Multiple Myeloma
Conditions
Keywords
Newly Diagnosed multiple myeloma, multiple myeloma, MLN9708, IXAZOMIB, Proteasome inhibitor, Tourmaline MM2
Brief summary
The purpose of this study is to provide continued access to ixazomib and/or lenalidomide to participants who are continuing to have clinical benefit and to continue collecting relevant safety data to monitor safety in participants with Newly Diagnosed Multiple Myeloma (NDMM) who are not eligible for stem cell transplant.
Interventions
DRUGIxazomib
IXAZOMIB capsules.
DRUGPlacebo
IXAZOMIB matching-placebo capsules.
DRUGDexamethasone
Dexamethasone tablets.
DRUGLenalidomide
Lenalidomide capsules.
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female participants 18 years or older diagnosed with Multiple Myeloma according to standard criteria who have not received prior treatment for multiple myeloma. 2. Participants for whom lenalidomide and dexamethasone treatment is appropriate and who are not eligible for high-dose therapy followed by stem-cell transplantation (HDT-SCT) for 1 or more of the following reasons: * The participant is 65 years of age or older. * The participant is less than 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT. 3. Measurable disease as specified in study protocol. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 5. Meet the clinical laboratories criteria as specified in the protocol. 6. Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence, and must also agree to ongoing pregnancy testing; must also adhere to the guidelines of the lenalidomide pregnancy prevention program. 7. Male participants who agree to practice effective barrier contraception or agree to practice true abstinence AND must adhere to the guidelines of the lenalidomide pregnancy prevention program. 8. Suitable venous access for the study-required blood sampling. 9. Must be able to take concurrent aspirin 70 mg to 325 mg daily (or enoxaparin if aspirin allergic). 10. Voluntary written consent. 11. Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
Exclusion criteria
1. Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen. 2. Diagnosed and treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 3. Inability or unwillingness to receive antithrombotic therapy. 4. Female participants who are lactating or pregnant. 5. Major surgery or radiotherapy within 14 days before randomization. 6. Infection requiring intravenous antibiotics within 14 days before the first dose of study drug. 7. Central nervous system involvement. 8. Diagnosis of Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome. 9. Evidence of current uncontrolled cardiovascular conditions within 6 months prior to randomization, including: Uncontrolled hypertension, cardiac arrhythmias, or congestive heart failure; Unstable angina, or Myocardial infarction. 10. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin,itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before randomization in the study. 11. Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. 12. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (e.g., peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause). 13. Psychiatric illness/social situation that would limit compliance with study requirements. 14. Known allergy to any of the study medications. 15. 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. 16. Treatment with any investigational products within 60 days before randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to approximately 79 months | PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause according to International Myeloma Working Group (IMWG) criteria whichever occurs first. PD required one of the following: Increase of \>=25% from nadir in: Serum M-component and/or (the absolute increase must be \>=0.5 g/dL); Urine M-component and/or (the absolute increase must be \>=200 mg/24 hours); in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be \> 10 mg/dL); Bone marrow plasma cell percentage: the absolute % must be \>10%; development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; hypercalcemia (corrected serum calcium \> 11.5 mg/dL or 2.85 mmol/L). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate | Up to approximately 9 years | CR rate was defined as the percentage of participants who achieve CR assessed by an IRC relative to the intent-to-treat (ITT) population during the treatment period. Percentage of participants with CR, as assessed by IMWG disease assessment criteria were reported. CR was defined as negative immunofixation of serum and urine along with the disappearance of any soft tissue plasmacytomas and \<5 % plasma cells (PC's) in bone marrow. |
| Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use | Up to approximately 9 years | Pain response rate was defined as percentage of participants with pain response. Pain response was defined as the occurrence of at least a 30% reduction from baseline in BPI-SF worst pain score over the last 24 hours without an increase in analgesic use for 2 consecutive measurements \> 28 days apart, were reported. Brief Pain Inventory - Short Form (m-BPI-SF) is a participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable). Percentages are rounded off to the nearest single decimal. |
| Overall Response Rate (ORR) | Up to approximately 9 years | ORR was defined as the percentage of participants who achieved CR + partial response (PR) + very good partial response (VGPR) (including sCR) or better relative to the ITT population during treatment period. CR was defined as negative immunofixation of serum and urine along with the disappearance of any soft tissue plasmacytomas and \<5 % PC's in bone marrow. PR was defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% along with ≥50% reduction in the size of soft tissue plasmacytomas. VGPR was defined as ≥90% in serum M-component plus urine M-component \<100 mg/24. sCR is defined as stringent complete response. Percentages are rounded off to nearest whole numbers. |
| Time to Response | Up to approximately 9 years | Time to response was defined as the time from the date of randomization to the first documentation of PR or better, as measured by IMWG criteria. |
