A Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT)
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the effect of ixazomib maintenance therapy on progression free survival (PFS) compared with placebo, in participants with NDMM who have had a major response (complete response [CR], very good partial response [VGPR], or partial response [PR]) to initial therapy and who have not undergone SCT.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The drug being tested in this study is called ixazomib citrate. Ixazomib citrate is being tested to slow progressive disease (PD) and improve overall survival in people who have NDMM who have had a major positive response to initial therapy and have not undergone SCT. This study will look at the effect of ixazomib citrate has on the length of time that participants are free of PD and their overall survival.
The study will enrol approximately 700 participants. Participants will be randomly assigned (by chance, like flipping a coin) in 3:2 ratio to Ixazomib or matching placebo groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
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Ixazomib citrate initiates at 3 mg which will be escalated to 4 mg with cycle 5 day 1
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Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has no active ingredient
All participants will be asked to take one capsule on Days 1, 8 and 15 of each 28-day cycle. The treatment period will be approximately 24 months (equivalent to 26 cycles) or until patients experience PD or unacceptable toxicities, whichever occurs first.
This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 78 to 106 months. Participants will make 28 visits to the clinic during the treatment period and will continue to make follow-up visits every 4 weeks until the next line of therapy begins. Participants will also be contacted by telephone every 12 weeks after last treatment visit for a follow-up assessment.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Ixazomib placebo-matching capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib placebo-matching capsules, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019). |
Drug: Placebo
Ixazomib placebo-matching capsules.
|
| Experimental: Ixazomib Ixazomib 3 mg, capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib 3 or 4 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019). |
Drug: Ixazomib
Ixazomib capsules.
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) [From the randomization until progressive disease (PD) or death or data cut-off date (12 Aug 2019) (Up to approximately 42 months)]
PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first. Per IMWG criteria, PD definition: increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/dl); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved FLC levels (absolute increase >10 mg/dl); or bone marrow plasma cell percentage (absolute plasma cell percentage ≥10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia (corrected serum calcium >11.5mg/dl).
Secondary Outcome Measures
- Overall Survival (OS) [From the date of randomization every 12 weeks after PD on next-line therapy until death (Up to approximately 76 to 104 months)]
OS will be measured as the time from the date of randomization to the date of death.
- Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period [Up to 24 months]
Response will be assessed according to IMWG criteria. Best response includes PR, VGPR and CR.
- Time to Progression (TTP) [From the date of randomization to the date of first documented PD (Up to approximately 76 to 104 months)]
TTP is defined as the time from the date of randomization to the date of first documentation of PD, using IMWG criteria.
- Progression Free Survival 2 (PFS2) [From the date of randomization to every 12 weeks until 2nd PD or death (Up to approximately 76 to 104 months)]
PFS2 is defined as the time from the date of randomization to objective PD on next-line treatment using IMWG criteria, or death due to any cause, whichever occurs first.
- Time to Next Line Therapy (TTNT) [From the date of randomization to the date of the first dose of the next-line of therapy (Up to approximately 76 to 104 months)]
TTNT is defined as the time from the date of randomization to the date of the first dose of next-line antineoplastic therapy.
- Time to End of the Next-line of Therapy After Study Treatment [From the date of randomization to the date of last dose of the next-line of therapy (Up to approximately 76 to 104 months)]
Time to end of the next line of therapy is defined as the time from the date of randomization to the date of last dose of the next line of antineoplastic therapy following study treatment.
- Duration of Next-line Therapy [From the date of the first dose of the line of antineoplastic therapy coming after study treatment to the date of the last dose (Up to approximately 76 to 104 months)]
Duration of next-line therapy is defined as the time from the date of the first dose of the line of antineoplastic therapy coming after study treatment to the date of the last dose.
- Percentage of Participants Who Develop A New Primary Malignancy [From the randomization date till death or termination of the study (Up to approximately 76 to 104 months)]
- Percentage of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative, or the Maintenance of MRD Negativity [Screening, Cycle 13, and Cycle 26 (Cycle length is equal to [=] 28 days)]
Bone marrow aspirates and blood samples will be sent to a central laboratory and will be assessed for MRD using flow cytometry. MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD.
- Correlation of MRD Status With PFS and OS [Screening, Cycle 13, and Cycle 26 (Cycle length=28 days)]
PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurs first. OS will be measured as the time from the date of randomization to the date of death.
- OS in a High-risk Population [From the date of randomization to every 12 weeks after PD on next-line therapy until death (Up to approximately 76 to 104 months)]
High-risk population will include but not be limited to participants carrying deletion (del)17, t(4;14), t(14;16). OS will be measured as the time from the date of randomization to the date of death.
- PFS in a High-risk Population [From the date of randomization to every 4 weeks during follow-up until PD or death (Up to approximately 76 to 104 months)]
High-risk population will include but not be limited to participants carrying del17, t(4;14), t(14;16). PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause.
- Eastern Cooperative Oncology Group (ECOG) Performance Status [Cycle 2 and every 28 days ( Up to 24 months) (Cycle length =28 days)]
ECOG performance status assess participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory ( greater than [>] 50 percent [%] of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead.
- Percentage of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) [First dose of study drug through 30 days after last dose of study drug (Up to 25 months)]
AEs are defined as any unfavourable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug. A SAE means any untoward medical occurrence that results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is considered medically significant.
- Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [Baseline and every 28 days (Up to 24 months)]
The EORTC QLQ-C30 is completed by the participant. The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best).
- Number of Participants With Any Markedly Abnormal Standard Safety Laboratory Values [From First dose date of study drug through 30 days after the last dose of study drug (Up to 25 months)]
Clinical laboratory evaluations will be performed by a central laboratory. The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.
- Correlation Between Frailty Status and PFS and OS [Up to approximately 76 to 104 months]
Participant's frailty status is classified as fit, unfit or frail on the bases of 4 components: age, the Charlson comorbidity scoring system without age weighting, the Katz index of independence in activities of daily living, and the Lawton instrumental activities of daily living scale. The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurs first. OS will be measured as the time from the date of randomization to the date of death.
- Pharmacokinetic Parameter: Plasma Concentration of Ixazomib [Cycle 1 (1 and 4 hours post-dose Day 1, Days 8 and 15 pre-dose); Cycle 2 and 5 (Days 1 and 8 pre-dose) and Cycles 3, 4, 6-10 (Day 1 pre-dose) (Cycle length =28 days)]
Plasma concentrations of the complete hydrolysis product of ixazomib citrate (ixazomib) will be measured using a validated Liquid Chromatography-tandem Mass Spectrometry (LC/MS/MS) assay.
- Time to Resolution of Peripheral Neuropathy (PN) Events [From the initial onset date of PN up to the resolution date for resolved events (Up to 25 Months)]
PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the Medical Dictionary for Regulatory Activities (MedDRA). A PN event is considered as resolved if its final outcome is resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. Time to resolution is defined as the time from the initial onset date (inclusive) to the resolution date for resolved events.
- Time to Improvement of PN Events [From the initial onset date of PN up to the improvement of event (Up to 25 Months)]
PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies NEC according to the MedDRA. A PN event is considered as resolved if its final outcome is resolved with no subsequent PN event of the same preferred term occurring on the improvement date or the day before and after. Time to improvement is defined as the time from the initial onset date (inclusive) to the improvement of event.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic newly diagnosed multiple myeloma (NDMM) according to standard criteria.
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Completed 6 to 12 months (± 2 weeks) of initial therapy, during which the participant was treated to best response, defined as the best response maintained for 2 cycles after the M-protein nadir is reached.
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Documented major response (PR, VGPR, CR) according to the International Myeloma Working Group (IMWG) uniform response criteria, version 2011, after this initial therapy.
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Female participants who:
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Are postmenopausal for at least 1 year before the screening visit, OR
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Are surgically sterile, OR
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If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, OR
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Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
Male participants, even if surgically sterilized (that is, status postvasectomy), who:
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Agree to practice effective barrier contraception during the entire study Treatment period and through 90 days after the last dose of study drug, OR
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Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
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Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
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Complete documentation of the details of the initial therapy before randomization including cytogenetics and International Staging System (ISS) is available.
