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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-023772-71 | EudraCT Number |
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The purpose of this phase 1/2, open-label study was to evaluate the effect of oral formulation of Ixazomib when added to standard melphalan and prednisone (MP) treatment. Both phases of the study included participants who had newly diagnosed multiple myeloma and were ineligible for high-dose therapy plus stem cell transplantation because of age (≥65 years of age) or coexisting conditions and for whom standard MP treatment was indicated.
The drug tested in this study was called ixazomib (MLN9708). Ixazomib was tested to treat the people with newly diagnosed multiple myeloma requiring systemic treatment who were not eligible for stem cell transplantation. This study determined the safety, tolerability, efficacy, quality of life (QOL), and pharmacokinetics (PK)/pharmacodynamics (PD) of ixazomib.
The study enrolled 61 patients. The study was conducted in 2 parts: 1) phase 1 dose escalation and 2) phase 2 expansion at maximum tolerated dose. Participants were enrolled to receive:
This multicenter trial was conducted in the Unites states, Canada, United Kingdom, Spain and Czech Republic. The overall time to participate in this study is 5.5 years. Participants made multiple visits to the clinic and were followed up every 16 weeks after end of treatment until disease progression if stopped treatment before disease progression and then every 16 weeks up to start of next therapy or death whichever occurs first.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Ixazomib 3.0 mg | Experimental | Ixazomib 3.0 mg, capsules, orally, on Days 1, 4, 8, 11, 22, 25, 29, 32 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle for up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 23 maintenance cycles; overall up to 32 cycles [34 months]). |
|
| Arm A: Ixazomib 3.7 mg | Experimental | Ixazomib 3.7 mg, capsules, orally, on Days 1, 4, 8, 11, 22, 25, 29, 32 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 10 maintenance cycles; overall up to 19 cycles [21 months]). |
|
| Arm B: Ixazomib 3.0 mg | Experimental | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ixazomib | Drug | Ixazomib capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Ixazomib (Phase 1) | The RP2D is the maximum tolerated dose (MTD) or less. The MTD is defined as the dose range at which ≤ 1 of 6 evaluable participants experience dose limiting toxicities (DLT) within the first 28 days of treatment (end of Cycle 1). | Cycle 1, phase 1 (Up to 42 days) |
| Very Good Partial Response (VGPR) or Better Response Rate (Phase 2) | VGPR or better response rate is defined as percentage of participants with a complete response (CR) and very good partial response (VGPR). Per International Myeloma Working Group Uniform Response Criteria (IMWG), CR: 1) Negative immunofixation on the serum and urine, 2) Disappearance of any soft tissue plasmacytomas and 3) < 5% plasma cells in bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hour. | Day 1 of every other cycle from Day 1 of Cycle 2 (each cycle of 28 days) until death (Up to 5.5 years) |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Inhibition Rate (Emax) (Phase 1) | Whole blood 20S proteasome inhibition parameters | At multiple time points during Cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 days depending on the arm of the study |
| Time of Occurrence of Emax (TEmax) (Phase 1) |
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Inclusion Criteria:
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lebanon | New Hampshire | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29954932 | Derived | San-Miguel JF, Echeveste Gutierrez MA, Spicka I, Mateos MV, Song K, Craig MD, Blade J, Hajek R, Chen C, Di Bacco A, Estevam J, Gupta N, Byrne C, Lu V, van de Velde H, Lonial S. A phase I/II dose-escalation study investigating all-oral ixazomib-melphalan-prednisone induction followed by single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma. Haematologica. 2018 Sep;103(9):1518-1526. doi: 10.3324/haematol.2017.185991. Epub 2018 Jun 28. |
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Participants with a diagnosis of multiple myeloma (previously untreated) were enrolled to receive ixazomib orally at various doses in Phase 1. Only Arm B: Ixazomib 4.0 mg continued in Phase 2.