| Duration of Response | Up to approximately 9 years | Duration of response was measured as the time from the date of first documentation of PR or better to the date of first documented progression (PD) for responders, as measured by IMWG criteria. |
| Time to Progression (TTP) | Up to approximately 9 years | Time to progression was defined as the time from randomization to the date of first documented disease progression. |
| Progression Free Survival (PFS)-2 | Up to approximately 9 years | PFS2 was defined as the time from the date of randomization to the date of documentation of disease progression on the subsequent line of anticancer therapy, as assessed by the investigator in accordance with IMWG criteria, or death due to any cause, whichever occurs first. |
| Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Up to approximately 9 years | Eastern Cooperative Oncology Group (ECOG) scale score ranged from 0 to 5, where 0 indicated normal activity and 5 indicated death. The data is reported for those categories where at least 1 participant had worst post-baseline value for each ECOG score. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years) | An AE was any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. |
| Overall Survival (OS) | From the date of randomization to death due to any cause (Up to approximately 9 years) | OS was defined as the time from the date of randomization to the date of death. Participants without documented death at the time of analysis are censored at the date last known to be alive. |
| Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Baseline to approximately 9 years | EORTC-QLQ-C30 scale was used to assess HRQOL in cancer participants and contains 30 items. Subscale with individual items include physical functioning items 1-5, role functioning items 6-7, emotional functioning items 21-24, cognitive functioning items 20, 25, social functioning items 26-27, quality of life items 29-30, fatigue items 10, 12, 18, nausea and vomiting items 14-15, pain items 9, 19, dyspnoea item 8, insomnia item 11, appetite loss item 13, constipation item 16, diarrhoea item 17, financial difficulties item 28. Raw scores were converted into scale scores ranging from 0 to 100. For the functional scales and the global health status scale, higher scores represent better HRQOL; whereas for the symptom scales lower scores represent better HRQOL. Positive change in functional and global health status scale indicated improvement; negative change for the symptom scales indicates improvement. |
| Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Baseline to approximately 9 years | EORTC QLQ-MY20 was a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. The scale has 20 questions. Subscale and individual items include future perspective items 18-20, body image item 17, disease symptoms items 1-6, side effects of treatment items 7-16. Raw scores are averaged, and transformed to 0-100 scale, where higher score is better quality of life. Positive change indicates improvement. |
| OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations | From the date of randomization to death due to any cause (Up to approximately 9 years) | OS was defined as the time from the date of randomization to the date of death, as assessed in high-risk population carrying del(17p), t(4;14), or t(14;16) mutations. High risk category includes t(4;14), t(14;16), or del(17) abnormalities. |
| PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations | Up to approximately 9 years | PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease based on central laboratory results and IMWG criteria as evaluated by an independent review committee (IRC) or death due to any cause, whichever occurs first, as assessed in high-risk population carrying del(17p), t(4;14), or t(14;16) mutations. |
| Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry | Up to Cycle 18 (cycle length = 28 days) | The absence of minimal residual disease (MRD negativity) was tested in all participants who achieve a CR and maintained it until Cycle 18, using bone marrow aspirates. |
| Time to Pain Progression | Up to approximately 9 years | Time to pain progression was assessed as the time from randomization to the date of initial progression classification. Pain progression was defined as the occurrence of 1 of the following and confirmed by 2 consecutive evaluations (To qualify as progression, the participant must have a BPI-SF worst pain score \> 4 during pain progression): 1) a ≥ 2 point and 30% increase from Baseline in BPI-SF worst pain score without an increase in analgesic use, or 2) a 25% or more increase in analgesic use from Baseline without a decrease in BPI-SF worst pain score from Baseline. Brief Pain Inventory - Short Form (m-BPI-SF) is a participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable). |
| Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 1 Day 1: Post-dose at multiple timepoints up to 4 hours; Pre-dose at Cycle 1 Day 14, Cycles 2-3 Day 1 and Day 14, Cycles 4-11 Day 1 (Each cycle length = 28 days) | — |
| Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs) | From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years) | SRE is defined as new fractures \[including vertebral compression fractures\], irradiation of or surgery on bone, or spinal cord compression. |
| Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years) | The laboratory values assessment included serum chemistry and hematology. The Serum chemistry assessment included blood urea nitrogen (BUN), creatinine, bilirubin (total), urate, lactate dehydrogenase, phosphate, albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, sodium, potassium, calcium, chloride, carbon dioxide (CO2), magnesium, thyroid stimulating hormone (TSH). Hematology assessment included hemoglobin, hematocrit, platelet (count), leukocytes with differential neutrophils (ANC). Participants with abnormal serum chemistry laboratory values reported as TEAEs are reported. TEAEs were defined as events that occurred after administration of the first dose of any agent in the study drug regimen and through 30 days after the last dose of any agent in the study drug regimen. |
Countries
Belgium, Canada, France, New Zealand, Russia, South Korea, United States
Participant flow
Recruitment details
Participants took part in the study at 238 investigative sites in multiple countries from 29 April 2013 to 24 June 2022.