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Eastern Cooperative Oncology Group Performance Status of 0 to 2.
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Suitable venous access for the study-required blood sampling and consent for the specific amounts that will be taken.
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Is willing and able to adhere to the study visit schedule and other protocol requirements including blood sampling and bone marrow aspiration.
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Must meet the following clinical laboratory criteria at study entry:
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Absolute neutrophil count (ANC) greater than or equal to (≥) 1,000 per cubic millimeter (/mm3) without growth factor support and platelet count ≥75,000/mm3. Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days before randomization.
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Total bilirubin less than or equal to (≤) 1.5*the upper limit of the normal range (ULN).
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Alanine aminotransferase and aspartate aminotransferase ≤ 3*ULN.
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Calculated creatinine clearance ≥ 30 milliliter per minute (mL/min) (using the Cockcroft-Gault equation).
Exclusion Criteria:
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Multiple myeloma that has relapsed after, or was not responsive to, initial therapy.
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Prior SCT.
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Radiotherapy within 14 days before randomization.
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Diagnosed or treated for another malignancy within 5 years before randomization or previous diagnosis with another malignancy. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
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Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
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Major surgery within 14 days before randomization.
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Central nervous system involvement.
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Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before randomization.
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Diagnosis of Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome (POEMS), plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
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Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, uncontrolled congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
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Systemic treatment with strong cytochrome P450 3A (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or St. John's wort within 14 days before randomization.
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Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active hepatitis B or C infection.
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Comorbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (example, PN that is Grade 1 with pain or Grade 2 or higher of any cause).
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Psychiatric illness or social situation that would limit compliance with study requirements.
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Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
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Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment.
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Treatment with any investigational products within 30 days before randomization.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Robert A Moss MD FACP Inc | Fountain Valley | California | United States | 92708 |
| 2 | UCLA Medical Hematology and Oncology | Los Angeles | California | United States | 90095 |
| 3 | North County Oncology Medical Clinic Inc | Oceanside | California | United States | 92056 |
| 4 | Ventura County Hematology Oncology Specialists | Oxnard | California | United States | 93030 |
| 5 | Emad Ibrahim, MD, Inc | Redlands | California | United States | 92373 |
| 6 | Global Cancer Research Institute (GCRI), Inc. | San Jose | California | United States | 95124 |
| 7 | Central Coast Medical Oncology Corporation | Santa Maria | California | United States | 93454 |
| 8 | Winship Cancer Institute, Emory University | Atlanta | Georgia | United States | 30322 |
| 9 | John H. Stroger Jr. Hospital of Cook County | Chicago | Illinois | United States | 60612 |
| 10 | Siouxland Hematology - Oncology Associates LLP | Sioux City | Iowa | United States | 51101 |
| 11 | Appalachian Regional Healthcare | Hazard | Kentucky | United States | 41701 |
| 12 | New England Cancer Specialists | Scarborough | Maine | United States | 04074 |
| 13 | Saint Agnes Hospital - Baltimore - Hunt - PPDS | Baltimore | Maryland | United States | 21229 |
| 14 | University Hospital of Wales - | Bethesda | Maryland | United States | 20817 |
| 15 | Tufts Medical Center - PPDS | Boston | Massachusetts | United States | 02111 |
| 16 | Herbert-Herman Cancer Center | Lansing | Michigan | United States | 48912 |
| 17 | Clinical Research Alliance Inc | New York | New York | United States | 10021 |
| 18 | New York Presbyterian Hospital - Weill-Cornell | New York | New York | United States | 10021 |
| 19 | Cancer Care of WNC PA | Asheville | North Carolina | United States | 28801 |
| 20 | UPMC Cancer Pavillion | Pittsburgh | Pennsylvania | United States | 15232 |
| 21 | HOPE Cancer Center of East Texas | Tyler | Texas | United States | 75701 |
| 22 | Swedish Cancer Institute | Seattle | Washington | United States | 98109 |
| 23 | W VA University Mary Babb Randolph Cancer Center | Morgantown | West Virginia | United States | 26506 |
| 24 | Hospital Universitario Austral | Buenos Aires | Ciudad Autonoma De BuenosAires | Argentina | B1629AHJ |
| 25 | Hospital Italiano de Buenos Aires | Buenos Aires | Ciudad Autonoma De BuenosAires | Argentina | C1181ACH |
| 26 | Centro de Educacion Medica e Investigaciones Clinicas "Norberto Quirno" (CEMIC) | Buenos Aires | Ciudad Autonoma De BuenosAires | Argentina | C1431FWO |
| 27 | Sanatorio Allende S.A. | Cordoba | Argentina | X5000JHQ | |
| 28 | Hospital Iturraspe | Santa Fe | Argentina | S3000ADL | |
| 29 | St Vincents Hospital Melbourne - PPDS | Fitzroy | Victoria | Australia | 3065 |
| 30 | Frankston Hospital | Frankston | Victoria | Australia | 3199 |
| 31 | The Alfred Hospital | Melbourne | Victoria | Australia | 3004 |
| 32 | Universitatsklinikum Innsbruck | Innsbruck | Tirol | Austria | 6020 |
| 33 | Paracelsus Medizinische Privatuniversitat | Salzburg | Austria | 5020 | |
| 34 | Klinikum Wels-Grieskirchen GmbH | Wels | Austria | 4600 | |
| 35 | Medizinische Universitat Wien (Medical University of Vienna) | Wien | Austria | A-1090 | |
| 36 | Universitair Ziekenhuis Brussel - PIN | Brussel | Brussels | Belgium | 1090 |
| 37 | UZ Brussel | Brussel | Brussels | Belgium | 1090 |
| 38 | Cliniques Universitaires Saint-Luc | Bruxelles | Brussels | Belgium | 1200 |
| 39 | Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet | Salvador | Bahia | Brazil | 41253-196 |
| 40 | Hospital Das Clinicas Da Universidade Federal de Goias | Goiania | Goias | Brazil | 74605-020 |
