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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02312258
Recruitment Status : Active, not recruiting
First Posted : December 9, 2014
Results First Posted : November 10, 2020
Last Update Posted : November 10, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: Placebo
Drug: Ixazomib
Enrollment 706
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 Details 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
Hide 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 (Up to 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 (Up to data cut-off 12 August 2019).
Period Title: Overall Study
Started 281 425
Completed 30 66
Not Completed 251 359
Reason Not Completed
Adverse Event             15             47
Lost to Follow-up             0             1
Progressive Disease             174             188
Withdrawal by Subject             8             9
Reason not Specified             11             31
Participants Ongoing Treatment             43             83
Arm/Group Title Placebo Ixazomib Total
Hide 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 (Up to 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 (Up to data cut-off 12 August 2019). Total of all reporting groups
Overall Number of Baseline Participants 281 425 706
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all participants who were randomized and had post-randomization data.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 281 participants 425 participants 706 participants
72.8  (6.77) 72.3  (6.87) 72.5  (6.83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 281 participants 425 participants 706 participants
Female
126
  44.8%
203
  47.8%
329
  46.6%
Male
155
  55.2%
222
  52.2%
377
  53.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 281 participants 425 participants 706 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
   3.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 281 participants 425 participants 706 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
   0.0%
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
   2.0%
Not Reported
4
   1.4%
6
   1.4%
10
   1.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 281 participants 425 participants 706 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
   4.0%
32
   4.5%
Singapore
4
   1.4%
8
   1.9%
12
   1.7%
Korea, Republic Of
10
   3.6%
17
   4.0%
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
   0.0%
1
   0.2%
1
   0.1%
Czech Republic
31
  11.0%
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
  16.0%
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
   8.0%
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
   1.0%
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
   1.0%
Mexico
2
   0.7%
4
   0.9%
6
   0.8%
United States
3
   1.1%
6
   1.4%
9
   1.3%
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide 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: serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved FLC levels increase >10 mg/dl or bone marrow plasma cell ≥10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia.
Time Frame From the randomization until progressive disease (PD) or death or data cut-off date (12 Aug 2019) (Up to approximately 42 months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized and had post-randomization data.
Arm/Group Title Placebo Ixazomib
Hide 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 (Up to 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 (Up to data cut-off 12 August 2019).
Overall Number of Participants Analyzed 281 425
Median (95% Confidence Interval)
Unit of Measure: months
9.4
(8.51 to 11.47)
17.4
(14.78 to 20.30)
2.Secondary Outcome
Title Overall Survival (OS)
Hide 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 Not Reported
3.Secondary Outcome
Title Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period
Hide 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 Not Reported
4.Secondary Outcome
Title Time to Progression (TTP)
Hide 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 Not Reported
5.Secondary Outcome
Title Progression Free Survival 2 (PFS2)
Hide 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 Not Reported
6.Secondary Outcome
Title Time to Next Line Therapy (TTNT)
Hide 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 Not Reported
7.Secondary Outcome
Title Time to End of the Next-line of Therapy After Study Treatment
Hide 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 Not Reported
8.Secondary Outcome
Title Duration of Next-line Therapy
Hide 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 Not Reported
9.Secondary Outcome
Title Percentage of Participants Who Develop A New Primary Malignancy
Hide Description [Not Specified]
Time Frame From the randomization date till death or termination of the study (Up to approximately 76 to 104 months)
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Percentage of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative, or the Maintenance of MRD Negativity
Hide 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 Not Reported
11.Secondary Outcome
Title Correlation of MRD Status With PFS and OS
Hide 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 Not Reported
12.Secondary Outcome
Title OS in a High-risk Population
Hide 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 Not Reported
13.Secondary Outcome
Title PFS in a High-risk Population
Hide 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 Not Reported
14.Secondary Outcome
Title Eastern Cooperative Oncology Group (ECOG) Performance Status
Hide 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 Not Reported
15.Secondary Outcome
Title Percentage of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)
Hide Description A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution 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 medically significant. AEs are defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug.
Time Frame First dose of study drug through 30 days after last dose of study drug (Up to 25 months)
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Hide 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 Not Reported
17.Secondary Outcome
Title Number of Participants With Any Markedly Abnormal Standard Safety Laboratory Values
Hide 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 Not Reported
18.Secondary Outcome
Title Correlation Between Frailty Status and PFS and OS
Hide 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 Not Reported
19.Secondary Outcome
Title Pharmacokinetic Parameter: Plasma Concentration of Ixazomib
Hide 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 Not Reported
20.Secondary Outcome
Title Time to Resolution of Peripheral Neuropathy (PN) Events
Hide 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 Not Reported
21.Secondary Outcome
Title Time to Improvement of PN Events
Hide 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 Not Reported
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
Hide 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 (Up to 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 (Up to data cut-off 12 August 2019).