Pre-assignment details
Participants with newly diagnosed multiple myeloma were enrolled in 1:1 ratio to receive ixazomib or placebo in addition to the background therapy of Lenalidomide and Dexamethasone (LenDex) in this study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + LenDex Participants who were randomly assigned to receive placebo matching capsule single oral dose on Days 1, 8 and 15 along with standard regimen of LenDex (lenalidomide 25 mg capsules orally on Days 1-21 and dexamethasone 40 mg tablets orally on Days 1, 8, 15 and 22) for the first 18 cycles (each cycle was of 28 days). Following Cycle 18, participants received 3.0 mg ixazomib matching placebo capsule as single oral dose on Days 1, 8 and 15 along with lenalidomide 10 mg capsules orally on Days 1-21 in each 28-day cycle until progressive disease or unacceptable toxicity, whichever comes first up to end of study (up to approximately 109 months). | 354 |
| Ixazomib + LenDex Participants who were randomly assigned to receive Ixazomib 4.0 mg capsule single oral dose on Days 1, 8 and 15 along with standard regimen of LenDex (lenalidomide 25 mg capsules orally on Days 1-21 and dexamethasone 40 mg tablets orally on Days 1, 8, 15 and 22) for the first 18 cycles (each cycle was of 28 days). Following Cycle 18, participants received 3.0 mg ixazomib capsule as single oral dose on Days 1, 8 and 15 along with lenalidomide 10 mg capsules orally on Days 1-21 in each 28-day cycle until progressive disease or unacceptable toxicity, whichever comes first up to end of study (up to approximately 109 months). | 351 |
| Total | 705 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 10 |
| Overall Study | Reason not Specified | 142 | 141 |
| Overall Study | Withdrawal by Subject | 24 | 22 |
Baseline characteristics
| Characteristic | Placebo + LenDex | Ixazomib + LenDex | Total |
|---|---|---|---|
| Age, Continuous | 73.7 years STANDARD_DEVIATION 5.91 | 73.5 years STANDARD_DEVIATION 6.53 | 73.6 years STANDARD_DEVIATION 6.22 |
| Body Surface Area (BSA) | 1.789 m^2 STANDARD_DEVIATION 0.2306 | 1.810 m^2 STANDARD_DEVIATION 0.2456 | 1.800 m^2 STANDARD_DEVIATION 0.2383 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 12 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 340 Participants | 337 Participants | 677 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Height | 164.7 cm STANDARD_DEVIATION 10.04 | 164.3 cm STANDARD_DEVIATION 10.13 | 164.5 cm STANDARD_DEVIATION 10.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 52 Participants | 44 Participants | 96 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 11 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 285 Participants | 291 Participants | 576 Participants |
| Region of Enrollment Belgium | 37 Participants | 36 Participants | 73 Participants |
| Region of Enrollment Canada | 59 Participants | 63 Participants | 122 Participants |
| Region of Enrollment France | 136 Participants | 126 Participants | 262 Participants |
| Region of Enrollment Japan | 28 Participants | 31 Participants | 59 Participants |
| Region of Enrollment New Zealand | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment Russia | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment South Korea | 20 Participants | 11 Participants | 31 Participants |
| Region of Enrollment United States | 68 Participants | 79 Participants | 147 Participants |
| Sex: Female, Male Female | 172 Participants | 179 Participants | 351 Participants |
| Sex: Female, Male Male | 182 Participants | 172 Participants | 354 Participants |
| Weight | 70.53 kg STANDARD_DEVIATION 15.353 | 72.67 kg STANDARD_DEVIATION 16.995 | 71.59 kg STANDARD_DEVIATION 16.215 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 107 / 160 | 95 / 163 | 63 / 189 | 63 / 191 |
| other Total, other adverse events | 159 / 160 | 162 / 163 | 189 / 189 | 191 / 191 |
| serious Total, serious adverse events | 105 / 160 | 119 / 163 | 119 / 189 | 125 / 191 |
Outcome results
Primary
Progression Free Survival (PFS)
PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause according to International Myeloma Working Group (IMWG) criteria whichever occurs first. PD required one of the following: Increase of \>=25% from nadir in: Serum M-component and/or (the absolute increase must be \>=0.5 g/dL); Urine M-component and/or (the absolute increase must be \>=200 mg/24 hours); in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be \> 10 mg/dL); Bone marrow plasma cell percentage: the absolute % must be \>10%; development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; hypercalcemia (corrected serum calcium \> 11.5 mg/dL or 2.85 mmol/L).
Time frame: Up to approximately 79 months
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + LenDex | Progression Free Survival (PFS) | 21.8 months |
| Ixazomib + LenDex | Progression Free Survival (PFS) | 35.3 months |
p-value: 0.07395% CI: [0.676, 1.018]Log Rank
Secondary
Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score
EORTC-QLQ-C30 scale was used to assess HRQOL in cancer participants and contains 30 items. Subscale with individual items include physical functioning items 1-5, role functioning items 6-7, emotional functioning items 21-24, cognitive functioning items 20, 25, social functioning items 26-27, quality of life items 29-30, fatigue items 10, 12, 18, nausea and vomiting items 14-15, pain items 9, 19, dyspnoea item 8, insomnia item 11, appetite loss item 13, constipation item 16, diarrhoea item 17, financial difficulties item 28. Raw scores were converted into scale scores ranging from 0 to 100. For the functional scales and the global health status scale, higher scores represent better HRQOL; whereas for the symptom scales lower scores represent better HRQOL. Positive change in functional and global health status scale indicated improvement; negative change for the symptom scales indicates improvement.
