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IXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ixazomib
Placebo
Dexamethasone
Lenalidomide
Sponsored by
Millennium Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Newly Diagnosed multiple myeloma, multiple myeloma, MLN9708, IXAZOMIB, Proteasome inhibitor, Tourmaline MM2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo + LenDex

Active Comparator: Ixazomib + LenDex

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
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.
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.
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 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.
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 to Progression (TTP)
Time to progression was defined as the time from randomization to the date of first documented disease progression.
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.
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.
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.
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.
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.
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.
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.
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.
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 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).
Cmax: Maximum Plasma Concentration for Ixazomib
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.

Full Information

First Posted
April 26, 2013
Last Updated
July 20, 2023
Sponsor
Millennium Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01850524
Brief Title
IXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma
Official Title
A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral MLN9708 Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
April 29, 2013 (Actual)
Primary Completion Date
December 2, 2019 (Actual)
Study Completion Date
June 24, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Newly Diagnosed multiple myeloma, multiple myeloma, MLN9708, IXAZOMIB, Proteasome inhibitor, Tourmaline MM2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
705 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo + LenDex
Arm Type
Placebo Comparator
Arm Description
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).
Arm Title
Active Comparator: Ixazomib + LenDex
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Ixazomib
Other Intervention Name(s)
MLN9708
Intervention Description
IXAZOMIB capsules.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
IXAZOMIB matching-placebo capsules.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone tablets.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Lenalidomide capsules.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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)
Title
Complete Response (CR) Rate
Description
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
Title
Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use
Description
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
Title
Overall Response Rate (ORR)
Description
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
Title
Time to Response
Description
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
Title
Duration of Response
Description
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
Title
Time to Progression (TTP)
Description
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
Title
Progression Free Survival (PFS)-2
Description
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
Title
Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score
Description
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
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
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)
Title
Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs)
Description
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)
Title
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
Description
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
Title
Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale
Description
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
Title
OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
Description
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)
Title
PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
Description
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
Title
Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry
Description
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)
Title
Time to Pain Progression
Description
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
Title
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)
Title
Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs)
Description
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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. Measurable disease as specified in study protocol. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Meet the clinical laboratories criteria as specified in the protocol. 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. 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. Suitable venous access for the study-required blood sampling. Must be able to take concurrent aspirin 70 mg to 325 mg daily (or enoxaparin if aspirin allergic). Voluntary written consent. Participant is willing and able to adhere to the study visit schedule and other protocol requirements. Exclusion Criteria: Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen. 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. Inability or unwillingness to receive antithrombotic therapy. Female participants who are lactating or pregnant. Major surgery or radiotherapy within 14 days before randomization. Infection requiring intravenous antibiotics within 14 days before the first dose of study drug. Central nervous system involvement. 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. 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. 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. Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. 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). Psychiatric illness/social situation that would limit compliance with study requirements. Known allergy to any of the study medications. 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. Treatment with any investigational products within 60 days before randomization.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director Clinical Science
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
City
Birmingham
State/Province
Alabama
Country
United States
City
Chandler
State/Province
Arizona
Country
United States
City
Tucson
State/Province
Arizona
Country
United States
City
Little Rock
State/Province
Arkansas
Country
United States
City
Anaheim
State/Province
California
Country
United States
City
Corona
State/Province
California
Country
United States
City
Fountain Valley
State/Province
California
Country
United States
City
Fullerton
State/Province
California
Country