| 41 | Hospital Das Clinicas Da UFMG | Belo Horizonte | Minas Gerais | Brazil | 30130-100 |
| 42 | Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner | Curitiba | Parana | Brazil | 81520-060 |
| 43 | Liga Norte Riograndense Contra O Cancer | Natal | Rio Grande Do Norte | Brazil | 59040-150 |
| 44 | Universidade de Caxias do Sul | Caxias Do Sul | Rio Grande Do Sul | Brazil | 95070-560 |
| 45 | Associacao Hospital de Caridade Ijui | Ijui | Rio Grande Do Sul | Brazil | 98700-000 |
| 46 | American Oncology Partners of Maryland, PA | Passo Fundo | Rio Grande Do Sul | Brazil | 99010-260 |
| 47 | Hospital Moinhos de Vento | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-001 |
| 48 | Hospital de Clinicas de Porto Alegre (HCPA) - PPDS | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-903 |
| 49 | Mae de Deus Center Hospital Giovanni Battista | Porto Alegre | Rio Grande Do Sul | Brazil | 90470-340 |
| 50 | Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS) | Porto Alegre | Rio Grande Do Sul | Brazil | 90610-000 |
| 51 | Instituto Joinvilense de Hematologia E Oncologia | Joinville | Santa Catarina | Brazil | 89201260 |
| 52 | Fundacao PIO XII | Barretos | Sao Paulo | Brazil | 14784-400 |
| 53 | Universidade Estadual de Campinas | Campinas | Sao Paulo | Brazil | 13083-878 |
| 54 | Hospital Amaral Carvalho | Jau | Sao Paulo | Brazil | 17210-120 |
| 55 | Faculdade de Medicina Do ABC | Santo Andre | Sao Paulo | Brazil | 09060-650 |
| 56 | HEMORIO - Unidade de Pesquisa Clinica | Rio De Janeiro | Brazil | 20211-030 | |
| 57 | Instituto Nacional de Cancer | Rio de Janeiro | Brazil | 20231-050 | |
| 58 | Fundação Antônio Prudente - AC Camargo Câncer Center | Rio De Janeiro | Brazil | 21941-913 | |
| 59 | Hospital de Base Da Faculdade de Medicina de Sao Jose Do Rio Preto | Sao Jose Do Rio Preto | Brazil | 15090-000 | |
| 60 | Instituto de Ensino E Pesquisa Sao Lucas | Sao Paulo | Brazil | 01236-030 | |
| 61 | Hospital Sirio Libanes | Sao Paulo | Brazil | 01308-050 | |
| 62 | Ealing Hospital | Sao Paulo | Brazil | 01509-900 | |
| 63 | Clinica Sao Germano | Sao Paulo | Brazil | 04537-080 | |
| 64 | Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo | Sao Paulo | Brazil | 05403-000 | |
| 65 | Hospital Israelita Albert Einstein | Sao Paulo | Brazil | 05652-900 | |
| 66 | Hospital Santa Marcelina | Sao Paulo | Brazil | 08270-070 | |
| 67 | Royal Victoria Regional Health Centre | Barrie | Ontario | Canada | L4M 6M2 |
| 68 | William Osler Health Centre | Brampton | Ontario | Canada | L6W 3J7 |
| 69 | Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 2M9 |
| 70 | McGill University Health Center | Montreal | Quebec | Canada | H4A 3J1 |
| 71 | Hospital Amaral Carvalho | Temuco | Araucanía | Chile | 4800827 |
| 72 | Instituto Nacional Del Cancer | Santiago | Chile | 8380455 | |
| 73 | Centro Internacional de Estudios Clinicos | Santiago | Chile | ||
| 74 | Centro de Investigaciones Clinicas Vina del Mar | Vina Del Mar | Chile | 2570017 | |
| 75 | Hospital de Clinicas de Passo Fundo | Nanjing | Jiangsu | China | 210029 |
| 76 | Ruijin Hospital Shanghai Jiaotong University School of Medicine | Shanghai | Shanghai | China | 200025 |
| 77 | The First Affiliated Hospital, College of Medicine, Zhejiang University | Hangzhou | Zhejiang | China | 310003 |
| 78 | Beijing Chaoyang Hospital Capital Medical University | Beijing | China | 100020 | |
| 79 | Peking University Third Hospital | Beijing | China | 100191 | |
| 80 | Peking Union Medical College Hospital | Beijing | China | ||
| 81 | The First Affiliated Hospital, College of Medicine, Zhejiang University | Hangzhou | China | 310003 | |
| 82 | Renji Hospital Shanghai Jiaotong University School of Medicine | Shanghai | China | 200001 | |
| 83 | Shanghai Chang Zheng Hospital | Shanghai | China | 200003 | |
| 84 | Hospital São Rafael | Shenyang | China | 110004 | |
| 85 | Second Hospital of Shanxi Medical University | Taiyuan | China | 030001 | |
| 86 | James Lind Centro de Investigación del Cáncer | Wuhan | China | 430030 | |
| 87 | Hospital Pablo Tobon Uribe | Medellin | Antioquia | Colombia | 050034 |
| 88 | Instituto Nacional de Cancerologia Colombia | Bogota | Cundinamarca | Colombia | |
| 89 | Hospital Universitario San Ignacio | Bogota | Distrito Capital De Bogota | Colombia | 110311 |
| 90 | Clinical Hospital Dubrava | Zagreb | Grad Zagreb | Croatia | 10000 |
| 91 | Clinical Hospital Center Rijeka | Rijeka | Croatia | 51000 | |
| 92 | Clinical Hospital Center Zagreb - PPDS | Zagreb | Croatia | 10 000 | |
| 93 | Fakultni nemocnice Hradec Kralove | Hradec Kralove | Kralovehradeck Kraj | Czechia | 500 05 |
| 94 | Fakultni nemocnice Kralovske Vinohrady | Prague | Praha, Hlavni Mesto | Czechia | 100 34 |
| 95 | Fakultni nemocnice Brno | Brno | Czechia | 625 00 | |
| 96 | Fakultni nemocnice Olomouc | Olomouc | Czechia | 775 20 | |
| 97 | Fakultni nemocnice Ostrava | Ostrava | Czechia | 708 52 | |
| 98 | Vseobecna fakultni nemocnice v Praze | Praha 2 | Czechia | 128 08 | |
| 99 | Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University) | København | Capital | Denmark | 2100 |
| 100 | Aarhus Universitetshospital Århus Sygehus | Aarhus N | Denmark | DK-8200 | |
| 101 | Regionshospitalet Holstebro | Holstebro | Denmark | 7500 | |
| 102 | Odense Universitetshospital | Odense | Denmark | 5000 | |
| 103 | Hopital Antoine Beclere | Clamart | Hauts-de-Seine | France | 92140 |
| 104 | Hotel Dieu | Nantes | Loire-Atlantique | France | 44093 |
| 105 | CHRU Nancy | Vandoeuvre-les-nancy | Meurthe-et-Moselle | France | 54511 |
| 106 | CHRU Dijon Complexe Du Bocage | Dijon | France | 21079 | |
| 107 | Hopital Saint Vincent de Paul GHICL | Lille | France | 59020 | |
| 108 | CHRU Lille | Lille | France | 59037 | |
| 109 | Hopital de la Pitie Salpetriere | Paris | France | 75013 | |
| 110 | Groupe Hospitalier Necker Enfants Malades | Paris | France | 75015 | |
| 111 | Hopital Haut Leveque | Pessac | France | 33604 | |
| 112 | Hopital Jean Bernard | Poitiers | France | 86021 | |
| 113 | CHRU Rennes | Rennes | France | ||
| 114 | Universitatsklinikum Ulm | Ulm | Baden-Wurttemberg | Germany | 89081 |
| 115 | Schwarzwald Baar Klinkum Villingen-Schwenningen GmbH | Villingen-Schwenningen | Baden-Wurttemberg | Germany | 78050 |
| 116 | Hamatologische Onkologische Gemeinschaftspraxis Dr. Brudler, Dr. Heinrich, Dr. Bangerter | Augsburg | Bayern | Germany | 86150 |
| 117 | Internistisch Hamatologische und Internistische Praxis | Herrsching am Ammersee | Bayern | Germany | 82211 |
| 118 | LMU Klinikum der Universitat Munchen | Munchen | Bayern | Germany | 81377 |
| 119 | Pius Hospital Oldenburg | Oldenburg | Niedersachsen | Germany | 26121 |
| 120 | Universitatsklinikum Essen | Essen | Nordrhein-Westfalen | Germany | 45122 |
| 121 | Gemeinschaftspraxis fur Hamatologie und Onkologie | Munster | Nordrhein-Westfalen | Germany | 48149 |
| 122 | Universitatsmedizin der Johannes Gutenberg-Universitat Mainz | Mainz | Rheinland-Pfalz | Germany | 55131 |
| 123 | Universitat Des Saarlandes | Homburg | Saarland | Germany | 66421 |
| 124 | Onkologie Aschaffenburg | Aschaffenburg | Germany | 63739 | |
| 125 | Charite - Universitatsmedizin Berlin | Berlin | Germany | 12200 | |
| 126 | Medizinisches Versorgungszentrum Onkologischer Schwerpunkt | Berlin | Germany | 14195 | |