Participants took part in the study at 14 investigative sites in United States Canada, United Kingdom, Spain, and Czech Republic from 27 June 2011 to 29 December 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 4, 8, 11, 22, 25, 29, 32 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle for up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 23 maintenance cycles; overall up to 32 cycles [34 months]). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Arm B: Ixazomib 4.0 mg | Experimental | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
|
| Arm B: Ixazomib 5.5 mg | Experimental | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
|
| Arm C: Ixazomib 3.0 mg | Experimental | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
|
| Arm C: Ixazomib 4.0 mg | Experimental | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
|
| Arm D: Ixazomib 4.0 mg | Experimental | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
|
| Melphalan | Drug | Melphalan tablets |
|
| Prednisone | Drug | Prednisone tablets |
|
Whole blood 20S proteasome inhibition parameters |
| At multiple time points during Cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 days depending on the arm of the study |
| Cmax: Maximum Observed Plasma Concentration for Ixazomib (Phase 1) | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib (Phase 1) | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
| AUCtau: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Ixazomib (Phase 1) | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
| Terminal Elimination Rate Constant (λz) for Ixazomib (Phase 1) | Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase. | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
| Terminal Phase Elimination Half-life (T1/2) for Ixazomib (Phase 1) | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
| Observed Accumulation Ratio for AUCtau (Rac) (Phase 1) | Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 14 divided by area under the curve from time zero to end of dosing interval (AUCtau) on Day 1. | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
| Overall Response Rate (ORR) | ORR is defined as percentage of participants with overall response including CR, VGPR, and partial response (PR). Per IMWG criteria, CR:1)Negative immunofixation on serum and urine, 2)Disappearance of any soft tissue plasmacytomas, 3)< 5% plasma cells in bone marrow. VGPR: Serum+urine M-protein detectable by immunofixation but not on electrophoresis/ 90% or >reduction in serum M-protein + urine M-protein level < 100 mg/ 24-hour. PR:1)≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24-hour. If serum+urine M-protein are unmeasurable, ≥50% decrease in difference between involved and uninvolved FLC levels is required. If serum+urine M-protein are unmeasurable and serum free light assay is also unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition, if present at baseline, a ≥50% reduction in size of soft tissue plasmacytomas is required. | Day 1 of every other cycle from Day 1 of Cycle 2 (each cycle of 28 days) up to 61 cycles, at end of treatment (Up to 5.5 years) |
| Time to First Response (Phase 2) | Response is defined as CR, VGPR and PR. Per IMWG criteria, CR:1)Negative immunofixation on serum+urine, 2)Disappearance of any soft tissue plasmacytomas, 3)< 5% plasma cells in bone marrow. VGPR: Serum+urine M-protein detectable by immunofixation but not on electrophoresis/ 90% or >reduction in serum M-protein + urine M-protein level < 100 mg/ 24-hour. PR:1)≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24-hour. If serum+urine M-protein are unmeasurable, ≥50% decrease in difference between involved and uninvolved FLC levels is required. Else, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition, if present at baseline, a ≥50% reduction in size of soft tissue plasmacytomas is required. | From the date of enrollment to the date of the first documented response for up to 5.5 years |
| Duration of Response (DOR) (Phase 2) | DOR is defined as time of first documentation of a confirmed PR or better response to first documented PD or start of alternative therapy. DOR was presented for those achieving CR+VGPR+PR. Per IMWG criteria, CR:1)Negative immunofixation on serum+urine, 2)Disappearance of any soft tissue plasmacytomas, 3)< 5% plasma cells in bone marrow. VGPR: Serum+urine M-protein detectable by immunofixation but not on electrophoresis/ 90% or >reduction in serum M-protein + urine M-protein level < 100 mg/ 24-hour. PR:1)≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24-hour. If serum+urine M-protein are unmeasurable, ≥50% decrease in difference between involved and uninvolved FLC levels is required. Else, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition, if present at baseline, a ≥50% reduction in size of soft tissue plasmacytomas is required. | From the time from the date of first documentation of PR or better to the date of first documented disease progression for up to 5.5 years |
| Time to Progression (TTP) (Phase 2) | TTP is defined as time from date of enrollment to date of first documented disease progression (PD). Per IMWG criteria, progressive disease requires any 1 or more of following: Increase of ≥25% from nadir in serum M-component and/or (absolute increase must be ≥0.5 g/dL), urine M-component and/or (absolute increase must be ≥200 mg/24 hour. Participants without measurable serum+urine M-protein levels: difference between involved and uninvolved FLC levels. The absolute increase must be >10 mg/dL. Bone marrow plasma cell percentage: absolute % must be ≥10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.85 mmol/L) that can be attributed solely to plasma cell proliferative disorder. | From the date of enrollment to the date of the first documented disease progression for up to 5.5 years |
