Deviation 22.877	-7.25 score on a scale Standard Deviation 14.058
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Social functioning, Change from BL at Cycle 13	9.03 score on a scale Standard Deviation 39.921	-11.59 score on a scale Standard Deviation 29.914
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Fatigue, Change from BL at Cycle 13	-10.88 score on a scale Standard Deviation 35.307	-6.76 score on a scale Standard Deviation 30.473
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Nausea/Vomiting, Change from BL at Cycle 13	-4.86 score on a scale Standard Deviation 26.228	-4.35 score on a scale Standard Deviation 19.603
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Pain, Change from BL at Cycle 13	-13.89 score on a scale Standard Deviation 52.628	-10.87 score on a scale Standard Deviation 39.443
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Dyspnea, Change from BL at Cycle 13	-11.11 score on a scale Standard Deviation 37.644	-7.25 score on a scale Standard Deviation 40.147
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Insomnia, Change from BL at Cycle 13	-16.67 score on a scale Standard Deviation 46.104	-10.14 score on a scale Standard Deviation 35.441
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Appetite Loss, Change from BL at Cycle 13	-18.06 score on a scale Standard Deviation 42.822	-7.25 score on a scale Standard Deviation 24.529
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Physical functioning, Change from BL at Cycle 13	14.17 score on a scale Standard Deviation 35.675	17.97 score on a scale Standard Deviation 20.640
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Role functioning, Change from BL at Cycle 13	8.33 score on a scale Standard Deviation 43.127	6.52 score on a scale Standard Deviation 35.441
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Emotional functioning, Change from BL at Cycle 13	11.34 score on a scale Standard Deviation 27.837	2.54 score on a scale Standard Deviation 15.977
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Constipation, Change from BL at Cycle 13	-13.89 score on a scale Standard Deviation 39.215	-5.80 score on a scale Standard Deviation 41.013
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Diarrhea, Change from BL at Cycle 13	-2.78 score on a scale Standard Deviation 30.954	5.80 score on a scale Standard Deviation 19.207
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Financial Difficulties, Change from BL at Cycle 13	4.17 score on a scale Standard Deviation 26.580	1.45 score on a scale Standard Deviation 30.942
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) During the Induction Phase in NDMM Participants Global Health Status/QoL, Change from BL; Cycle 13	3.47 score on a scale Standard Deviation 30.783	-5.43 score on a scale Standard Deviation 24.180

SECONDARY outcome

Timeframe: Day 1 of each 28-day Cycle (Up to 45 months)

Percentage of participants with Overall Response (CR + VGPR + PR), CR, VGPR and PR according to IMWG criteria. CR=negative immunofixation of serum and urine; disappearance of soft tissue plasmacytomas;\<5% PC in bone marrow. VGPR=serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% reduction in serum M-component plus urine M-component \<100 mg/24 hour. PR=50% reduction of serum M-protein and reduction in 24 hour urine M-protein by 90% or \<200 mg/24 hour or decrease 50% difference between involved FLC levels or 50% reduction in bone marrow plasma cells if baseline percentage was 30%; and if present at Baseline, 50% reduction in the size of soft tissue plasmacytomas.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=24 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=21 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Percentage of Participants With CR + VGR + PR (ORR), CR, VGPR, and PR in NDMM Participants Remaining on Treatment After 13 Cycles CR + VGPR + PR	75.0 percentage of participants	85.7 percentage of participants
Percentage of Participants With CR + VGR + PR (ORR), CR, VGPR, and PR in NDMM Participants Remaining on Treatment After 13 Cycles CR	16.7 percentage of participants	19.0 percentage of participants
Percentage of Participants With CR + VGR + PR (ORR), CR, VGPR, and PR in NDMM Participants Remaining on Treatment After 13 Cycles VGPR	20.8 percentage of participants	28.6 percentage of participants
Percentage of Participants With CR + VGR + PR (ORR), CR, VGPR, and PR in NDMM Participants Remaining on Treatment After 13 Cycles PR	37.5 percentage of participants	38.1 percentage of participants