Time frame: Baseline to approximately 9 years
Population: ITT population included all participants who were randomized. Overall number of participants analyzed is the number of participants available for analyses. Number analyzed indicates the number of participants available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Pain: End of Treatment | -5.5 score on a scale | Standard Deviation 33.77 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Cognitive Functioning: Baseline | 77.8 score on a scale | Standard Deviation 22.97 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Nausea and Vomiting: Baseline | 7.1 score on a scale | Standard Deviation 15.75 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Global Health Status/QoL: End of Treatment | -2.2 score on a scale | Standard Deviation 26.03 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Nausea and Vomiting: End of Treatment | -0.5 score on a scale | Standard Deviation 19.8 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Cognitive Functioning: End of Treatment | -3.2 score on a scale | Standard Deviation 25.14 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Dyspnoea: Baseline | 26.2 score on a scale | Standard Deviation 30.25 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Role Functioning: End of Treatment | -0.3 score on a scale | Standard Deviation 36.25 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Dyspnoea: End of Treatment | -3.6 score on a scale | Standard Deviation 30.86 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Social Functioning: Baseline | 69.1 score on a scale | Standard Deviation 32.54 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Insomnia: Baseline | 30.3 score on a scale | Standard Deviation 30.31 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Physical Functioning: End of Treatment | 1.7 score on a scale | Standard Deviation 26.81 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Insomnia: End of Treatment | -1.5 score on a scale | Standard Deviation 35.06 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Social Functioning: End of Treatment | -2.9 score on a scale | Standard Deviation 31.56 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Appetite Loss: Baseline | 25.4 score on a scale | Standard Deviation 33.14 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Emotional Functioning: Baseline | 73.5 score on a scale | Standard Deviation 23.09 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Appetite Loss: End of Treatment | -1.2 score on a scale | Standard Deviation 37.42 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Fatigue: Baseline | 44.6 score on a scale | Standard Deviation 28.3 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Constipation: Baseline | 25.9 score on a scale | Standard Deviation 32.94 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Physical Functioning: Baseline | 60.0 score on a scale | Standard Deviation 28.73 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Constipation: End of Treatment | -7.1 score on a scale | Standard Deviation 39.03 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Fatigue: End of Treatment | -2.3 score on a scale | Standard Deviation 27.75 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Diarrhoea: Baseline | 8.2 score on a scale | Standard Deviation 19.45 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Emotional Functioning: End of Treatment | -2.4 score on a scale | Standard Deviation 21.7 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Diarrhoea: End of Treatment | 10.7 score on a scale | Standard Deviation 27.72 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Pain: Baseline | 45.6 score on a scale | Standard Deviation 34.04 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Financial Difficulties: Baseline | 12.5 score on a scale | Standard Deviation 24.04 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Role Functioning: Baseline | 54.9 score on a scale | Standard Deviation 36.52 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Financial Difficulties: End of Treatment | 2.0 score on a scale | Standard Deviation 27.42 |
| Placebo + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Global Health Status/QoL: Baseline | 55.2 score on a scale | Standard Deviation 23.53 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Financial Difficulties: End of Treatment | 0.8 score on a scale | Standard Deviation 25.61 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Global Health Status/QoL: Baseline | 56.4 score on a scale | Standard Deviation 23.66 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Global Health Status/QoL: End of Treatment | -4.1 score on a scale | Standard Deviation 29.48 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Physical Functioning: Baseline | 61.4 score on a scale | Standard Deviation 27.96 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Physical Functioning: End of Treatment | 0.3 score on a scale | Standard Deviation 28.23 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Role Functioning: Baseline | 56.5 score on a scale | Standard Deviation 36.6 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Role Functioning: End of Treatment | -1.8 score on a scale | Standard Deviation 36.74 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Emotional Functioning: Baseline | 72.6 score on a scale | Standard Deviation 24.84 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Emotional Functioning: End of Treatment | -0.5 score on a scale | Standard Deviation 24.35 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Cognitive Functioning: Baseline | 78.3 score on a scale | Standard Deviation 25.92 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Cognitive Functioning: End of Treatment | -5.1 score on a scale | Standard Deviation 24.7 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Social Functioning: Baseline | 69.5 score on a scale | Standard Deviation 33.01 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Social Functioning: End of Treatment | -2.5 score on a scale | Standard Deviation 36.57 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Fatigue: Baseline | 40.8 score on a scale | Standard Deviation 27.69 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Fatigue: End of Treatment | 4.5 score on a scale | Standard Deviation 31.04 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Pain: Baseline | 42.5 score on a scale | Standard Deviation 33.51 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Pain: End of Treatment | -3.5 score on a scale | Standard Deviation 34.55 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Nausea and Vomiting: Baseline | 8.1 score on a scale | Standard Deviation 18.49 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Nausea and Vomiting: End of Treatment | 1.6 score on a scale | Standard Deviation 25.22 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Dyspnoea: Baseline | 24.0 score on a scale | Standard Deviation 29.35 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Dyspnoea: End of Treatment | 2.8 score on a scale | Standard Deviation 33.83 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Insomnia: Baseline | 34.3 score on a scale | Standard Deviation 32.2 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Insomnia: End of Treatment | -1.1 score on a scale | Standard Deviation 36.06 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Appetite Loss: Baseline | 25.5 score on a scale | Standard Deviation 33.04 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Appetite Loss: End of Treatment | 3.4 score on a scale | Standard Deviation 38.65 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Constipation: Baseline | 24.9 score on a scale | Standard Deviation 32.19 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Constipation: End of Treatment | -5.7 score on a scale | Standard Deviation 35.83 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Diarrhoea: Baseline | 6.7 score on a scale | Standard Deviation 16.58 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Diarrhoea: End of Treatment | 18.3 score on a scale | Standard Deviation 31.73 |
| Ixazomib + LenDex | Change From Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score | Financial Difficulties: Baseline | 12.3 score on a scale | Standard Deviation 24.03 |
Secondary
Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale
EORTC QLQ-MY20 was a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. The scale has 20 questions. Subscale and individual items include future perspective items 18-20, body image item 17, disease symptoms items 1-6, side effects of treatment items 7-16. Raw scores are averaged, and transformed to 0-100 scale, where higher score is better quality of life. Positive change indicates improvement.