| Time to Next Therapy (Phase 2) | Time to Next Therapy is defined as time from the date of enrollment to the date of subsequent antineoplastic therapy. | From the date of enrollment to the date of subsequent antineoplastic therapy for up to 5.5 years |
| Progression Free Survival (Phase 2) | Progression Free Survival is defined as time in months from start of study treatment to first documentation of objective tumor progression per investigator assessment or up to death due to any cause, whichever occurs first. Per IMWG criteria, progressive disease requires any 1 or more of following: Increase of ≥25% from nadir in serum M-component and/or (absolute increase must be ≥0.5 g/dL), urine M-component and/or (absolute increase must be ≥200 mg/24 hour. Participants without measurable serum+urine M-protein levels: difference between involved and uninvolved FLC levels. The absolute increase must be >10 mg/dL. Bone marrow plasma cell percentage: absolute % must be ≥10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.85 mmol/L) that can be attributed solely to plasma cell proliferative disorder. | From the date of enrollment to the date of the first documented disease progression or death due to any cause for up to 5.5 years |
| Overall Survival (Phase 2) | Overall Survival is the time in months from start of study treatment to date of death due to any cause. | From date of enrollment to date of death, approximately 5.5 years (Approximate median follow-up: 43.6 months) |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. | From first dose of study drug through 30 days after last dose of study drug or until the start of subsequent antineoplastic therapy for up to 5.6 years |
| Assessments of Quality of Life (Phase 2) | Baseline, Day 1 of each treatment cycle, and Day 1 of each maintenance cycle, up to 5.5 years |
| Morgantown |
| West Virginia |
| United States |
| Vancouver | British Columbia | Canada |
| Toronto | Ontario | Canada |
| Québec | Canada |
| Brno | Czechia |
| Prague | Czechia |
| Badalona | Spain |
| Barcelona | Spain |
| Donostia / San Sebastian | Spain |
| Madrid | Spain |
| Salamanca | Spain |
| Seville | Spain |
| Bournemouth | United Kingdom |
| Brighton | United Kingdom |
| Cambridge | United Kingdom |
| London | United Kingdom |
| Nottingham | United Kingdom |
| Oxford | United Kingdom |
| Uxbridge | United Kingdom |
| FG001 | Arm A: Ixazomib 3.7 mg | Ixazomib 3.7 mg, capsules, orally, on Days 1, 4, 8, 11, 22, 25, 29, 32 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 10 maintenance cycles; overall up to 19 cycles [21 months]). |
| FG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| FG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
| FG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
| FG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
| FG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
| FG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
| COMPLETED |
|
| NOT COMPLETED |
|
|
The safety population consisted of participants who received at least 1 dose of any study drug.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: Ixazomib 3.0 - 3.7 mg | Ixazomib 3.0 - 3.7 mg, capsules, orally, on Days 1, 4, 8, 11, 22, 25, 29, 32 plus melphalan 9 mg/m^2, tablets, orally, on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 23 maintenance cycles; overall up to 32 cycles). |
| BG001 | Arm B: Ixazomib 3.0 - 5.5 mg | Ixazomib 3.0 - 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally, on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1-4 for in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles). |
| BG002 | Arm C: Ixazomib 3.0 - 4.0 mg | Ixazomib 3.0 - 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally, on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles). |
| BG003 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles). |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||
| Age, Customized | Count of Participants | Participants |
| |||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| |||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| |||||||||||
| Region of Enrollment | Count of Participants | Participants |
| |||||||||||
| Height | Height data was only available for 11, 33, 9 and 6 participants in the Arms A, B, C and D respectively. | Mean | Standard Deviation | cm |
| |||||||||
| Weight at Baseline | Mean | Standard Deviation | kg |
| ||||||||||
| Body Surface Area at Baseline | Body Surface Area (m^2) = square root [height (cm) x weight (kg) / 3600]. | Body Surface Area data was only available for 11, 33, 9 and 6 participants in the Arms A, B, C and D respectively. | Mean | Standard Deviation | m^2 |
|
| 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 | Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Ixazomib (Phase 1) | The RP2D is the maximum tolerated dose (MTD) or less. The MTD is defined as the dose range at which ≤ 1 of 6 evaluable participants experience dose limiting toxicities (DLT) within the first 28 days of treatment (end of Cycle 1). | Dose Limiting Toxicity population included participants who received at least 80% of doses of MLN9708 and melphalan during Cycle 1 in Arms A or all doses of MLN9708 and melphalan during Cycle 1 in Arm B, C, D, or experience a DLT in Cycle 1 in the phase 1 dose escalation portion. | Posted | Number | mg | Cycle 1, phase 1 (Up to 42 days) |
|
|
| |||||||||||||||||||||||||||||||||||