All-Cause Mortality
Placebo Ixazomib
Affected / at Risk (%) Affected / at Risk (%)
Total   6/276 (2.17%)   11/426 (2.58%) 
Hide Serious Adverse Events
Placebo Ixazomib
Affected / at Risk (%) Affected / at Risk (%)
Total   46/276 (16.67%)   94/426 (22.07%) 
Blood and lymphatic system disorders     
Pancytopenia  1  0/276 (0.00%)  1/426 (0.23%) 
Febrile neutropenia  1  0/276 (0.00%)  1/426 (0.23%) 
Anaemia  1  3/276 (1.09%)  0/426 (0.00%) 
Cardiac disorders     
Pericardial effusion  1  0/276 (0.00%)  2/426 (0.47%) 
Coronary artery disease  1  1/276 (0.36%)  1/426 (0.23%) 
Cardiac failure  1  0/276 (0.00%)  1/426 (0.23%) 
Cardiac failure acute  1  1/276 (0.36%)  0/426 (0.00%) 
Acute myocardial infarction  1  0/276 (0.00%)  1/426 (0.23%) 
Myocardial infarction  1  2/276 (0.72%)  0/426 (0.00%) 
Left ventricular dysfunction  1  0/276 (0.00%)  1/426 (0.23%) 
Atrial tachycardia  1  0/276 (0.00%)  1/426 (0.23%) 
Atrial flutter  1  1/276 (0.36%)  0/426 (0.00%) 
Cardiac arrest  1  0/276 (0.00%)  1/426 (0.23%) 
Bradycardia  1  1/276 (0.36%)  0/426 (0.00%) 
Eye disorders     
Cataract  1  0/276 (0.00%)  1/426 (0.23%) 
Uveitis  1  1/276 (0.36%)  0/426 (0.00%) 
Gastrointestinal disorders     
Inguinal hernia  1  0/276 (0.00%)  3/426 (0.70%) 
Vomiting  1  2/276 (0.72%)  3/426 (0.70%) 
Diarrhoea  1  0/276 (0.00%)  2/426 (0.47%) 
Abdominal pain  1  0/276 (0.00%)  2/426 (0.47%) 
Abdominal pain upper  1  0/276 (0.00%)  1/426 (0.23%) 
Gastrointestinal haemorrhage  1  0/276 (0.00%)  1/426 (0.23%) 
Melaena  1  0/276 (0.00%)  1/426 (0.23%) 
Chilaiditi's syndrome  1  0/276 (0.00%)  1/426 (0.23%) 
Large intestine polyp  1  0/276 (0.00%)  1/426 (0.23%) 
Gastritis  1  0/276 (0.00%)  1/426 (0.23%) 
Gastric disorder  1  0/276 (0.00%)  1/426 (0.23%) 
Gastrointestinal motility disorder  1  0/276 (0.00%)  1/426 (0.23%) 
Intestinal haemorrhage  1  0/276 (0.00%)  1/426 (0.23%) 
Rectal prolapse  1  1/276 (0.36%)  0/426 (0.00%) 
Ascites  1  1/276 (0.36%)  0/426 (0.00%) 
General disorders     
Non-cardiac chest pain  1  0/276 (0.00%)  2/426 (0.47%) 
Chest pain  1  0/276 (0.00%)  1/426 (0.23%) 
Pyrexia  1  1/276 (0.36%)  2/426 (0.47%) 
General physical health deterioration  1  0/276 (0.00%)  1/426 (0.23%) 
Sudden death  1  1/276 (0.36%)  0/426 (0.00%) 
Hepatobiliary disorders     
Cholecystitis  1  0/276 (0.00%)  1/426 (0.23%) 
Cholecystitis acute  1  1/276 (0.36%)  0/426 (0.00%) 
Cholelithiasis  1  1/276 (0.36%)  0/426 (0.00%) 
Infections and infestations     
Pneumonia  1  2/276 (0.72%)  16/426 (3.76%) 
Lower respiratory tract infection  1  1/276 (0.36%)  5/426 (1.17%) 
Bronchitis  1  0/276 (0.00%)  1/426 (0.23%) 
Septic shock  1  1/276 (0.36%)  4/426 (0.94%) 
Sepsis  1  0/276 (0.00%)  3/426 (0.70%) 
Urinary tract infection  1  1/276 (0.36%)  5/426 (1.17%) 
Herpes zoster  1  0/276 (0.00%)  1/426 (0.23%) 
Varicella  1  0/276 (0.00%)  1/426 (0.23%) 
Bronchiolitis  1  0/276 (0.00%)  1/426 (0.23%) 
Pneumonia viral  1  0/276 (0.00%)  1/426 (0.23%) 
Rhinovirus infection  1  0/276 (0.00%)  1/426 (0.23%) 
Upper respiratory tract infection  1  0/276 (0.00%)  1/426 (0.23%) 
Abdominal wall abscess  1  1/276 (0.36%)  0/426 (0.00%) 
Gastroenteritis  1  1/276 (0.36%)  0/426 (0.00%) 
Infection  1  1/276 (0.36%)  0/426 (0.00%) 