SECONDARY outcome

Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

Population: PK-Evaluable Population was defined as participants in the safety lead-in cohort who have sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters. Number analyzed is the number of participants with data available for analysis at the given time-point.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=6 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=6 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Cmax: Maximum Observed Plasma Concentration for Ixazomib in NDMM Participants Cycle 1 Day 1	64.283 nanogram/mL (ng/mL) Standard Deviation 36.283	46.600 nanogram/mL (ng/mL) Standard Deviation 34.7722
Cmax: Maximum Observed Plasma Concentration for Ixazomib in NDMM Participants Cycle 1 Day 15	53.145 nanogram/mL (ng/mL) Standard Deviation 46.3782	62.280 nanogram/mL (ng/mL) Standard Deviation 39.4249

SECONDARY outcome

Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=6 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=6 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Tmax: Time to First Occurrence of Cmax for Ixazomib in NDMM Participants Cycle 1 Day 1	1.250 hour (hr) Interval 0.92 to 1.58	1.040 hour (hr) Interval 0.5 to 2.0
Tmax: Time to First Occurrence of Cmax for Ixazomib in NDMM Participants Cycle 1 Day 15	1.000 hour (hr) Interval 0.45 to 4.0	1.000 hour (hr) Interval 0.5 to 1.5

SECONDARY outcome

Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=6 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) n=6 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in NDMM Participants Cycle 1 Day 1	885.167 hr*ng/mL Standard Deviation 354.1465	792.600 hr*ng/mL Standard Deviation 650.5665
AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in NDMM Participants Cycle 1 Day 15	1338.333 hr*ng/mL Standard Deviation 746.2902	1226.600 hr*ng/mL Standard Deviation 527.5792

SECONDARY outcome

Timeframe: First dose of study drug through 30 days after last dose of drug (Up to 45 months)

Population: Safety population was defined as all participants who received at least 1 dose of any study drug.

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug was determined by the Investigator.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=78 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Number of Participants With AEs, Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction, SAEs in RRMM Participants Grade 3 or Higher AE	49 Participants	—
Number of Participants With AEs, Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction, SAEs in RRMM Participants Any AE	72 Participants	—
Number of Participants With AEs, Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction, SAEs in RRMM Participants AEs Resulting in Treatment Discontinuation	19 Participants	—
Number of Participants With AEs, Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction, SAEs in RRMM Participants AEs Resulting in Dose Reduction	30 Participants	—
Number of Participants With AEs, Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction, SAEs in RRMM Participants SAEs	30 Participants	—

SECONDARY outcome

Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=7 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Cmax: Maximum Observed Plasma Concentration for Ixazomib in RRMM Participants Cycle 1 Day 1	47.400 ng/mL Standard Deviation 36.7083	—
Cmax: Maximum Observed Plasma Concentration for Ixazomib in RRMM Participants Cycle 1 Day 15	52.229 ng/mL Standard Deviation 39.6006	—

SECONDARY outcome

Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168) hours postdose

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=7 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Tmax: Time to First Occurrence of Cmax for Ixazomib in RRMM Participants Cycle 1 Day 1	1.225 hr Interval 0.5 to 3.42	—
Tmax: Time to First Occurrence of Cmax for Ixazomib in RRMM Participants Cycle 1 Day 15	2.000 hr Interval 0.5 to 8.0	—

SECONDARY outcome

Timeframe: Cycle 1 Days 1 and 15 predose and at multiple timepoints (up to 168 hours) postdose

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=7 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in RRMM Participants Cycle 1 Day 1	518.167 hr*ng/mL Standard Deviation 78.8274	—
AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in RRMM Participants Cycle 1 Day 15	1241.000 hr*ng/mL Standard Deviation 657.4978	—

SECONDARY outcome

Timeframe: Day 1 of each 28-day Cycle (Up to 45 months)

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=73 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants CR + VGPR	19 percentage of participants Interval 11.0 to 30.0	—
Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants CR	5 percentage of participants Interval 2.0 to 13.0	—
Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants VGPR	14 percentage of participants Interval 7.0 to 24.0	—
Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants PR	44 percentage of participants Interval 32.0 to 56.0	—
Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants SD	37 percentage of participants Interval 26.0 to 49.0	—
Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants PD	10 percentage of participants Interval 4.0 to 19.0	—