Time frame: Baseline to approximately 9 years
Population: ITT population included all participants who were randomized. Overall number of participants analyzed is the number of participants available for analyses. Number analyzed indicates the number of participants available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Disease Symptoms: Baseline | 30.3 score on a scale | Standard Deviation 23.76 |
| Placebo + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Disease Symptoms: End of Treatment | -3.1 score on a scale | Standard Deviation 20.74 |
| Placebo + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Side-Effects: Baseline | 18.0 score on a scale | Standard Deviation 14.53 |
| Placebo + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Side-Effects: End of Treatment | 1.7 score on a scale | Standard Deviation 14.52 |
| Placebo + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Body Image: Baseline | 81.7 score on a scale | Standard Deviation 27.67 |
| Placebo + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Body Image: End of Treatment | -7.8 score on a scale | Standard Deviation 31.93 |
| Placebo + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Future Perspective: Baseline | 57.3 score on a scale | Standard Deviation 25.95 |
| Placebo + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Future Perspective: End of Treatment | 4.4 score on a scale | Standard Deviation 24.85 |
| Ixazomib + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Future Perspective: End of Treatment | 6.0 score on a scale | Standard Deviation 25.69 |
| Ixazomib + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Disease Symptoms: Baseline | 29.2 score on a scale | Standard Deviation 22.97 |
| Ixazomib + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Body Image: Baseline | 81.2 score on a scale | Standard Deviation 29.11 |
| Ixazomib + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Disease Symptoms: End of Treatment | -5.3 score on a scale | Standard Deviation 22.44 |
| Ixazomib + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Future Perspective: Baseline | 55.0 score on a scale | Standard Deviation 28.47 |
| Ixazomib + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Side-Effects: Baseline | 17.6 score on a scale | Standard Deviation 15.04 |
| Ixazomib + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Body Image: End of Treatment | -2.3 score on a scale | Standard Deviation 29.66 |
| Ixazomib + LenDex | Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale | Side-Effects: End of Treatment | 3.3 score on a scale | Standard Deviation 15.91 |
Secondary
Cmax: Maximum Plasma Concentration for Ixazomib
Time frame: Cycle 1 Day 1: Post-dose at multiple timepoints up to 4 hours; Pre-dose at Cycle 1 Day 14, Cycles 2-3 Day 1 and Day 14, Cycles 4-11 Day 1 (Each cycle length = 28 days)
Population: Pharmacokinetic (PK) analysis population is defined as subjects with at least one PK sample that was collected and analyzed. Overall number of participants analyzed is the number of participants available for analyses. Number analyzed indicates the number of participants available for analysis at the given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 7 Day 1: Pre-dose | 2.598 nanograms per milliliter | Standard Deviation 1.4658 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 1 Day 1: 1 Hour Post-dose | 44.745 nanograms per milliliter | Standard Deviation 35.9404 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 1 Day 1: 4 Hours Post-dose | 16.253 nanograms per milliliter | Standard Deviation 17.0407 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 1 Day 14: Pre-dose | 7.867 nanograms per milliliter | Standard Deviation 15.442 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 2 Day 1: Pre-dose | 2.664 nanograms per milliliter | Standard Deviation 2.277 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 2 Day 14: Pre-dose | 8.521 nanograms per milliliter | Standard Deviation 14.7411 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 3 Day 1: Pre-dose | 2.763 nanograms per milliliter | Standard Deviation 1.6318 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 3 Day 14: Pre-dose | 8.490 nanograms per milliliter | Standard Deviation 17.672 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 4 Day 1: Pre-dose | 3.284 nanograms per milliliter | Standard Deviation 6.1116 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 5 Day 1: Pre-dose | 3.594 nanograms per milliliter | Standard Deviation 13.2046 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 6 Day 1: Pre-dose | 2.603 nanograms per milliliter | Standard Deviation 1.5242 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 8 Day 1: Pre-dose | 2.539 nanograms per milliliter | Standard Deviation 1.5549 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 9 Day 1: Pre-dose | 2.593 nanograms per milliliter | Standard Deviation 2.0867 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 10 Day 1: Pre-dose | 2.536 nanograms per milliliter | Standard Deviation 1.7431 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 11 Day 1: Pre-dose | 2.667 nanograms per milliliter | Standard Deviation 4.5448 |
| Placebo + LenDex | Cmax: Maximum Plasma Concentration for Ixazomib | Cycle 12 Day 1: Pre-dose | 2.686 nanograms per milliliter | Standard Deviation 1.8949 |
Secondary
Complete Response (CR) Rate
CR rate was defined as the percentage of participants who achieve CR assessed by an IRC relative to the intent-to-treat (ITT) population during the treatment period. Percentage of participants with CR, as assessed by IMWG disease assessment criteria were reported. CR was defined as negative immunofixation of serum and urine along with the disappearance of any soft tissue plasmacytomas and \<5 % plasma cells (PC's) in bone marrow.