| Primary | Very Good Partial Response (VGPR) or Better Response Rate (Phase 2) | VGPR or better response rate is defined as percentage of participants with a complete response (CR) and very good partial response (VGPR). Per International Myeloma Working Group Uniform Response Criteria (IMWG), CR: 1) Negative immunofixation on the serum and urine, 2) Disappearance of any soft tissue plasmacytomas and 3) < 5% plasma cells in bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hour. | The response-evaluable population is defined as participants who received at least 5 of 8 MLN9708 doses in Arm A, at least 2 of 3 MLN9708 doses in Arm B, at least 4 of 5 MLN9708 doses in Arm C, or at least 3 of 4 MLN9708 doses in Arm D and had measurable disease at baseline and at least 1 post-baseline response assessment. | Posted | Number | percentage of participants | Day 1 of every other cycle from Day 1 of Cycle 2 (each cycle of 28 days) until death (Up to 5.5 years) |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Maximum Inhibition Rate (Emax) (Phase 1) | Whole blood 20S proteasome inhibition parameters | Due to the change in the planned analysis, the efficacy endpoint of maximum inhibition rate was not performed. | Posted | At multiple time points during Cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 days depending on the arm of the study |
| |||||||||||||||||||||||||||||||||||||||
| Secondary | Time of Occurrence of Emax (TEmax) (Phase 1) | Whole blood 20S proteasome inhibition parameters | The efficacy endpoint of maximum inhibition rate was not performed due to the change in the planned analysis. | Posted | At multiple time points during Cycles 1-3 of each phase and arm of the study, throughout approximately 84-126 days depending on the arm of the study |
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| Secondary | Cmax: Maximum Observed Plasma Concentration for Ixazomib (Phase 1) | The pharmacokinetics (PK) population consisted of all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
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| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib (Phase 1) | The PK population consisted of all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. | Posted | Median | Full Range | hours | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
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| Secondary | AUCtau: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Ixazomib (Phase 1) | The PK population consisted of all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. | Posted | Mean | Standard Deviation | hr*ng/mL | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
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| Secondary | Terminal Elimination Rate Constant (λz) for Ixazomib (Phase 1) | Terminal elimination rate constant, calculated as the negative of the slope of the log-linear regression of the natural logarithm concentration-time curve during the terminal phase. | The PK population consisted of all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. | Posted | Mean | Standard Deviation | 1/hour | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
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| Secondary | Terminal Phase Elimination Half-life (T1/2) for Ixazomib (Phase 1) | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. | The PK population consisted of all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. | Posted | Mean | Standard Deviation | hours | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
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| Secondary | Observed Accumulation Ratio for AUCtau (Rac) (Phase 1) | Accumulation ratio for AUCtau (Rac) was calculated as area under the curve from time zero to end of dosing interval (AUCtau) on Day 14 divided by area under the curve from time zero to end of dosing interval (AUCtau) on Day 1. | The PK population consisted of all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. | Posted | Mean | Standard Deviation | ratio | Pre-dose on Day 1 and at multiple timepoints (up to 8 hours) on Day 11 for Arm A, Day 15 for Arm B and Day 29 for Arms C and D |
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| Secondary | Overall Response Rate (ORR) | ORR is defined as percentage of participants with overall response including CR, VGPR, and partial response (PR). Per IMWG criteria, CR:1)Negative immunofixation on serum and urine, 2)Disappearance of any soft tissue plasmacytomas, 3)< 5% plasma cells in bone marrow. VGPR: Serum+urine M-protein detectable by immunofixation but not on electrophoresis/ 90% or >reduction in serum M-protein + urine M-protein level < 100 mg/ 24-hour. PR:1)≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24-hour. If serum+urine M-protein are unmeasurable, ≥50% decrease in difference between involved and uninvolved FLC levels is required. If serum+urine M-protein are unmeasurable and serum free light assay is also unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition, if present at baseline, a ≥50% reduction in size of soft tissue plasmacytomas is required. | The response-evaluable population is defined as participants who received at least 5 of 8 MLN9708 doses in Arm A, at least 2 of 3 MLN9708 doses in Arm B, at least 4 of 5 MLN9708 doses in Arm C, or at least 3 of 4 MLN9708 doses in Arm D and had measurable disease at baseline and at least 1 post-baseline response assessment. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 1 of every other cycle from Day 1 of Cycle 2 (each cycle of 28 days) up to 61 cycles, at end of treatment (Up to 5.5 years) |