| 127 | Klinikum Landshut | Landshut | Germany | 84034 | |
| 128 | Klinikum rechts der Isar der Technischen Universitat Munchen | Munchen | Germany | 81675 | |
| 129 | Praxis Pihusch Medizinisches Versorgungszentrum GbR | Rosenheim | Germany | 83022 | |
| 130 | Gemeinschaftspraxis Dr. med. R. Schlag & Dr. med. B. Schottker & Dr. med. J. Haas | Wurzburg | Germany | 97080 | |
| 131 | University of Athens Medical School - Regional General Hospital Alexandra | Athens | Attiki | Greece | 115 28 |
| 132 | Evangelismos General Hospital of Athens | Athens | Greece | 10676 | |
| 133 | University General Hospital of Ioannina | Ioannina | Greece | 45500 | |
| 134 | University General Hospital of Larissa | Larissa | Greece | 41110 | |
| 135 | Theageneio Anticancer Oncology Hospital of Thessaloniki | Thessaloniki | Greece | 54007 | |
| 136 | Georgios Papanikolaou General Hospital of Thessaloniki | Thessaloniki | Greece | 57010 | |
| 137 | Semmelweis Egyetem | Budapest | Hungary | 1083 | |
| 138 | Klinika Hematologii, Szpital Uniwersytecki Nr 2 im. Jana Biziela w Bydgoszczy | Budapest | Hungary | 1097 | |
| 139 | Debreceni Egyetem Klinikai Kozpont | Debrecen | Hungary | 4032 | |
| 140 | Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont | Szeged | Hungary | 6725 | |
| 141 | Shamir Medical Center Assaf Harofeh | Be'er Sheva | Israel | 84101 | |
| 142 | Rigshospitalet | Beer Yaakov | Israel | 70300 | |
| 143 | Bnai Zion Medical Center | Haifa | Israel | 33394 | |
| 144 | Hadassah Medical Center - PPDS | Jerusalem | Israel | 91120 | |
| 145 | Meir Medical Center | Kfar Saba | Israel | 44281 | |
| 146 | Rabin Medical Center - PPDS | Petah Tikva | Israel | 49100 | |
| 147 | Chaim Sheba Medical Center | Ramat Gan | Israel | 52621 | |
| 148 | Tel Aviv Sourasky Medical Center | Tel Aviv | Israel | 64239 | |
| 149 | Assuta Medical Centers | Tel Aviv | Israel | 69710 | |
| 150 | Baruch Padeh Poriya Medical Center | Tiberias | Israel | 15208 | |
| 151 | AORN A Cardarelli | Napoli | Campania | Italy | 80131 |
| 152 | Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi | Bologna | Emilia-Romagna | Italy | 40138 |
| 153 | Ospedale Infermi di Rimini | Rimini | Emilia-Romagna | Italy | 47900 |
| 154 | IRCCS Az. Osp. Universitaria San Martino- IST | Genova | Liguria | Italy | 16132 |
| 155 | ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN | Brescia | Lombardia | Italy | 25123 |
| 156 | ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda | Milano | Lombardia | Italy | 20162 |
| 157 | Ospedale Casa Sollievo Della Sofferenza IRCCS | San Giovanni Rotondo | Puglia | Italy | 71013 |
| 158 | Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele | Catania | Sicilia | Italy | 95124 |
| 159 | Azienda Ospedaliero Universitaria Pisana | Pisa | Toscana | Italy | 56216 |
| 160 | Azienda Ospedaliera S Maria Di Terni | Terni | Umbria | Italy | 05100 |
| 161 | Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi | Ancona | Italy | 60126 | |
| 162 | Azienda Ospedaliera Universitaria Careggi | Firenze | Italy | 50139 | |
| 163 | Azienda Ospedaliero Universitaria di Parma | Parma | Italy | 43126 | |
| 164 | Ospedale Santa Maria Delle Croci | Ravenna | Italy | 48100 | |
| 165 | Azienda Ospedaliera Citta della Salute e della Scienza di Torino | Torino | Italy | 10126 | |
| 166 | Ogaki Municipal Hospital | Ogaki | Gihu | Japan | 503-8502 |
| 167 | Kobe City Medical Center General Hospital | Kobe-City | Hyogo | Japan | 650-0047 |
| 168 | Hitachi General Hospital | Hitachi | Ibaraki | Japan | 317-0077 |
| 169 | Nara Hospital Kinki University Faculty of Medicine | Ikoma-City | Nara | Japan | 630-0293 |
| 170 | National Hospital Organization Okayama Medical Center | Okayama-city | Okayama | Japan | 701-1192 |
| 171 | Juntendo University Hospital | Bunkyo | Tokyo | Japan | 113-8431 |
| 172 | Japanese Red Cross Medical Center | Shibuya-ku | Tokyo | Japan | 150-8935 |
| 173 | National Hospital Organization Kyushu Medical Center | Fukuoka | Japan | 810-8563 | |
| 174 | Fukushima Medical University Hospital | Fukushima-City | Japan | 960-1295 | |
| 175 | National Hospital Organization Mito Medical Center | Ibaraki | Japan | 311-3193 | |
| 176 | Kurume University Hospital | Kurume | Japan | 830-0011 | |
| 177 | Shizuoka Cancer Center | Nagaizumi-chō | Japan | 4118777 | |
| 178 | Japanese Red Cross Nagoya Daiichi Hospital | Nagoya | Japan | 453-8511 | |
| 179 | Nagoya City University Hospital | Nagoya | Japan | 467-8602 | |
| 180 | Japanese Red Cross Narita Hospital | Narita-shi | Japan | 286-8523 | |
| 181 | Niigata Cancer Center Hospital | Niigata-city | Japan | ||
| 182 | Osaka Saiseikai Nakatsu Hospital | Osaka | Japan | 530-0012 | |
| 183 | National Hospital Organization Disaster Medical Center | Tachikawa | Japan | 1900014 | |
| 184 | Toyohashi Municipal Hospital | Toyohashi | Japan | ||
| 185 | Yamanashi Prefectural Central Hospital | Yamanashi | Japan | 400-8506 | |
| 186 | National Cancer Center | Goyang-si | Gyeonggido | Korea, Republic of | 10408 |
| 187 | Gachon University Gil Medical Center | Incheon | Korea, Republic of | 405-760 | |
| 188 | Seoul National University Hospital | Seoul | Korea, Republic of | 110-744 | |
| 189 | Severance Hospital Yonsei University Health System - PPDS | Seoul | Korea, Republic of | 120-752 | |
| 190 | Samsung Medical Center - PPDS | Seoul | Korea, Republic of | 135-710 | |
| 191 | The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | Korea, Republic of | 137-701 | |
| 192 | Centro de Investigacion Farmaceutica Especializada de Occidente, SC - PPDS | Guadalajara | Jalisco | Mexico | 44160 |
| 193 | Hospital Y Clinica OCA Sociedad Anonima de Capital Variable | Monterrey | Nuevo Leon | Mexico | 64000 |
| 194 | Hospital Universitario Dr. Jose Eleuterio Gonzalez | Monterrey | Nuevo Leon | Mexico | 64460 |
| 195 | Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran | Mexico City | Mexico | 14000 | |
| 196 | Oaxaca Site management Organization (OSMO) - PPDS | Oaxaca | Mexico | 68000 | |
| 197 | Shengjing Hospital of China Medical University | Bydgoszcz | Kujawsko-pomorskie | Poland | 85-168 |
| 198 | MTZ Clinical Research Sp z o o - PRATIA - PPDS | Warszawa | Mazowieckie | Poland | 02-106 |
| 199 | Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich | Chorzow | Poland | ||
| 200 | Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu | Wroclaw | Poland | 50-367 | |
| 201 | Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. | Lisbon | Lisboa | Portugal | 1099-023 |
| 202 | Hospital Garcia de Orta | Almada | Portugal | 2801-951 | |
| 203 | Hospital de Braga | Braga | Portugal | 4710-243 | |
| 204 | Champalimaud Cancer Center | Lisboa | Portugal | 1400-038 | |
| 205 | Centro Hospitalar do Porto - Hospital de Santo Antonio | Porto | Portugal | 4099-001 | |
| 206 | Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS | Porto | Portugal | 4200-072 | |
| 207 | Centro Hospitalar de Sao Joao EPE | Porto | Portugal | 4200-319 | |
| 208 | State Medical and Preventive Treatment Institution Kirov Regional Clinical Oncology Dispensary | Kirov | Russian Federation | 610027 | |
| 209 | Stavropol Regional Clinical Oncology Centre Pyatigorsk Affiliate | Pyatigorsk | Russian Federation | 357500 | |
| 210 | Ryazan Regional Clinical Hospital | Ryazan | Russian Federation | 390039 | |