SECONDARY outcome

Timeframe: Up to 45 months

TTR is defined as the time interval from the date of the first dose of study treatment to the date of the first documented confirmed response of PR or better up to the alternative therapy in a participant who responded.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=36 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Time to Response (TTR) in RRMM Participants	2.1 months Interval 0.95 to 3.12	—

SECONDARY outcome

Timeframe: Up to 45 months

DOR is defined as the time from the date of first documentation of a confirmed PR or better to the date of first documented PD up to the alternative therapy.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=36 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Duration of Response (DOR) in RRMM Participants	26.3 months Interval 12.22 to 95% CI Upper Limit was not estimable due to the low number of participants with events.	—

SECONDARY outcome

Timeframe: Up to 45 months

TTP is defined as the time from the date of first dose of study treatment to the date of first documentation of disease progression.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=78 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Time to Progression (TTP) in RRMM Participants	16.8 months Interval 11.3 to 24.67	—

SECONDARY outcome

Timeframe: Up to 45 months

Population: Safety Population was defined as all participants who received at least 1 dose of any study drug. Participants without documentation of PD or death were censored at the date of last response assessment that was SD or better prior to the date of the alternative therapy.

PFS is defined as the time from the date of first dose of study treatment to the date of the first documented disease progression or death.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=78 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Progression Free Survival (PFS) in RRMM Participants	14.2 months Interval 9.69 to 20.57	—

SECONDARY outcome

Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of End of Treatment (EOT) (Up to 45 months)

Population: Participants from the Safety Population, defined as all participants who received at least 1 dose of any study drug, with data available for analysis.

Outcome measures

Outcome measures
Measure	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) n=50 Participants Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 300 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.	Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until PD/death or unacceptable toxicity \[13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months\] and cyclophosphamide (CYC) 400 mg/m\^2, tablets, orally, on Days 1, 8 and 15 of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity and dexamethasone (DEX) 40 mg, tablets, orally, on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients \>75 years) of a 28-day cycle for 13 cycles or until PD/death or unacceptable toxicity in participants with NDMM.
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Global Health Status/QoL, Change from BL at EOT	-5.50 score on a scale Standard Deviation 20.798	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Physical functioning, Change from BL at EOT	-6.00 score on a scale Standard Deviation 19.806	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Role functioning, Change from BL at EOT	-7.67 score on a scale Standard Deviation 30.344	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Emotional functioning, Change from BL at EOT	-5.00 score on a scale Standard Deviation 23.023	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Cognitive functioning, Change from BL at EOT	-5.33 score on a scale Standard Deviation 19.760	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Social functioning, Change from BL at EOT	-11.33 score on a scale Standard Deviation 26.177	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Fatigue, Change from BL at EOT	5.11 score on a scale Standard Deviation 22.695	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Nausea/Vomiting, Change from BL at EOT	3.33 score on a scale Standard Deviation 14.677	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Pain, Change from BL at EOT	5.00 score on a scale Standard Deviation 28.621	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Dyspnea, Change from BL at EOT	10.00 score on a scale Standard Deviation 27.970	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Insomnia, Change from BL at EOT	-6.00 score on a scale Standard Deviation 27.512	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Appetite Loss, Change from BL at EOT	4.67 score on a scale Standard Deviation 24.290	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Constipation, Change from BL at EOT	2.00 score on a scale Standard Deviation 18.332	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Diarrhea, Change from BL at EOT	6.00 score on a scale Standard Deviation 19.852	—
Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants Financial Difficulties, Change from BL at EOT	4.00 score on a scale Standard Deviation 20.909	—

Adverse Events

Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)

Serious events: 17 serious events

Other events: 34 other events

Deaths: 3 deaths

Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)

Serious events: 20 serious events

Other events: 34 other events

Deaths: 2 deaths

Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)

Serious events: 30 serious events

Other events: 69 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Publication restrictions are in place

Restriction type: OTHER