Phase 2 Study to Evaluate the Oral Combination of Ixazomi... | NCT02046070

ID	Type	Description	Link
2013-003113-17	EudraCT Number
U1111-1158-2714	Registry Identifier	WHO

Label	Type	Description	Intervention Names
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM)	Experimental	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.	Drug: Cyclophosphamide Drug: Ixazomib Drug: Dexamethasone
Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM)	Experimental	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.	Drug: Cyclophosphamide Drug: Ixazomib Drug: Dexamethasone
Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)	Experimental	Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle and cyclophosphamide 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.

Name	Type	Description	Arm Group Labels	Other Names
Cyclophosphamide	Drug	Cyclophosphamide tablets	Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Combined Response Rate During the Induction Phase in Newly Diagnosed Multiple Myeloma (NDMM) Participants	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.	Day 1 of Cycles 1-13, 28-day cycles (Up to 1 year)
Overall Response Rate (ORR) in Relapsed and/or Refractory Multiple Myeloma (RRMM) Participants	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.	Day 1 of each 28 day cycle (Up to 45 months)

Secondary Outcomes

Measure	Description	Time Frame
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	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Each participant with newly diagnosed multiple myeloma (NDMM) must meet all of the following inclusion criteria to be enrolled in the study:

Adult male or female participants 18 years of age or older with a confirmed diagnosis of symptomatic multiple myeloma (MM) according to standard criteria.
Participants for whom cyclophosphamide and dexamethasone treatment is appropriate and who are considered not eligible for high-dose therapy (HDT)-stem cell transplantation (SCT) for 1 or more of the following reasons:
- The participant is 65 years of age or older.
- The participant is less than 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT.

Each participant with relapsed and/or refractory multiple myeloma (RRMM) must meet all of the following inclusion criteria to be enrolled in the study:

Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic MM either currently or at the time of initial diagnosis, according to standard criteria, and relapsed and/or refractory disease after 1 to 3 lines of prior therapy. A participant is considered to have refractory disease if disease progression occurred during the treatment period or within 60 days of receiving the last dose of a given therapy. A line of therapy is defined as 1 or more cycles of a single-agent or combination therapy or a sequence of planned treatments such as induction therapy followed by autologous stem cell transplantation (ASCT) and then maintenance therapy.
No evidence of graft-versus-host disease for participants who have undergone prior allogeneic stem cell transplantation.

In addition, all participants (NDMM and RRMM) must meet all of the remaining criteria:

Participants must have measurable disease defined by at least 1 of the following 3 measurements:
- Serum M-protein ≥ 1 g/dL (≥ 10 g/L).
- Urine M-protein ≥ 200 mg/24 hours.
- Serum free light chain assay: involved free light chain level ≥ 10 mg/dL (≥ 100 mg/L), provided that the serum free light chain ratio is abnormal.
Participants must meet all of the following clinical laboratory criteria:
- Absolute neutrophil count (ANC) ≥ 1000/mm^3 and platelet count ≥ 75,000/mm^3. Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days prior to administration of the study drug.
- Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
- Calculated creatinine clearance (CrCL) ≥ 30 mL/min.
Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
Female participants who:
- are postmenopausal for at least 1 year before the screening visit, or
- are surgically sterile, or
- If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, or
- agree to practice true abstinence over the period previously described, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [ie, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.), and
- adhere to any treatment-specific pregnancy prevention guidelines for cyclophosphamide and dexamethasone.
Male participants, even if surgically sterilized (ie, status post-vasectomy), who:
- agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, or
- agree to practice true abstinence over the period previously described, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.), and
- adhere to any treatment-specific pregnancy prevention guidelines for cyclophosphamide and dexamethasone.
Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
Suitable venous access for the study-required blood sampling.
Is willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen (for participants with NDMM only).

NOTE: Prior treatment with corticosteroids (maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone over 14 days. Localized radiation is permitted as long as it is below a therapeutic level and administered at least 14 days prior to the first dose of study treatment.
Diagnosis of smoldering MM, Waldenström's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
Central nervous system involvement.
Diagnosed or treated for another malignancy within 2 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of any cause on clinical examination during the Screening period.
Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of study drug, including difficulty swallowing.
Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active hepatitis B or C infection.
Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study treatment.
Known allergy to any of the study medications, their analogues, or excipients in the various formulations.
Major surgery within 14 days before the first dose of study drug. (Note: kyphoplasty or vertebroplasty is not considered major surgery.)
Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
Treatment with any investigational products for reasons other than MM within 30 days before the first dose of study drug.