Time frame: Up to approximately 9 years
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + LenDex | Complete Response (CR) Rate | 14 percentage of participants |
| Ixazomib + LenDex | Complete Response (CR) Rate | 26 percentage of participants |
p-value: <0.00195% CI: [1.43, 3.09]Cochran-Mantel-Haenszel
Secondary
Duration of Response
Duration of response was measured as the time from the date of first documentation of PR or better to the date of first documented progression (PD) for responders, as measured by IMWG criteria.
Time frame: Up to approximately 9 years
Population: Response-evaluable population was defined as all participants in the ITT population who receive at least 1 dose of any study drug, have measurable disease at baseline, and at least 1 post baseline response assessment assessed by an IRC. Overall number of participants analyzed are the number of responders.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + LenDex | Duration of Response | 37.5 months |
| Ixazomib + LenDex | Duration of Response | 50.6 months |
Secondary
Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs)
The laboratory values assessment included serum chemistry and hematology. The Serum chemistry assessment included blood urea nitrogen (BUN), creatinine, bilirubin (total), urate, lactate dehydrogenase, phosphate, albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, sodium, potassium, calcium, chloride, carbon dioxide (CO2), magnesium, thyroid stimulating hormone (TSH). Hematology assessment included hemoglobin, hematocrit, platelet (count), leukocytes with differential neutrophils (ANC). Participants with abnormal serum chemistry laboratory values reported as TEAEs are reported. TEAEs were defined as events that occurred after administration of the first dose of any agent in the study drug regimen and through 30 days after the last dose of any agent in the study drug regimen.
Time frame: From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years)
Population: Safety population is defined as all participants who receive at least 1 dose of any study drug. Data for safety is summarized as per the duration of exposure to study treatment (exposure up to 18 cycles; exposure ≥19 cycles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Neutropenia | 36 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperglycaemia | 4 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Thrombocytopenia | 15 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | White blood cell count decreased | 5 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Leukopenia | 3 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypocalcaemia | 13 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperuricaemia | 2 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 1 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypophosphataemia | 2 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperkalaemia | 3 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypomagnesaemia | 8 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypokalaemia | 16 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Febrile neutropenia | 5 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 1 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 5 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Iron deficiency anaemia | 1 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Lymphopenia | 0 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Iron deficiency | 2 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Anaemia | 57 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Lymphocyte count decreased | 1 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | International normalised ratio increased | 1 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypercalcaemia | 6 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyponatraemia | 7 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Pancytopenia | 2 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Platelet count decreased | 6 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Creatinine renal clearance decreased | 2 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Neutrophil count decreased | 11 Participants |
| Placebo + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Blood creatinine increased | 9 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | White blood cell count decreased | 1 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 2 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Pancytopenia | 3 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Neutrophil count decreased | 5 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 0 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperuricaemia | 2 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Neutropenia | 15 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Anaemia | 53 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypophosphataemia | 9 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Thrombocytopenia | 34 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Blood creatinine increased | 6 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | International normalised ratio increased | 4 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypomagnesaemia | 6 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypokalaemia | 33 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyponatraemia | 10 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Iron deficiency anaemia | 1 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Leukopenia | 6 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperglycaemia | 7 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypocalcaemia | 6 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Lymphopenia | 7 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Febrile neutropenia | 7 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperkalaemia | 7 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 1 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Iron deficiency | 1 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Platelet count decreased | 6 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypercalcaemia | 2 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Lymphocyte count decreased | 2 Participants |
| Ixazomib + LenDex | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Creatinine renal clearance decreased | 1 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Iron deficiency anaemia | 1 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypokalaemia | 33 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Blood creatinine increased | 12 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | White blood cell count decreased | 3 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Lymphocyte count decreased | 3 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypophosphataemia | 3 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypomagnesaemia | 11 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyponatraemia | 8 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperglycaemia | 16 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypocalcaemia | 12 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperkalaemia | 3 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 4 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Iron deficiency | 2 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypercalcaemia | 1 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Creatinine renal clearance decreased | 7 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 1 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 3 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperuricaemia | 1 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Anaemia | 52 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Thrombocytopenia | 14 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Neutropenia | 48 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Neutrophil count decreased | 13 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Platelet count decreased | 4 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Lymphopenia | 2 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Febrile neutropenia | 2 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Leukopenia | 4 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | International normalised ratio increased | 0 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Pancytopenia | 1 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Neutrophil count decreased | 18 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Creatinine renal clearance decreased | 4 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypercalcaemia | 5 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Iron deficiency | 7 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Lymphocyte count decreased | 0 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Platelet count decreased | 15 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Alanine aminotransferase increased | 10 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypokalaemia | 39 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Lymphopenia | 4 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperkalaemia | 3 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypocalcaemia | 4 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Pancytopenia | 2 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Febrile neutropenia | 2 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperglycaemia | 6 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyponatraemia | 7 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | White blood cell count decreased | 2 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Leukopenia | 2 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypomagnesaemia | 15 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypophosphataemia | 9 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Iron deficiency anaemia | 4 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Thrombocytopenia | 24 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Anaemia | 58 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hyperuricaemia | 2 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | International normalised ratio increased | 4 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Neutropenia | 39 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Aspartate aminotransferase increased | 5 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Hypoalbuminaemia | 3 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs) | Blood creatinine increased | 16 Participants |
Secondary
Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score
Eastern Cooperative Oncology Group (ECOG) scale score ranged from 0 to 5, where 0 indicated normal activity and 5 indicated death. The data is reported for those categories where at least 1 participant had worst post-baseline value for each ECOG score.