| 211 | Russian Research Institute of Hematology and Blood Transfusion | St. Petersburg | Russian Federation | 193024 | |
| 212 | City Center of MS Treatment based on Saint-Petersburg City Clinical Hospital #31 | St. Petersburg | Russian Federation | 197110 | |
| 213 | Tongji Hospital Tongji Medical College Huazhong University of Science and Technology | Belgrade | Serbia | 11000 | |
| 214 | Clinical Hospital Center ''Bezanijska Kosa'' | Belgrade | Serbia | 11080 | |
| 215 | University Clinical Center Kragujevac | Kragujevac | Serbia | 34000 | |
| 216 | Soroka University Medical Centre | Nis | Serbia | 18000 | |
| 217 | National University Hospital | Singapore | Singapore | 119074 | |
| 218 | Singapore General Hospital (SGH) | Singapore | Singapore | 169608 | |
| 219 | Medical Oncology Centre of Rosebank | Johannesburg | Gauteng | South Africa | 2196 |
| 220 | Albert Alberts Stem Cell Transplant Centre | Pretoria | Gauteng | South Africa | 0044 |
| 221 | Mary Potter Oncology Centre | Pretoria | Gauteng | South Africa | 0181 |
| 222 | Hospital Universitario Germans Trias i Pujol | Badalona | Barcelona | Spain | 08916 |
| 223 | Hospital Universitario Quironsalud Madrid | Pozuelo De Alarcon | Madrid, Communidad Delaware | Spain | 28223 |
| 224 | Clinica Universidad Navarra | Pamplona | Navarra | Spain | 31008 |
| 225 | Hospital Clinic de Barcelona | Barcelona | Spain | 08036 | |
| 226 | Hospital de La Santa Creu i Sant Pau | Barcelona | Spain | 08041 | |
| 227 | Hospital Universitario de La Princesa | Madrid | Spain | 28006 | |
| 228 | Hospital General Universitario Gregorio Maranon | Madrid | Spain | 28009 | |
| 229 | Hospital Universitario Infanta Leonor | Madrid | Spain | 28031 | |
| 230 | Hospital Universitario La Paz | Madrid | Spain | 28046 | |
| 231 | Hospital Universitario HM Sanchinarro CIOCC | Madrid | Spain | 28050 | |
| 232 | Hospital General Universitario Morales Meseguer | Murcia | Spain | 30008 | |
| 233 | Complejo Asistencial Universitario de Salamanca H. Clinico | Salamanca | Spain | 37007 | |
| 234 | Hospital Universitari i Politecnic La Fe de Valencia | Valencia | Spain | 46026 | |
| 235 | Karolinska Universitetssjukhuset Huddinge | Stockholm | Sodermanlands Lan | Sweden | |
| 236 | Karolinska Universitetssjukhuset Solna | Stockholm | Sodermanlands Lan | Sweden | |
| 237 | Sahlgrenska Universitetssjukhuset | Goteborg | Vastra Gotalands Lan | Sweden | |
| 238 | Skanes Universitetssjukhus Lund | Lund | Sweden | SE-22185 | |
| 239 | Spital STS AG | Thun | Switzerland | CH-3600 | |
| 240 | Kaohsiung Medical University Hospital | Kaohsiung | Taiwan | 807 | |
| 241 | Taichung Veterans General Hospital | Taichung | Taiwan | 40705 | |
| 242 | National Taiwan University Hospital | Taipei | Taiwan | 100 | |
| 243 | Ramathibodi Hospital | Bangkok | Krung Thep Maha Nakhon | Thailand | 10400 |
| 244 | Chulalongkorn University | Bangkok | Thailand | 10330 | |
| 245 | Maharaj Nakorn Chiang Mai Chiang Mai University | Chiangmai | Thailand | 50200 | |
| 246 | Hacettepe Universitesi Tip Fakultesi Hastanesi | Ankara | Turkey | 06100 | |
| 247 | Ankara University Medical Faculty PPDS | Ankara | Turkey | 06590 | |
| 248 | Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi | Istanbul | Turkey | 34093 | |
| 249 | Dokuz Eylul University Medical Faculty | Izmir | Turkey | 35340 | |
| 250 | Belfast City Hospital | Belfast | Antrim | United Kingdom | BT9 7AB |
| 251 | Birmingham Heartlands Hospital | West Malling | Birmingham | United Kingdom | B9 5SS |
| 252 | Bristol Haematology and Oncology Centre | Bristol | Bristol, City Of | United Kingdom | BS2 8ED |
| 253 | Royal Bournemouth Hospital | Bournemouth | Dorset | United Kingdom | BH7 7DW |
| 254 | Queen Alexandra Hospital | Portsmouth | Hampshire | United Kingdom | PO6 3LY |
| 255 | Kent and Canterbury Hospital | Canterbury | Kent | United Kingdom | CT1 3NG |
| 256 | Barts Health NHS Trust | London | London, City Of | United Kingdom | EC1A 7BE |
| 257 | University College London | London | London, City Of | United Kingdom | NW1 2BU |
| 258 | Kings College Hospital | London | London, City Of | United Kingdom | SE5 9RS |
| 259 | Hammersmith Hospital | London | London, City Of | United Kingdom | W12 0HS |
| 260 | Hillingdon Hospital | Uxbridge | London, City Of | United Kingdom | UB8 3NN |
| 261 | Churchill Hospital | Oxford | Oxfordshire | United Kingdom | OX3 7LJ |
| 262 | New Cross Hospital | Wolverhampton | Staffordshire | United Kingdom | WV10 0QP |
| 263 | Royal Marsden Hospital - Surrey | Sutton | Surrey | United Kingdom | SM2 5PT |
| 264 | Royal United Hospital | Bath | United Kingdom | BA1 3NG | |
| 265 | Ulster Hospital | Belfast | United Kingdom | BT16 1RH | |
| 266 | Southmead Hospital | Bristol | United Kingdom | BS10 5NB | |
| 267 | University Clinical Center Nis | Cardiff | United Kingdom | CF14 4XW | |
| 268 | West Middlesex University Hospital | Isleworth | United Kingdom | TW7 6AF | |
| 269 | Leicester Royal Infirmary | Leicester | United Kingdom | LE1 5WW | |
| 270 | Chelsea and Westminster NHS Trust | London | United Kingdom | ||
| 271 | Manchester Royal Infirmary - PPDS | Manchester | United Kingdom | M13 9WL | |
| 272 | Northwick Park Hospital | Middlesex | United Kingdom | HA1 3UJ | |
| 273 | The Royal Oldham Hospital - PPDS | Oldham | United Kingdom | OL1 2JH | |
| 274 | University Clinical Center of Serbia - PPDS | Southall | United Kingdom | UB1 3HW | |
| 275 | Singleton Hospital - PPDS | Swansea | United Kingdom |
Sponsors and Collaborators
- Takeda
Investigators
- Study Director: Study Director, Takeda
Study Documents (Full-Text)
More Information
Publications
None provided.- C16021
- U1111-1160-1702
- 2014-001394-13
- REec-2015-1414
- JapicCTI-152873
- 153300410A0048
- 1046003327
- SNCTP000001745
- 15/NE/0167
- 182602
- MOH_2017-06-15_000529
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 187 investigative sites worldwide from 09 April 2015 to data cut-off: 12 Aug 2019. This study is ongoing. |
|---|---|
| Pre-assignment Detail | Participants with newly diagnosed multiple myeloma not treated with stem cell transplantation (SCT) were enrolled and randomized in 3:2 ratio to receive ixazomib or placebo respectively. |
| Arm/Group Title | Placebo | Ixazomib |
|---|---|---|
| Arm/Group Description | Ixazomib placebo-matching capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib placebo-matching capsules, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019). | Ixazomib 3 mg, capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib 3 or 4 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019). |
| Period Title: Overall Study | ||
| STARTED | 281 | 425 |
| COMPLETED | 30 | 66 |
| NOT COMPLETED | 251 | 359 |
Baseline Characteristics
| Arm/Group Title | Placebo | Ixazomib | Total |
|---|---|---|---|
| Arm/Group Description | Ixazomib placebo-matching capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib placebo-matching capsules, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019). | Ixazomib 3 mg, capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib 3 or 4 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019). | Total of all reporting groups |
| Overall Participants | 281 | 425 | 706 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
72.8
(6.77)
|
72.3
(6.87)
|
72.5