Name	Affiliation	Role
Medical Monitor	Millennium Pharmaceuticals, Inc.	Study Director

PubMed Identifier	Type	Citation	Retractions
30471652	Derived	Dimopoulos MA, Grosicki S, Jedrzejczak WW, Nahi H, Gruber A, Hansson M, Gupta N, Byrne C, Labotka R, Teng Z, Yang H, Grzasko N, Kumar S. All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. Eur J Cancer. 2019 Jan;106:89-98. doi: 10.1016/j.ejca.2018.09.011. Epub 2018 Nov 22.
30460684

ID	Title	Description
FG000	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.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Aug 22, 2016	Jun 24, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Combined Response Rate During the Induction Phase in Newly Diagnosed Multiple Myeloma (NDMM) Participants

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.

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.

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00033 OG00134

Title

Denominators

Categories

Title	Measurements
	OG00027(13 to 46) OG00124(11 to 41)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	P-value tests the null hypothesis: CR+VGPR rate=27% in treatment arms obtained using the one-sided Chi-Square test with alpha=0.10.	Chi-squared		0.4859														Other
OG001	P-value tests the null hypothesis: CR+VGPR rate=27% in treatment arms obtained using the one-sided Chi-Square test with alpha=0.10.

Primary

Overall Response Rate (ORR) in Relapsed and/or Refractory Multiple Myeloma (RRMM) Participants

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.

Posted

Mean

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	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.

Secondary

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

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.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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.

Secondary

Percentage of Participants With CR + VGPR + PR (ORR), CR, VGPR, PR and Stable Disease (SD), Progressive Disease (PD) During the Induction Phase

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.

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	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.

Secondary

Percentage of Participants With CR + VGPR + PR (ORR), CR + VGPR, CR, VGPR, PR, SD and PD Throughout the Entire Treatment Period in NDMM Participants

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	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.

Secondary

Time to Response (TTR) in NDMM Participants During the Induction Phase

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.

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.

Posted

Median

95% Confidence Interval

months

Up to 1 year

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Duration of Response (DOR) in NDMM Participants

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.

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.

Posted

Median

95% Confidence Interval

months

Up to 45 Months

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Time to Progression (TTP) in NDMM Participants

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

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.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Progression Free Survival (PFS) in NDMM Participants

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.

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.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	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.
OG001	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.

Secondary

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

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.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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.

Secondary

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

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).

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

Posted

Mean

Standard Deviation

score on a scale

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

ID	Title	Description
OG000	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.

Secondary

Percentage of Participants With CR + VGR + PR (ORR), CR, VGPR, and PR in NDMM Participants Remaining on Treatment After 13 Cycles

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.

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	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.

Secondary

Cmax: Maximum Observed Plasma Concentration for Ixazomib in NDMM Participants

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.

Posted

Mean

Standard Deviation

nanogram/mL (ng/mL)

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Tmax: Time to First Occurrence of Cmax for Ixazomib in NDMM Participants

Posted

Median

Full Range

hour (hr)

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in NDMM Participants

Posted

Mean

Standard Deviation

hr*ng/mL

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

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Number of Participants With AEs, Grade 3 or Higher AEs, AEs Resulting in Treatment Discontinuation, AEs Resulting in Dose Reduction, SAEs in RRMM Participants

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.

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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.

Units

Secondary

Cmax: Maximum Observed Plasma Concentration for Ixazomib in RRMM Participants

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Tmax: Time to First Occurrence of Cmax for Ixazomib in RRMM Participants

Posted

Median

Full Range

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

AUCtau: Area Under the Concentration-time Curve During a Dosing Interval for Ixazomib in RRMM Participants

Posted

Mean

Standard Deviation

hr*ng/mL

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

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With (CR + VGPR), CR, VGPR, PR, SD and PD in RRMM Participants

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	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.

Secondary

Time to Response (TTR) in RRMM Participants

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.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Duration of Response (DOR) in RRMM Participants

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.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Time to Progression (TTP) in RRMM Participants

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

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Progression Free Survival (PFS) in RRMM Participants

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.

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.