Time frame: Up to approximately 9 years
Population: Safety population is defined as all participants who receive at least 1 dose of any study drug. Overall number of participants analyzed indicates number of participants available for analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 0, Post-Baseline Score 0 | 23 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 0, Post-Baseline Score 1 | 57 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 0, Post-Baseline Score 2 | 20 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 0, Post-Baseline Score 3 | 2 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 1, Post-Baseline Score 0 | 1 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 1, Post-Baseline Score 1 | 96 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 1, Post-Baseline Score 2 | 72 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 1, Post-Baseline Score 3 | 18 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 1, Post-Baseline Score 4 | 6 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 2, Post-Baseline Score 1 | 12 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 2, Post-Baseline Score 2 | 28 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 2, Post-Baseline Score 3 | 7 Participants |
| Placebo + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 2, Post-Baseline Score 4 | 2 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 2, Post-Baseline Score 2 | 35 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 0, Post-Baseline Score 0 | 23 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 1, Post-Baseline Score 3 | 9 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 0, Post-Baseline Score 1 | 52 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 2, Post-Baseline Score 4 | 3 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 0, Post-Baseline Score 2 | 23 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 1, Post-Baseline Score 4 | 4 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 0, Post-Baseline Score 3 | 10 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 2, Post-Baseline Score 3 | 11 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 1, Post-Baseline Score 0 | 1 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 2, Post-Baseline Score 1 | 8 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 1, Post-Baseline Score 1 | 104 Participants |
| Ixazomib + LenDex | Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score | Baseline Score 1, Post-Baseline Score 2 | 57 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.
Time frame: From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years)
Population: Safety population is defined as all participants who receive at least 1 dose of any study drug. Data for safety is summarized as per the duration of exposure to study treatment (exposure up to 18 cycles; exposure ≥19 cycles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo + LenDex | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 160 Participants |
| Placebo + LenDex | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 105 Participants |
| Ixazomib + LenDex | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 119 Participants |
| Ixazomib + LenDex | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 163 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 189 Participants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 119 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 191 Participants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 125 Participants |
Secondary
OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
OS was defined as the time from the date of randomization to the date of death, as assessed in high-risk population carrying del(17p), t(4;14), or t(14;16) mutations. High risk category includes t(4;14), t(14;16), or del(17) abnormalities.
Time frame: From the date of randomization to death due to any cause (Up to approximately 9 years)
Population: ITT population included all participants who were randomized. Overall number of participants analyzed indicates the number of participants from the high-risk category.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + LenDex | OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations | 43.1 months |
| Ixazomib + LenDex | OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations | 39.0 months |
Comparison: OS in High-risk Population Carrying Del(17p), Amp(1q21), t(4;14), or t(14;16) Mutationsp-value: 0.66295% CI: [0.678, 1.845]Log Rank
Secondary
Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved CR + partial response (PR) + very good partial response (VGPR) (including sCR) or better relative to the ITT population during treatment period. CR was defined as negative immunofixation of serum and urine along with the disappearance of any soft tissue plasmacytomas and \<5 % PC's in bone marrow. PR was defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% along with ≥50% reduction in the size of soft tissue plasmacytomas. VGPR was defined as ≥90% in serum M-component plus urine M-component \<100 mg/24. sCR is defined as stringent complete response. Percentages are rounded off to nearest whole numbers.
Time frame: Up to approximately 9 years
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + LenDex | Overall Response Rate (ORR) | 80 percentage of participants |
| Ixazomib + LenDex | Overall Response Rate (ORR) | 82 percentage of participants |
p-value: 0.43695% CI: [0.79, 1.7]Cochran-Mantel-Haenszel
Secondary
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death. Participants without documented death at the time of analysis are censored at the date last known to be alive.