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| Secondary | Time to First Response (Phase 2) | Response is defined as CR, VGPR and PR. Per IMWG criteria, CR:1)Negative immunofixation on serum+urine, 2)Disappearance of any soft tissue plasmacytomas, 3)< 5% plasma cells in bone marrow. VGPR: Serum+urine M-protein detectable by immunofixation but not on electrophoresis/ 90% or >reduction in serum M-protein + urine M-protein level < 100 mg/ 24-hour. PR:1)≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24-hour. If serum+urine M-protein are unmeasurable, ≥50% decrease in difference between involved and uninvolved FLC levels is required. Else, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition, if present at baseline, a ≥50% reduction in size of soft tissue plasmacytomas is required. | The safety population consisted of participants who received at least 1 dose of any study drug. | Posted | Median | 95% Confidence Interval | months | From the date of enrollment to the date of the first documented response for up to 5.5 years |
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| Secondary | Duration of Response (DOR) (Phase 2) | DOR is defined as time of first documentation of a confirmed PR or better response to first documented PD or start of alternative therapy. DOR was presented for those achieving CR+VGPR+PR. Per IMWG criteria, CR:1)Negative immunofixation on serum+urine, 2)Disappearance of any soft tissue plasmacytomas, 3)< 5% plasma cells in bone marrow. VGPR: Serum+urine M-protein detectable by immunofixation but not on electrophoresis/ 90% or >reduction in serum M-protein + urine M-protein level < 100 mg/ 24-hour. PR:1)≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24-hour. If serum+urine M-protein are unmeasurable, ≥50% decrease in difference between involved and uninvolved FLC levels is required. Else, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition, if present at baseline, a ≥50% reduction in size of soft tissue plasmacytomas is required. | The safety population consisted of participants who received at least 1 dose of any study drug. | Posted | Median | 95% Confidence Interval | months | From the time from the date of first documentation of PR or better to the date of first documented disease progression for up to 5.5 years |
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| Secondary | Time to Progression (TTP) (Phase 2) | TTP is defined as time from date of enrollment to date of first documented disease progression (PD). Per IMWG criteria, progressive disease requires any 1 or more of following: Increase of ≥25% from nadir in serum M-component and/or (absolute increase must be ≥0.5 g/dL), urine M-component and/or (absolute increase must be ≥200 mg/24 hour. Participants without measurable serum+urine M-protein levels: difference between involved and uninvolved FLC levels. The absolute increase must be >10 mg/dL. Bone marrow plasma cell percentage: absolute % must be ≥10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.85 mmol/L) that can be attributed solely to plasma cell proliferative disorder. | The safety population consisted of participants who received at least 1 dose of any study drug. | Posted | Median | 95% Confidence Interval | months | From the date of enrollment to the date of the first documented disease progression for up to 5.5 years |
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| Secondary | Time to Next Therapy (Phase 2) | Time to Next Therapy is defined as time from the date of enrollment to the date of subsequent antineoplastic therapy. | Time to next therapy was not analyzed due to the change in the planned analysis. | Posted | From the date of enrollment to the date of subsequent antineoplastic therapy for up to 5.5 years |
|
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| Secondary | Progression Free Survival (Phase 2) | Progression Free Survival is defined as time in months from start of study treatment to first documentation of objective tumor progression per investigator assessment or up to death due to any cause, whichever occurs first. Per IMWG criteria, progressive disease requires any 1 or more of following: Increase of ≥25% from nadir in serum M-component and/or (absolute increase must be ≥0.5 g/dL), urine M-component and/or (absolute increase must be ≥200 mg/24 hour. Participants without measurable serum+urine M-protein levels: difference between involved and uninvolved FLC levels. The absolute increase must be >10 mg/dL. Bone marrow plasma cell percentage: absolute % must be ≥10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.85 mmol/L) that can be attributed solely to plasma cell proliferative disorder. | The safety population consisted of participants who received at least 1 dose of any study drug. | Posted | Median | 95% Confidence Interval | months | From the date of enrollment to the date of the first documented disease progression or death due to any cause for up to 5.5 years |
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| Secondary | Overall Survival (Phase 2) | Overall Survival is the time in months from start of study treatment to date of death due to any cause. | The safety population consisted of participants who received at least 1 dose of any study drug. | Posted | Median | 95% Confidence Interval | months | From date of enrollment to date of death, approximately 5.5 years (Approximate median follow-up: 43.6 months) |
|
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. | The safety population consisted of participants who received at least 1 dose of any study drug. | Posted | Number | participants | From first dose of study drug through 30 days after last dose of study drug or until the start of subsequent antineoplastic therapy for up to 5.6 years |
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| Secondary | Assessments of Quality of Life (Phase 2) | Assessments of quality of life parameters were not analyzed due to change in planned analysis. | Posted | Baseline, Day 1 of each treatment cycle, and Day 1 of each maintenance cycle, up to 5.5 years |