(6.83)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
126
44.8%
|
203
47.8%
|
329
46.6%
|
| Male |
155
55.2%
|
222
52.2%
|
377
53.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
36
12.8%
|
46
10.8%
|
82
11.6%
|
| Not Hispanic or Latino |
237
84.3%
|
366
86.1%
|
603
85.4%
|
| Unknown or Not Reported |
8
2.8%
|
13
3.1%
|
21
3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
227
80.8%
|
330
77.6%
|
557
78.9%
|
| Black or African American |
5
1.8%
|
15
3.5%
|
20
2.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
0.2%
|
1
0.1%
|
| Asian |
39
13.9%
|
63
14.8%
|
102
14.4%
|
| American Indian or Alaska Native |
1
0.4%
|
1
0.2%
|
2
0.3%
|
| Other |
5
1.8%
|
9
2.1%
|
14
2%
|
| Not Reported |
4
1.4%
|
6
1.4%
|
10
1.4%
|
| Region of Enrollment (Count of Participants) | |||
| Australia |
11
3.9%
|
9
2.1%
|
20
2.8%
|
| China |
3
1.1%
|
6
1.4%
|
9
1.3%
|
| Japan |
15
5.3%
|
17
4%
|
32
4.5%
|
| Singapore |
4
1.4%
|
8
1.9%
|
12
1.7%
|
| Korea, Republic Of |
10
3.6%
|
17
4%
|
27
3.8%
|
| Taiwan, Province Of China |
3
1.1%
|
5
1.2%
|
8
1.1%
|
| Thailand |
2
0.7%
|
8
1.9%
|
10
1.4%
|
| Austria |
2
0.7%
|
3
0.7%
|
5
0.7%
|
| Belgium |
0
0%
|
1
0.2%
|
1
0.1%
|
| Czech Republic |
31
11%
|
38
8.9%
|
69
9.8%
|
| Denmark |
1
0.4%
|
5
1.2%
|
6
0.8%
|
| France |
10
3.6%
|
6
1.4%
|
16
2.3%
|
| Germany |
5
1.8%
|
6
1.4%
|
11
1.6%
|
| Greece |
50
17.8%
|
63
14.8%
|
113
16%
|
| Hungary |
5
1.8%
|
7
1.6%
|
12
1.7%
|
| Israel |
5
1.8%
|
11
2.6%
|
16
2.3%
|
| Italy |
18
6.4%
|
34
8%
|
52
7.4%
|
| Poland |
2
0.7%
|
13
3.1%
|
15
2.1%
|
| Portugal |
6
2.1%
|
10
2.4%
|
16
2.3%
|
| Russia |
2
0.7%
|
6
1.4%
|
8
1.1%
|
| Serbia |
11
3.9%
|
13
3.1%
|
24
3.4%
|
| South Africa |
2
0.7%
|
5
1.2%
|
7
1%
|
| Spain |
23
8.2%
|
25
5.9%
|
48
6.8%
|
| Sweden |
3
1.1%
|
3
0.7%
|
6
0.8%
|
| Switzerland |
1
0.4%
|
1
0.2%
|
2
0.3%
|
| Turkey |
4
1.4%
|
8
1.9%
|
12
1.7%
|
| United Kingdom |
20
7.1%
|
46
10.8%
|
66
9.3%
|
| Argentina |
2
0.7%
|
2
0.5%
|
4
0.6%
|
| Brazil |
16
5.7%
|
27
6.4%
|
43
6.1%
|
| Chile |
4
1.4%
|
7
1.6%
|
11
1.6%
|
| Colombia |
1
0.4%
|
2
0.5%
|
3
0.4%
|
| Canada |
4
1.4%
|
3
0.7%
|
7
1%
|
| Mexico |
2
0.7%
|
4
0.9%
|
6
0.8%
|
| United States |
3
1.1%
|
6
1.4%
|
9
1.3%
|
Outcome Measures
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first. Per IMWG criteria, PD definition: increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/dl); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved FLC levels (absolute increase >10 mg/dl); or bone marrow plasma cell percentage (absolute plasma cell percentage ≥10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia (corrected serum calcium >11.5mg/dl). |
| Time Frame | From the randomization until progressive disease (PD) or death or data cut-off date (12 Aug 2019) (Up to approximately 42 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants who were randomized and had post-randomization data. |
| Arm/Group Title | Placebo | Ixazomib |
|---|---|---|
| Arm/Group Description | Ixazomib placebo-matching capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib placebo-matching capsules, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019). | Ixazomib 3 mg, capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib 3 or 4 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019). |
| Measure Participants | 281 | 425 |
| Median (95% Confidence Interval) [months] |
9.4
|
17.4
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS will be measured as the time from the date of randomization to the date of death. |
| Time Frame | From the date of randomization every 12 weeks after PD on next-line therapy until death (Up to approximately 76 to 104 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period |
|---|---|
| Description | Response will be assessed according to IMWG criteria. Best response includes PR, VGPR and CR. |
| Time Frame | Up to 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Progression (TTP) |
|---|---|
| Description | TTP is defined as the time from the date of randomization to the date of first documentation of PD, using IMWG criteria. |
| Time Frame | From the date of randomization to the date of first documented PD (Up to approximately 76 to 104 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Progression Free Survival 2 (PFS2) |
|---|---|
| Description | PFS2 is defined as the time from the date of randomization to objective PD on next-line treatment using IMWG criteria, or death due to any cause, whichever occurs first. |
| Time Frame | From the date of randomization to every 12 weeks until 2nd PD or death (Up to approximately 76 to 104 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Next Line Therapy (TTNT) |
|---|---|
| Description | TTNT is defined as the time from the date of randomization to the date of the first dose of next-line antineoplastic therapy. |
| Time Frame | From the date of randomization to the date of the first dose of the next-line of therapy (Up to approximately 76 to 104 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to End of the Next-line of Therapy After Study Treatment |
|---|---|
| Description | Time to end of the next line of therapy is defined as the time from the date of randomization to the date of last dose of the next line of antineoplastic therapy following study treatment. |
| Time Frame | From the date of randomization to the date of last dose of the next-line of therapy (Up to approximately 76 to 104 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Duration of Next-line Therapy |
|---|---|
| Description | Duration of next-line therapy is defined as the time from the date of the first dose of the line of antineoplastic therapy coming after study treatment to the date of the last dose. |
| Time Frame | From the date of the first dose of the line of antineoplastic therapy coming after study treatment to the date of the last dose (Up to approximately 76 to 104 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Percentage of Participants Who Develop A New Primary Malignancy |
|---|---|
| Description | |
| Time Frame | From the randomization date till death or termination of the study (Up to approximately 76 to 104 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Percentage of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative, or the Maintenance of MRD Negativity |
|---|---|
| Description | Bone marrow aspirates and blood samples will be sent to a central laboratory and will be assessed for MRD using flow cytometry. MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. |
| Time Frame | Screening, Cycle 13, and Cycle 26 (Cycle length is equal to [=] 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Correlation of MRD Status With PFS and OS |
|---|---|
| Description | PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurs first. OS will be measured as the time from the date of randomization to the date of death. |
| Time Frame | Screening, Cycle 13, and Cycle 26 (Cycle length=28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | OS in a High-risk Population |
|---|---|
| Description | High-risk population will include but not be limited to participants carrying deletion (del)17, t(4;14), t(14;16). OS will be measured as the time from the date of randomization to the date of death. |