Time frame: From the date of randomization to death due to any cause (Up to approximately 9 years)
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + LenDex | Overall Survival (OS) | NA months |
| Ixazomib + LenDex | Overall Survival (OS) | NA months |
p-value: 0.98895% CI: [0.79, 1.261]Log Rank
Secondary
Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use
Pain response rate was defined as percentage of participants with pain response. Pain response was defined as the occurrence of at least a 30% reduction from baseline in BPI-SF worst pain score over the last 24 hours without an increase in analgesic use for 2 consecutive measurements \> 28 days apart, were reported. Brief Pain Inventory - Short Form (m-BPI-SF) is a participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable). Percentages are rounded off to the nearest single decimal.
Time frame: Up to approximately 9 years
Population: ITT population included all participants who were randomized. Overall number of participants analyzed are the number of participants with baseline worst pain score\>=4 as assessed by m-BPI-SF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + LenDex | Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use | 51.3 percentage of participants |
| Ixazomib + LenDex | Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use | 50.5 percentage of participants |
p-value: 0.919595% CI: [0.656, 1.463]Regression, Logistic
Secondary
Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry
The absence of minimal residual disease (MRD negativity) was tested in all participants who achieve a CR and maintained it until Cycle 18, using bone marrow aspirates.
Time frame: Up to Cycle 18 (cycle length = 28 days)
Population: Response-evaluable population includes all participants in the ITT population who receive at least 1 dose of any study drug, have measurable disease at baseline, and at least 1 post baseline response assessment assessed by an IRC. Percentages are rounded off to the nearest single decimal.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + LenDex | Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry | 50 percentage of participants |
| Ixazomib + LenDex | Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry | 59 percentage of participants |
Secondary
Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs)
SRE is defined as new fractures \[including vertebral compression fractures\], irradiation of or surgery on bone, or spinal cord compression.
Time frame: From the date of randomization through 30 days after the last dose of study drug up to end of study (up to approximately 9 years)
Population: Safety population is defined as all participants who receive at least 1 dose of any study drug. Data for safety is summarized as per the duration of exposure to study treatment (exposure up to 18 cycles; exposure ≥19 cycles).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + LenDex | Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs) | 14 percentage of partcipants |
| Ixazomib + LenDex | Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs) | 10 percentage of partcipants |
| Placebo + LenDex (Exposure ≥19 Cycles) | Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs) | 28 percentage of partcipants |
| Ixazomib + LenDex (Exposure ≥19 Cycles) | Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs) | 25 percentage of partcipants |
Secondary
PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease based on central laboratory results and IMWG criteria as evaluated by an independent review committee (IRC) or death due to any cause, whichever occurs first, as assessed in high-risk population carrying del(17p), t(4;14), or t(14;16) mutations.
Time frame: Up to approximately 9 years
Population: ITT population included all participants who were randomized. Overall number of participants analyzed indicates the number of participants from the high-risk category.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + LenDex | PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations | 17.5 months |
| Ixazomib + LenDex | PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations | 22.4 months |
Comparison: PFS in High-risk Population Carrying del(17p), t(4;14), or t(14;16) Mutationsp-value: 0.27195% CI: [0.466, 1.24]Log Rank
Secondary
Progression Free Survival (PFS)-2
PFS2 was defined as the time from the date of randomization to the date of documentation of disease progression on the subsequent line of anticancer therapy, as assessed by the investigator in accordance with IMWG criteria, or death due to any cause, whichever occurs first.
Time frame: Up to approximately 9 years
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + LenDex | Progression Free Survival (PFS)-2 | 52.2 months |
| Ixazomib + LenDex | Progression Free Survival (PFS)-2 | 63.2 months |
p-value: 0.18995% CI: [0.684, 1.078]Log Rank
Secondary
Time to Pain Progression
Time to pain progression was assessed as the time from randomization to the date of initial progression classification. Pain progression was defined as the occurrence of 1 of the following and confirmed by 2 consecutive evaluations (To qualify as progression, the participant must have a BPI-SF worst pain score \> 4 during pain progression): 1) a ≥ 2 point and 30% increase from Baseline in BPI-SF worst pain score without an increase in analgesic use, or 2) a 25% or more increase in analgesic use from Baseline without a decrease in BPI-SF worst pain score from Baseline. Brief Pain Inventory - Short Form (m-BPI-SF) is a participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable).
Time frame: Up to approximately 9 years
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + LenDex | Time to Pain Progression | 47.1 months |
| Ixazomib + LenDex | Time to Pain Progression | NA months |
Comparison: Time to Pain Progressionp-value: 0.2695% CI: [0.661, 1.12]Log Rank
Secondary
Time to Progression (TTP)
Time to progression was defined as the time from randomization to the date of first documented disease progression.
Time frame: Up to approximately 9 years
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + LenDex | Time to Progression (TTP) | 26.8 months |
| Ixazomib + LenDex | Time to Progression (TTP) | 45.8 months |
p-value: 0.00895% CI: [0.589, 0.925]Log Rank
Secondary
Time to Response
Time to response was defined as the time from the date of randomization to the first documentation of PR or better, as measured by IMWG criteria.
Time frame: Up to approximately 9 years
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + LenDex | Time to Response | 1.87 months |
| Ixazomib + LenDex | Time to Response | 1.02 months |
p-value: <0.00195% CI: [1.185, 1.659]Log Rank