Posted

Median

95% Confidence Interval

months

Up to 45 months

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants

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

Posted

Mean

Standard Deviation

score on a scale

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

ID	Title	Description
OG000	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Pneumonia	Infections and infestations	MedDRA 20.0	Systematic Assessment	One treatment-emergent death occurred during treatment with Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) and is not related.	EG0004 affected36 at risk EG0012 affected34 at risk EG0023 affected78 at risk
Bronchitis	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0022 affected78 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0012 affected34 at risk EG0022 affected78 at risk
Sinusitis	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0021 affected78 at risk
Localised infection	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Diverticulitis	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Gastroenteritis	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Sepsis	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Septic shock	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Pseudomembranous colitis	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Escherichia sepsis	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Influenza	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Pseudomonal sepsis	Infections and infestations	MedDRA 20.0	Systematic Assessment	One treatment-emergent death occurred during treatment with Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM) and is related.	EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Pneumonia respiratory syncytial viral	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Cystitis	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0011 affected34 at risk EG0022 affected78 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0002 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Melaena	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	One treatment-emergent death occurred during treatment with Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) and is not related.	EG0001 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Rectal ulcer	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Ileus	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 20.0	Systematic Assessment		EG0003 affected36 at risk EG0011 affected34 at risk EG0021 affected78 at risk
Cardiac failure	Cardiac disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0012 affected34 at risk EG0021 affected78 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Angina pectoris	Cardiac disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Cardiac arrest	Cardiac disorders	MedDRA 20.0	Systematic Assessment	One treatment-emergent (TE) death occurred during treatment with Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM) and is not related.	EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0012 affected34 at risk EG0020 affected78 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment		EG0002 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0022 affected78 at risk
Plasma cell myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0022 affected78 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Benign bone neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Rectal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Myelodysplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Brain neoplasm benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	1 TE death occurred during treatment with Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM), 1 with Ixazomib 4.0 mg + CYC 400 mg/m^2 + DEX 40 mg (NDMM) and 1 with Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM) and all 3 are not related.	EG0001 affected36 at risk EG0011 affected34 at risk EG0021 affected78 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0012 affected34 at risk EG0020 affected78 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	One treatment-emergent death occurred during treatment with Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (NDMM) and is not related.	EG0001 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Pyrexia	General disorders	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0011 affected34 at risk EG0022 affected78 at risk
Fatigue	General disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 20.0	Systematic Assessment	One treatment-emergent death occurred during treatment with Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM) and is related.	EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 20.0	Systematic Assessment	One treatment-emergent death occurred during treatment with Ixazomib 4.0 mg + CYC 300 mg/m^2 + DEX 40 mg (RRMM) and is not related.	EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Syncope	Nervous system disorders	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Osteolysis	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0021 affected78 at risk
Tendon rupture	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0022 affected78 at risk
Renal failure	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Pemphigus	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment		EG0001 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Cataract	Eye disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Light chain analysis increased	Investigations	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Hypotension	Vascular disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment		EG0000 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0009 affected36 at risk EG0013 affected34 at risk EG00221 affected78 at risk
Bronchitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0005 affected36 at risk EG0014 affected34 at risk EG00212 affected78 at risk
Nasopharyngitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0005 affected36 at risk EG0014 affected34 at risk EG0026 affected78 at risk
Respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 affected36 at risk EG0014 affected34 at risk EG0028 affected78 at risk
Herpes zoster	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0006 affected36 at risk EG0013 affected34 at risk EG0025 affected78 at risk
Influenza	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 affected36 at risk EG0010 affected34 at risk EG0026 affected78 at risk
Conjunctivitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0011 affected34 at risk EG0025 affected78 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0013 affected34 at risk EG0023 affected78 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0010 affected34 at risk EG0025 affected78 at risk
Pharyngitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0011 affected34 at risk EG0023 affected78 at risk
Pneumonia	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0011 affected34 at risk EG0024 affected78 at risk
Oral herpes	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0010 affected34 at risk EG0023 affected78 at risk
Cellulitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Gastroenteritis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0012 affected34 at risk EG0021 affected78 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0012 affected34 at risk EG0020 affected78 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG00011 affected36 at risk EG0019 affected34 at risk EG00226 affected78 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0008 affected36 at risk EG00110 affected34 at risk EG00219 affected78 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0006 affected36 at risk EG0019 affected34 at risk EG0029 affected78 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0008 affected36 at risk EG0017 affected34 at risk EG0028 affected78 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0013 affected34 at risk EG0026 affected78 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0012 affected34 at risk EG0024 affected78 at risk
Flatulence	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0010 affected34 at risk EG0024 affected78 at risk
Gastritis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0011 affected34 at risk EG0021 affected78 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG00011 affected36 at risk EG00111 affected34 at risk EG00219 affected78 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0006 affected36 at risk EG00116 affected34 at risk EG00215 affected78 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected36 at risk EG0014 affected34 at risk EG00218 affected78 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0011 affected34 at risk EG0024 affected78 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0011 affected34 at risk EG0024 affected78 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0011 affected34 at risk EG0021 affected78 at risk
Fatigue	General disorders	MedDRA 20.0	Systematic Assessment	EG0008 affected36 at risk EG0017 affected34 at risk EG00215 affected78 at risk
Oedema peripheral	General disorders	MedDRA 20.0	Systematic Assessment	EG0008 affected36 at risk EG0019 affected34 at risk EG0025 affected78 at risk
Pyrexia	General disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected36 at risk EG0016 affected34 at risk EG0024 affected78 at risk
Influenza like illness	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0011 affected34 at risk EG0024 affected78 at risk
Non-cardiac chest pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0011 affected34 at risk EG0024 affected78 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0006 affected36 at risk EG00110 affected34 at risk EG00210 affected78 at risk
Dizziness	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected36 at risk EG0012 affected34 at risk EG0027 affected78 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected36 at risk EG0013 affected34 at risk EG0025 affected78 at risk
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected36 at risk EG0013 affected34 at risk EG0023 affected78 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected36 at risk EG0011 affected34 at risk EG0023 affected78 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected36 at risk EG0016 affected34 at risk EG0026 affected78 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected36 at risk EG0015 affected34 at risk EG0027 affected78 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0005 affected36 at risk EG0014 affected34 at risk EG0022 affected78 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected36 at risk EG0010 affected34 at risk EG0026 affected78 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0011 affected34 at risk EG0024 affected78 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0011 affected34 at risk EG0024 affected78 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0011 affected34 at risk EG0020 affected78 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0012 affected34 at risk EG0023 affected78 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0004 affected36 at risk EG0010 affected34 at risk EG0023 affected78 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0011 affected34 at risk EG0023 affected78 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0012 affected34 at risk EG0023 affected78 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0013 affected34 at risk EG0021 affected78 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0010 affected34 at risk EG0021 affected78 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0012 affected34 at risk EG0021 affected78 at risk
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0010 affected34 at risk EG0020 affected78 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0003 affected36 at risk EG0014 affected34 at risk EG0027 affected78 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0010 affected34 at risk EG0026 affected78 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0014 affected34 at risk EG0022 affected78 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0013 affected34 at risk EG0023 affected78 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0011 affected34 at risk EG0024 affected78 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0011 affected34 at risk EG0021 affected78 at risk
Insomnia	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0013 affected34 at risk EG00210 affected78 at risk
Anxiety	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0012 affected34 at risk EG0020 affected78 at risk
Confusional state	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0012 affected34 at risk EG0021 affected78 at risk
Hypertension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0002 affected36 at risk EG0017 affected34 at risk EG0022 affected78 at risk
Hypotension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0012 affected34 at risk EG0022 affected78 at risk
Weight decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0004 affected36 at risk EG0013 affected34 at risk EG0021 affected78 at risk
Blood creatinine increased	Investigations	MedDRA 20.0	Systematic Assessment	EG0003 affected36 at risk EG0012 affected34 at risk EG0020 affected78 at risk
Cataract	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0012 affected34 at risk EG0025 affected78 at risk
Glaucoma	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0000 affected36 at risk EG0012 affected34 at risk EG0020 affected78 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0012 affected34 at risk EG0022 affected78 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0012 affected34 at risk EG0021 affected78 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0013 affected34 at risk EG0023 affected78 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 affected36 at risk EG0013 affected34 at risk EG0021 affected78 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Hazard	Kentucky		United States

ID	Term
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D006474	Hemorrhagic Disorders
D008232	Lymphoproliferative Disorders
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	3	36	17	36	34	36
EG001	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.	2	34	20	34	34	34
EG002	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.	5	78	30	78	69	78