| Time Frame | From the date of randomization to every 12 weeks after PD on next-line therapy until death (Up to approximately 76 to 104 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | PFS in a High-risk Population |
|---|---|
| Description | High-risk population will include but not be limited to participants carrying del17, t(4;14), t(14;16). PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause. |
| Time Frame | From the date of randomization to every 4 weeks during follow-up until PD or death (Up to approximately 76 to 104 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Eastern Cooperative Oncology Group (ECOG) Performance Status |
|---|---|
| Description | ECOG performance status assess participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory ( greater than [>] 50 percent [%] of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead. |
| Time Frame | Cycle 2 and every 28 days ( Up to 24 months) (Cycle length =28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Percentage of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) |
|---|---|
| Description | AEs are defined as any unfavourable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug. A SAE means any untoward medical occurrence that results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is considered medically significant. |
| Time Frame | First dose of study drug through 30 days after last dose of study drug (Up to 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) |
|---|---|
| Description | The EORTC QLQ-C30 is completed by the participant. The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best). |
| Time Frame | Baseline and every 28 days (Up to 24 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Number of Participants With Any Markedly Abnormal Standard Safety Laboratory Values |
|---|---|
| Description | Clinical laboratory evaluations will be performed by a central laboratory. The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. |
| Time Frame | From First dose date of study drug through 30 days after the last dose of study drug (Up to 25 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Correlation Between Frailty Status and PFS and OS |
|---|---|
| Description | Participant's frailty status is classified as fit, unfit or frail on the bases of 4 components: age, the Charlson comorbidity scoring system without age weighting, the Katz index of independence in activities of daily living, and the Lawton instrumental activities of daily living scale. The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurs first. OS will be measured as the time from the date of randomization to the date of death. |
| Time Frame | Up to approximately 76 to 104 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Pharmacokinetic Parameter: Plasma Concentration of Ixazomib |
|---|---|
| Description | Plasma concentrations of the complete hydrolysis product of ixazomib citrate (ixazomib) will be measured using a validated Liquid Chromatography-tandem Mass Spectrometry (LC/MS/MS) assay. |
| Time Frame | Cycle 1 (1 and 4 hours post-dose Day 1, Days 8 and 15 pre-dose); Cycle 2 and 5 (Days 1 and 8 pre-dose) and Cycles 3, 4, 6-10 (Day 1 pre-dose) (Cycle length =28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Resolution of Peripheral Neuropathy (PN) Events |
|---|---|
| Description | PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the Medical Dictionary for Regulatory Activities (MedDRA). A PN event is considered as resolved if its final outcome is resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. Time to resolution is defined as the time from the initial onset date (inclusive) to the resolution date for resolved events. |
| Time Frame | From the initial onset date of PN up to the resolution date for resolved events (Up to 25 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Time to Improvement of PN Events |
|---|---|
| Description | PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies NEC according to the MedDRA. A PN event is considered as resolved if its final outcome is resolved with no subsequent PN event of the same preferred term occurring on the improvement date or the day before and after. Time to improvement is defined as the time from the initial onset date (inclusive) to the improvement of event. |
| Time Frame | From the initial onset date of PN up to the improvement of event (Up to 25 Months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | From study start date up to data cut-off date (12 Aug 2019) (Approximately 53 months) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population included all participants who received at least 1 dose of ixazomib or placebo. Three participants assigned to placebo arm each received a single 3 mg dose of ixazomib. These participants were excluded from the placebo arm and included in the ixazomib arm in the safety population. | |||
| Arm/Group Title | Placebo | Ixazomib | ||
| Arm/Group Description | Ixazomib placebo-matching capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib placebo-matching capsules, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019). | Ixazomib 3 mg, capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib 3 or 4 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019). | ||
All Cause Mortality |
||||
| Placebo | Ixazomib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/276 (2.2%) | 11/426 (2.6%) | ||
Serious Adverse Events |
||||
| Placebo | Ixazomib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 46/276 (16.7%) | 94/426 (22.1%) | ||
| Blood and lymphatic system disorders | ||||
| Pancytopenia | 0/276 (0%) | 1/426 (0.2%) | ||
| Febrile neutropenia | 0/276 (0%) | 1/426 (0.2%) | ||
| Anaemia | 3/276 (1.1%) | 0/426 (0%) | ||
| Cardiac disorders | ||||
| Pericardial effusion | 0/276 (0%) | 2/426 (0.5%) | ||
| Coronary artery disease | 1/276 (0.4%) | 1/426 (0.2%) | ||
| Cardiac failure | 0/276 (0%) | 1/426 (0.2%) | ||
| Cardiac failure acute | 1/276 (0.4%) | 0/426 (0%) | ||
| Acute myocardial infarction | 0/276 (0%) | 1/426 (0.2%) | ||
| Myocardial infarction | 2/276 (0.7%) | 0/426 (0%) | ||
| Left ventricular dysfunction | 0/276 (0%) | 1/426 (0.2%) | ||
| Atrial tachycardia | 0/276 (0%) | 1/426 (0.2%) | ||
| Atrial flutter | 1/276 (0.4%) | 0/426 (0%) | ||
| Cardiac arrest | 0/276 (0%) | 1/426 (0.2%) | ||
| Bradycardia | 1/276 (0.4%) | 0/426 (0%) | ||
| Eye disorders | ||||
| Cataract | 0/276 (0%) | 1/426 (0.2%) | ||
| Uveitis | 1/276 (0.4%) | 0/426 (0%) | ||
| Gastrointestinal disorders | ||||
| Inguinal hernia | 0/276 (0%) | 3/426 (0.7%) | ||
| Vomiting | 2/276 (0.7%) | 3/426 (0.7%) | ||
| Diarrhoea | 0/276 (0%) | 2/426 (0.5%) | ||
| Abdominal pain | 0/276 (0%) | 2/426 (0.5%) | ||
| Abdominal pain upper | 0/276 (0%) | 1/426 (0.2%) | ||
| Gastrointestinal haemorrhage | 0/276 (0%) | 1/426 (0.2%) | ||
| Melaena | 0/276 (0%) | 1/426 (0.2%) | ||
| Chilaiditi's syndrome | 0/276 (0%) | 1/426 (0.2%) | ||
| Large intestine polyp | 0/276 (0%) | 1/426 (0.2%) | ||
| Gastritis | 0/276 (0%) | 1/426 (0.2%) | ||
| Gastric disorder | 0/276 (0%) | 1/426 (0.2%) | ||
| Gastrointestinal motility disorder | 0/276 (0%) | 1/426 (0.2%) | ||
| Intestinal haemorrhage | 0/276 (0%) | 1/426 (0.2%) | ||
| Rectal prolapse | 1/276 (0.4%) | 0/426 (0%) | ||
| Ascites | 1/276 (0.4%) | 0/426 (0%) | ||
| General disorders | ||||
| Non-cardiac chest pain | 0/276 (0%) | 2/426 (0.5%) | ||