|
|
From first dose of study drug through 30 days after last dose of study drug or until the start of subsequent antineoplastic therapy for up to 5.6 years
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 4, 8, 11, 22, 25, 29, 32 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle for up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 23 maintenance cycles; overall up to 32 cycles [34 months]). | 2 | 7 | 7 | 7 | ||
| EG001 | Arm A: Ixazomib 3.7 mg | Ixazomib 3.7 mg, capsules, orally, on Days 1, 4, 8, 11, 22, 25, 29, 32 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 10 maintenance cycles; overall up to 19 cycles [21 months]). | 4 | 4 | 4 | 4 | ||
| EG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). | 3 | 3 | 3 | 3 | ||
| EG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). | 12 | 26 | 26 | 26 | ||
| EG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). | 3 | 5 | 5 | 5 | ||
| EG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). | 4 | 6 | 6 | 6 | ||
| EG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). | 2 | 4 | 4 | 4 | ||
| EG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). | 1 | 6 | 6 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 19.0 | Systematic Assessment | One treatment-emergent death occurred in Arm B during treatment with ixazombib 4.0 mg and is not related. |
|
| Bronchitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 19.0 | Systematic Assessment | One treatment-emergent death occurred in Arm B during treatment with ixazombib 4.0 mg and is not related. |
|
| Ileus | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Subileus | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oesophageal ulcer haemorrhage | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Chest injury | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Face injury | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Polyneuropathy | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Cachexia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Supraventricular tachycardia | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neurogenic bladder | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Plasma cell myeloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment | One treatment-emergent death occurred in Arm B during treatment with ixazombib 4.0 mg and is not related. |
|
| Depression | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Generalised erythema | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Tongue ulceration | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Abdominal hernia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Gastric disorder | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Gastrointestinal motility disorder | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Tongue eruption | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Feeling cold | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Inflammation | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Chronic fatigue syndrome | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Feeling hot | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Polyarthritis | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Muscle swelling | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Cushingoid | Endocrine disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Uterine haemorrhage | Reproductive system and breast disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
| |
| Plasmacytoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Atrial flutter | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Atrial tachycardia | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Supraventricular extrasystoles | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Blepharitis | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Eyelid oedema | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Erythema of eyelid | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Eye pruritus | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Eye swelling | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Ulcerative keratitis | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Visual acuity reduced | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Vitreous floaters | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Compression fracture | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Face injury | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Injury | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Synovial rupture | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Anuria | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Disorientation | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Blood electrolytes decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Body temperature increased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Influenza A virus test positive | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Liver function test increased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Peripheral venous disease | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Peripheral coldness | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Catarrh | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Acute pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pharyngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Electrolyte imbalance | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Ataxia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Ageusia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Autonomic nervous system imbalance | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Burning sensation | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dementia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dementia Alzheimer's type | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dizziness postural | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dysaesthesia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Polyneuropathy | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Klebsiella infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Oesophageal candidiasis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Streptococcal infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Urethritis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Vulvovaginal candidiasis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Erythema nodosum | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Generalised erythema | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| 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 |
Not provided
Not provided
| ID | Term |
|---|---|
| C548400 | ixazomib |
| D008558 | Melphalan |
| D011241 | Prednisone |
| ID | Term |
|---|---|
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
|
|
| >=75 |
|
|
|
|
| Not Hispanic or Latino |
|
|
|
| Black or African American |
|
|
| White |
|
|
| Other |
|
|
|
| Czech Republic |
|
|
| Spain |
|
|
| United Kingdom |
|
|
| United States |
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| OG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
| OG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
| OG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
| OG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
| OG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
|
| OG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| OG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
| OG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
| OG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
| OG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
| OG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
|
| OG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| OG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
| OG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
| OG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
| OG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
| OG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
|
|
| OG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| OG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
| OG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
| OG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
| OG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
| OG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
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| OG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| OG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
| OG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
| OG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
| OG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
| OG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
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| OG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| OG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
| OG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
| OG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
| OG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
| OG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
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| OG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| OG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
| OG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
| OG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
| OG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
| OG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
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| OG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| OG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
| OG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
| OG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
| OG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
| OG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
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| OG001 | Arm A: Ixazomib 3.7 mg | Ixazomib 3.7 mg, capsules, orally, on Days 1, 4, 8, 11, 22, 25, 29, 32 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 10 maintenance cycles; overall up to 19 cycles [21 months]). |
| OG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| OG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
| OG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
| OG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
| OG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
| OG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
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| OG002 | Arm B: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles [25 months]). |
| OG003 | Arm B: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles [58 months]). |
| OG004 | Arm B: Ixazomib 5.5 mg | Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles [24 months]). |
| OG005 | Arm C: Ixazomib 3.0 mg | Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles [40 months]). |
| OG006 | Arm C: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles [24 months]). |
| OG007 | Arm D: Ixazomib 4.0 mg | Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles [38 months]). |
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