Influenza  1  1/276 (0.36%)  0/426 (0.00%) 
Injury, poisoning and procedural complications     
Hip fracture  1  0/276 (0.00%)  3/426 (0.70%) 
Femur fracture  1  0/276 (0.00%)  1/426 (0.23%) 
Fibula fracture  1  0/276 (0.00%)  1/426 (0.23%) 
Tibia fracture  1  0/276 (0.00%)  1/426 (0.23%) 
Tendon injury  1  0/276 (0.00%)  1/426 (0.23%) 
Road traffic accident  1  0/276 (0.00%)  1/426 (0.23%) 
Fall  1  1/276 (0.36%)  0/426 (0.00%) 
Perirenal haematoma  1  0/276 (0.00%)  1/426 (0.23%) 
Rib fracture  1  0/276 (0.00%)  1/426 (0.23%) 
Subdural haematoma  1  1/276 (0.36%)  0/426 (0.00%) 
Pelvic fracture  1  1/276 (0.36%)  0/426 (0.00%) 
Pubis fracture  1  1/276 (0.36%)  0/426 (0.00%) 
Gastroenteritis radiation  1  1/276 (0.36%)  0/426 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  0/276 (0.00%)  2/426 (0.47%) 
Hypercalcaemia  1  1/276 (0.36%)  1/426 (0.23%) 
Hyponatraemia  1  0/276 (0.00%)  1/426 (0.23%) 
Hyperkalaemia  1  1/276 (0.36%)  0/426 (0.00%) 
Musculoskeletal and connective tissue disorders     
Pathological fracture  1  2/276 (0.72%)  3/426 (0.70%) 
Musculoskeletal chest pain  1  0/276 (0.00%)  1/426 (0.23%) 
Neck pain  1  0/276 (0.00%)  1/426 (0.23%) 
Pain in extremity  1  0/276 (0.00%)  1/426 (0.23%) 
Back pain  1  1/276 (0.36%)  0/426 (0.00%) 
Spinal pain  1  0/276 (0.00%)  1/426 (0.23%) 
Osteolysis  1  1/276 (0.36%)  1/426 (0.23%) 
Trismus  1  0/276 (0.00%)  1/426 (0.23%) 
Muscular weakness  1  0/276 (0.00%)  1/426 (0.23%) 
Osteoarthritis  1  1/276 (0.36%)  1/426 (0.23%) 
Arthralgia  1  1/276 (0.36%)  0/426 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Plasma cell myeloma  1  2/276 (0.72%)  4/426 (0.94%) 
Plasmacytoma  1  1/276 (0.36%)  2/426 (0.47%) 
Basal cell carcinoma  1  4/276 (1.45%)  3/426 (0.70%) 
Carcinoma in situ of skin  1  0/276 (0.00%)  1/426 (0.23%) 
Squamous cell carcinoma of skin  1  1/276 (0.36%)  0/426 (0.00%) 
Malignant melanoma  1  0/276 (0.00%)  2/426 (0.47%) 
Adenocarcinoma of colon  1  1/276 (0.36%)  1/426 (0.23%) 
Non-small cell lung cancer  1  0/276 (0.00%)  1/426 (0.23%) 
Oesophageal carcinoma  1  0/276 (0.00%)  1/426 (0.23%) 
Bladder transitional cell carcinoma  1  1/276 (0.36%)  0/426 (0.00%) 
Invasive ductal breast carcinoma  1  1/276 (0.36%)  0/426 (0.00%) 
Prostate cancer  1  1/276 (0.36%)  0/426 (0.00%) 
Transitional cell cancer of the renal pelvis and ureter  1  1/276 (0.36%)  0/426 (0.00%) 
Nervous system disorders     
Cerebral haemorrhage  1  1/276 (0.36%)  1/426 (0.23%) 
Cerebral infarction  1  0/276 (0.00%)  1/426 (0.23%) 
Ischaemic stroke  1  0/276 (0.00%)  1/426 (0.23%) 
Transient ischaemic attack  1  1/276 (0.36%)  2/426 (0.47%) 
Monoparesis  1  0/276 (0.00%)  1/426 (0.23%) 
Partial seizures  1  0/276 (0.00%)  1/426 (0.23%) 
Renal and urinary disorders     
Acute kidney injury  1  0/276 (0.00%)  5/426 (1.17%) 
Chronic kidney disease  1  0/276 (0.00%)  1/426 (0.23%) 
Urinary retention  1  0/276 (0.00%)  1/426 (0.23%) 
Proteinuria  1  0/276 (0.00%)  1/426 (0.23%) 
Haematuria  1  1/276 (0.36%)  0/426 (0.00%) 
Reproductive system and breast disorders     
Postmenopausal haemorrhage  1  0/276 (0.00%)  1/426 (0.23%) 
Endometrial hyperplasia  1  1/276 (0.36%)  0/426 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/276 (0.00%)  2/426 (0.47%) 