| Chest pain | 0/276 (0%) | 1/426 (0.2%) | ||
| Pyrexia | 1/276 (0.4%) | 2/426 (0.5%) | ||
| General physical health deterioration | 0/276 (0%) | 1/426 (0.2%) | ||
| Sudden death | 1/276 (0.4%) | 0/426 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis | 0/276 (0%) | 1/426 (0.2%) | ||
| Cholecystitis acute | 1/276 (0.4%) | 0/426 (0%) | ||
| Cholelithiasis | 1/276 (0.4%) | 0/426 (0%) | ||
| Infections and infestations | ||||
| Pneumonia | 2/276 (0.7%) | 16/426 (3.8%) | ||
| Lower respiratory tract infection | 1/276 (0.4%) | 5/426 (1.2%) | ||
| Bronchitis | 0/276 (0%) | 1/426 (0.2%) | ||
| Septic shock | 1/276 (0.4%) | 4/426 (0.9%) | ||
| Sepsis | 0/276 (0%) | 3/426 (0.7%) | ||
| Urinary tract infection | 1/276 (0.4%) | 5/426 (1.2%) | ||
| Herpes zoster | 0/276 (0%) | 1/426 (0.2%) | ||
| Varicella | 0/276 (0%) | 1/426 (0.2%) | ||
| Bronchiolitis | 0/276 (0%) | 1/426 (0.2%) | ||
| Pneumonia viral | 0/276 (0%) | 1/426 (0.2%) | ||
| Rhinovirus infection | 0/276 (0%) | 1/426 (0.2%) | ||
| Upper respiratory tract infection | 0/276 (0%) | 1/426 (0.2%) | ||
| Abdominal wall abscess | 1/276 (0.4%) | 0/426 (0%) | ||
| Gastroenteritis | 1/276 (0.4%) | 0/426 (0%) | ||
| Infection | 1/276 (0.4%) | 0/426 (0%) | ||
| Influenza | 1/276 (0.4%) | 0/426 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Hip fracture | 0/276 (0%) | 3/426 (0.7%) | ||
| Femur fracture | 0/276 (0%) | 1/426 (0.2%) | ||
| Fibula fracture | 0/276 (0%) | 1/426 (0.2%) | ||
| Tibia fracture | 0/276 (0%) | 1/426 (0.2%) | ||
| Tendon injury | 0/276 (0%) | 1/426 (0.2%) | ||
| Road traffic accident | 0/276 (0%) | 1/426 (0.2%) | ||
| Fall | 1/276 (0.4%) | 0/426 (0%) | ||
| Perirenal haematoma | 0/276 (0%) | 1/426 (0.2%) | ||
| Rib fracture | 0/276 (0%) | 1/426 (0.2%) | ||
| Subdural haematoma | 1/276 (0.4%) | 0/426 (0%) | ||
| Pelvic fracture | 1/276 (0.4%) | 0/426 (0%) | ||
| Pubis fracture | 1/276 (0.4%) | 0/426 (0%) | ||
| Gastroenteritis radiation | 1/276 (0.4%) | 0/426 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/276 (0%) | 2/426 (0.5%) | ||
| Hypercalcaemia | 1/276 (0.4%) | 1/426 (0.2%) | ||
| Hyponatraemia | 0/276 (0%) | 1/426 (0.2%) | ||
| Hyperkalaemia | 1/276 (0.4%) | 0/426 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Pathological fracture | 2/276 (0.7%) | 3/426 (0.7%) | ||
| Musculoskeletal chest pain | 0/276 (0%) | 1/426 (0.2%) | ||
| Neck pain | 0/276 (0%) | 1/426 (0.2%) | ||
| Pain in extremity | 0/276 (0%) | 1/426 (0.2%) | ||
| Back pain | 1/276 (0.4%) | 0/426 (0%) | ||
| Spinal pain | 0/276 (0%) | 1/426 (0.2%) | ||
| Osteolysis | 1/276 (0.4%) | 1/426 (0.2%) | ||
| Trismus | 0/276 (0%) | 1/426 (0.2%) | ||
| Muscular weakness | 0/276 (0%) | 1/426 (0.2%) | ||
| Osteoarthritis | 1/276 (0.4%) | 1/426 (0.2%) | ||
| Arthralgia | 1/276 (0.4%) | 0/426 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Plasma cell myeloma | 2/276 (0.7%) | 4/426 (0.9%) | ||
| Plasmacytoma | 1/276 (0.4%) | 2/426 (0.5%) | ||
| Basal cell carcinoma | 4/276 (1.4%) | 3/426 (0.7%) | ||
| Carcinoma in situ of skin | 0/276 (0%) | 1/426 (0.2%) | ||
| Squamous cell carcinoma of skin | 1/276 (0.4%) | 0/426 (0%) | ||
| Malignant melanoma | 0/276 (0%) | 2/426 (0.5%) | ||
| Adenocarcinoma of colon | 1/276 (0.4%) | 1/426 (0.2%) | ||
| Non-small cell lung cancer | 0/276 (0%) | 1/426 (0.2%) | ||
| Oesophageal carcinoma | 0/276 (0%) | 1/426 (0.2%) | ||
| Bladder transitional cell carcinoma | 1/276 (0.4%) | 0/426 (0%) | ||
| Invasive ductal breast carcinoma | 1/276 (0.4%) | 0/426 (0%) | ||
| Prostate cancer | 1/276 (0.4%) | 0/426 (0%) | ||
| Transitional cell cancer of the renal pelvis and ureter | 1/276 (0.4%) | 0/426 (0%) | ||
| Nervous system disorders | ||||
| Cerebral haemorrhage | 1/276 (0.4%) | 1/426 (0.2%) | ||
| Cerebral infarction | 0/276 (0%) | 1/426 (0.2%) | ||
| Ischaemic stroke | 0/276 (0%) | 1/426 (0.2%) | ||
| Transient ischaemic attack | 1/276 (0.4%) | 2/426 (0.5%) | ||
| Monoparesis | 0/276 (0%) | 1/426 (0.2%) | ||
| Partial seizures | 0/276 (0%) | 1/426 (0.2%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/276 (0%) | 5/426 (1.2%) | ||
| Chronic kidney disease | 0/276 (0%) | 1/426 (0.2%) | ||
| Urinary retention | 0/276 (0%) | 1/426 (0.2%) | ||
| Proteinuria | 0/276 (0%) | 1/426 (0.2%) | ||
| Haematuria | 1/276 (0.4%) | 0/426 (0%) | ||
| Reproductive system and breast disorders | ||||
| Postmenopausal haemorrhage | 0/276 (0%) | 1/426 (0.2%) | ||
| Endometrial hyperplasia | 1/276 (0.4%) | 0/426 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic obstructive pulmonary disease | 0/276 (0%) | 2/426 (0.5%) | ||
| Paraneoplastic pleural effusion | 0/276 (0%) | 1/426 (0.2%) | ||
| Pleural effusion | 0/276 (0%) | 1/426 (0.2%) | ||
| Pulmonary embolism | 0/276 (0%) | 2/426 (0.5%) | ||
| Hypoxia | 0/276 (0%) | 1/426 (0.2%) | ||
| Pneumonitis | 1/276 (0.4%) | 1/426 (0.2%) | ||
| Acute pulmonary oedema | 0/276 (0%) | 1/426 (0.2%) | ||
| Respiratory failure | 1/276 (0.4%) | 1/426 (0.2%) | ||
| Dyspnoea | 2/276 (0.7%) | 0/426 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Angioedema | 0/276 (0%) | 1/426 (0.2%) | ||
| Rash maculo-papular | 0/276 (0%) | 1/426 (0.2%) | ||
| Vascular disorders | ||||
| Hypertensive emergency | 0/276 (0%) | 1/426 (0.2%) | ||
| Jugular vein thrombosis | 0/276 (0%) | 1/426 (0.2%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Ixazomib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 182/276 (65.9%) | 340/426 (79.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 19/276 (6.9%) | 31/426 (7.3%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 22/276 (8%) | 114/426 (26.8%) | ||
| Diarrhoea | 34/276 (12.3%) | 99/426 (23.2%) | ||
| Vomiting | 10/276 (3.6%) | 101/426 (23.7%) | ||
| Constipation | 21/276 (7.6%) | 33/426 (7.7%) | ||
| Dyspepsia | 6/276 (2.2%) | 23/426 (5.4%) | ||
| General disorders | ||||
| Fatigue | 28/276 (10.1%) | 46/426 (10.8%) | ||
| Pyrexia | 13/276 (4.7%) | 46/426 (10.8%) | ||
| Oedema peripheral | 16/276 (5.8%) | 35/426 (8.2%) | ||
| Asthenia | 16/276 (5.8%) | 24/426 (5.6%) | ||
| Infections and infestations | ||||
| Upper respiratory tract infection | 30/276 (10.9%) | 66/426 (15.5%) | ||
| Nasopharyngitis | 18/276 (6.5%) | 35/426 (8.2%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 13/276 (4.7%) | 35/426 (8.2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 31/276 (11.2%) | 61/426 (14.3%) | ||
| Arthralgia | 19/276 (6.9%) | 49/426 (11.5%) | ||
| Musculoskeletal pain | 16/276 (5.8%) | 21/426 (4.9%) | ||
| Pain in extremity | 13/276 (4.7%) | 24/426 (5.6%) | ||
| Nervous system disorders | ||||
| Peripheral sensory neuropathy | 24/276 (8.7%) | 64/426 (15%) | ||
| Dizziness | 16/276 (5.8%) | 25/426 (5.9%) | ||
| Headache | 11/276 (4%) | 23/426 (5.4%) | ||
| Psychiatric disorders | ||||
| Insomnia | 12/276 (4.3%) | 26/426 (6.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 17/276 (6.2%) | 30/426 (7%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash maculo-papular | 2/276 (0.7%) | 34/426 (8%) | ||
| Vascular disorders | ||||
| Hypertension | 14/276 (5.1%) | 25/426 (5.9%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Takeda |
| Phone | +1-877-825-3327 |
| trialdisclosures@takeda.com |
- C16021
- U1111-1160-1702
- 2014-001394-13
- REec-2015-1414
- JapicCTI-152873
- 153300410A0048
- 1046003327
- SNCTP000001745
- 15/NE/0167
- 182602
- MOH_2017-06-15_000529