Paraneoplastic pleural effusion  1  0/276 (0.00%)  1/426 (0.23%) 
Pleural effusion  1  0/276 (0.00%)  1/426 (0.23%) 
Pulmonary embolism  1  0/276 (0.00%)  2/426 (0.47%) 
Hypoxia  1  0/276 (0.00%)  1/426 (0.23%) 
Pneumonitis  1  1/276 (0.36%)  1/426 (0.23%) 
Acute pulmonary oedema  1  0/276 (0.00%)  1/426 (0.23%) 
Respiratory failure  1  1/276 (0.36%)  1/426 (0.23%) 
Dyspnoea  1  2/276 (0.72%)  0/426 (0.00%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  0/276 (0.00%)  1/426 (0.23%) 
Rash maculo-papular  1  0/276 (0.00%)  1/426 (0.23%) 
Vascular disorders     
Hypertensive emergency  1  0/276 (0.00%)  1/426 (0.23%) 
Jugular vein thrombosis  1  0/276 (0.00%)  1/426 (0.23%) 
1
Term from vocabulary, MedDRA:22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Ixazomib
Affected / at Risk (%) Affected / at Risk (%)
Total   182/276 (65.94%)   340/426 (79.81%) 
Blood and lymphatic system disorders     
Anaemia  1  19/276 (6.88%)  31/426 (7.28%) 
Gastrointestinal disorders     
Nausea  1  22/276 (7.97%)  114/426 (26.76%) 
Diarrhoea  1  34/276 (12.32%)  99/426 (23.24%) 
Vomiting  1  10/276 (3.62%)  101/426 (23.71%) 
Constipation  1  21/276 (7.61%)  33/426 (7.75%) 
Dyspepsia  1  6/276 (2.17%)  23/426 (5.40%) 
General disorders     
Fatigue  1  28/276 (10.14%)  46/426 (10.80%) 
Pyrexia  1  13/276 (4.71%)  46/426 (10.80%) 
Oedema peripheral  1  16/276 (5.80%)  35/426 (8.22%) 
Asthenia  1  16/276 (5.80%)  24/426 (5.63%) 
Infections and infestations     
Upper respiratory tract infection  1  30/276 (10.87%)  66/426 (15.49%) 
Nasopharyngitis  1  18/276 (6.52%)  35/426 (8.22%) 
Metabolism and nutrition disorders     
Decreased appetite  1  13/276 (4.71%)  35/426 (8.22%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  31/276 (11.23%)  61/426 (14.32%) 
Arthralgia  1  19/276 (6.88%)  49/426 (11.50%) 
Musculoskeletal pain  1  16/276 (5.80%)  21/426 (4.93%) 
Pain in extremity  1  13/276 (4.71%)  24/426 (5.63%) 
Nervous system disorders     
Peripheral sensory neuropathy  1  24/276 (8.70%)  64/426 (15.02%) 
Dizziness  1  16/276 (5.80%)  25/426 (5.87%) 
Headache  1  11/276 (3.99%)  23/426 (5.40%) 
Psychiatric disorders     
Insomnia  1  12/276 (4.35%)  26/426 (6.10%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  17/276 (6.16%)  30/426 (7.04%) 
Skin and subcutaneous tissue disorders     
Rash maculo-papular  1  2/276 (0.72%)  34/426 (7.98%) 
Vascular disorders     
Hypertension  1  14/276 (5.07%)  25/426 (5.87%) 
1
Term from vocabulary, MedDRA:22.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT02312258    
Other Study ID Numbers: C16021
U1111-1160-1702 ( Registry Identifier: WHO )
2014-001394-13 ( EudraCT Number )
REec-2015-1414 ( Registry Identifier: REec )
JapicCTI-152873 ( Registry Identifier: JapicCTI )
153300410A0048 ( Registry Identifier: RNEC )
1046003327 ( Registry Identifier: TCTIN )
SNCTP000001745 ( Registry Identifier: SNCTP )
15/NE/0167 ( Registry Identifier: NRES )
182602 ( Registry Identifier: HC-CTD )
MOH_2017-06-15_000529 ( Other Identifier: CRS )
First Submitted: December 5, 2014
First Posted: December 9, 2014
Results First Submitted: August 6, 2020
Results First Posted: November 10, 2020
Last Update Posted: November 10, 2020