United States
City
Irvine
State/Province
California
Country
United States
City
La Jolla
State/Province
California
Country
United States
City
Mission Hills
State/Province
California
Country
United States
City
Oakland
State/Province
California
Country
United States
City
Riverside
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
San Jose
State/Province
California
Country
United States
City
San Leandro
State/Province
California
Country
United States
City
Santa Clara
State/Province
California
Country
United States
City
South San Francisco
State/Province
California
Country
United States
City
Vallejo
State/Province
California
Country
United States
City
Denver
State/Province
Colorado
Country
United States
City
Fort Collins
State/Province
Colorado
Country
United States
City
Hartford
State/Province
Connecticut
Country
United States
City
Plainville
State/Province
Connecticut
Country
United States
City
Fort Myers
State/Province
Florida
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
Miami Beach
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
West Palm Beach
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Marietta
State/Province
Georgia
Country
United States
City
Honolulu
State/Province
Hawaii
Country
United States
City
Iowa City
State/Province
Iowa
Country
United States
City
Sioux City
State/Province
Iowa
Country
United States
City
Louisville
State/Province
Kentucky
Country
United States
City
Shreveport
State/Province
Louisiana
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Towson
State/Province
Maryland
Country
United States
City
Burlington
State/Province
Massachusetts
Country
United States
City
Worcester
State/Province
Massachusetts
Country
United States
City
Ann Arbor
State/Province
Michigan
Country
United States
City
Lansing
State/Province
Michigan
Country
United States
City
Southfield
State/Province
Michigan
Country
United States
City
Duluth
State/Province
Minnesota
Country
United States
City
Minneapolis
State/Province
Minnesota
Country
United States
City
Rochester
State/Province
Minnesota
Country
United States
City
Bridgeton
State/Province
Missouri
Country
United States
City
Kansas City
State/Province
Missouri
Country
United States
City
Little Silver
State/Province
New Jersey
Country
United States
City
Albuquerque
State/Province
New Mexico
Country
United States
City
Farmington
State/Province
New Mexico
Country
United States
City
Las Cruces
State/Province
New Mexico
Country
United States
City
Buffalo
State/Province
New York
Country
United States
City
Lake Success
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Poughkeepsie
State/Province
New York
Country
United States
City
Cincinnati
State/Province
Ohio
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Tulsa
State/Province
Oklahoma
Country
United States
City
Eugene
State/Province
Oregon
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Hershey
State/Province
Pennsylvania
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
Scranton
State/Province
Pennsylvania
Country
United States
City
Charleston
State/Province
South Carolina
Country
United States
City
Cookeville
State/Province
Tennessee
Country
United States
City
Nashville
State/Province
Tennessee
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
Galveston
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Temple
State/Province
Texas
Country
United States
City
Tyler
State/Province
Texas
Country
United States
City
Christiansburg
State/Province
Virginia
Country
United States
City
Richmond
State/Province
Virginia
Country
United States
City
Everett
State/Province
Washington
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Spokane
State/Province
Washington
Country
United States
City
Vancouver
State/Province
Washington
Country
United States
City
Yakima
State/Province
Washington
Country
United States
City
Brussel
State/Province
Brussels
Country
Belgium
City
Bruxelles
State/Province
Brussels
Country
Belgium
City
Yvoir
State/Province
Namur
Country
Belgium
City
Gent
State/Province
Oost-Vlaanderen
Country
Belgium
City
Leuven
State/Province
Vlaams Brabant
Country
Belgium
City
Roeselare
State/Province
West-Vlaanderen
Country
Belgium
City
Bruges
Country
Belgium
City
Liege
Country
Belgium
City
Calgary
State/Province
Alberta
Country
Canada
City
Edmonton
State/Province
Alberta
Country
Canada
City
Surrey
State/Province
British Columbia
Country
Canada
City
Victoria
State/Province
British Columbia
Country
Canada
City
St. John
State/Province
New Brunswick
Country
Canada
City
Halifax
State/Province
Nova Scotia
Country
Canada
City
Hamilton
State/Province
Ontario
Country
Canada
City
London
State/Province
Ontario
Country
Canada
City
Toronto
State/Province
Ontario
Country
Canada
City
Fleurimont
State/Province
Quebec
Country
Canada
City
Levis
State/Province
Quebec
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada
City
Nice
State/Province
Alpes-Maritimes
Country
France
City
Strasbourg
State/Province
Bas-Rhin
Country
France
City
Brest
State/Province
Finistere
Country
France
City
Saint-Brieuc
State/Province
Finistere
Country
France
City
Limoges
State/Province
Haute-Vienne
Country
France
City
Castelnau-le-Lez
State/Province
Herault
Country
France
City
La Tronche
State/Province
Isere
Country
France
City
Nantes
State/Province
Loire-Atlantique
Country
France
City
Angers
State/Province
Maine-et-Loire
Country
France
City
Reims
State/Province
Marne
Country
France
City
Vandoeuvre-les-nancy
State/Province
Meurthe-et-Moselle
Country
France
City
Vannes
State/Province
Morbihan
Country
France
City
Lille Cedex
State/Province
Nord
Country
France
City
Lens
State/Province
Pas-de-Calais
Country
France
City
Saint-priest-en-jarez
State/Province
Rhone
Country
France
City
Montivilliers
State/Province
Seine-Maritime
Country
France
City
Poitiers
State/Province
Vienne
Country
France
City
Amiens
Country
France
City
Bayonne
Country
France
City
Bordeaux
Country
France
City
Caen
Country
France
City
Chalon sur Saone
Country
France
City
Creteil
Country
France
City
Dunkerque
Country
France
City
La Roche sur Yon
Country
France
City
Le Chesnay
Country
France
City
Le Mans cedex 2
Country
France
City
Lille
Country
France
City
Montpellier cedex 5
Country
France
City
Mulhouse
Country
France
City
Paris
Country
France
City
Perigueux
Country
France
City
Pierre Benite
Country
France
City
Pontoise
Country
France
City
Rouen
Country
France
City
TOULOUSE Cedex 9
Country
France
City
Tours
Country
France
City
Goyang
State/Province
Gyeonggido
Country
Korea, Republic of
City
Seongnam-si
State/Province
Gyeonggido
Country
Korea, Republic of
City
Daegu
Country
Korea, Republic of
City
Daejeon
Country
Korea, Republic of
City
Incheon
Country
Korea, Republic of
City
Jeongnam
Country
Korea, Republic of
City
Seoul
Country
Korea, Republic of
City
Auckland
State/Province
North Island
Country
New Zealand
City
Wellington
State/Province
North Island
Country
New Zealand
City
Christchurch
State/Province
South Island
Country
New Zealand
City
Dunedin
State/Province
South Island
Country
New Zealand
City
Hamilton
Country
New Zealand
City
Ryazan
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Citations:
PubMed Identifier
33763699
Citation
Facon T, Venner CP, Bahlis NJ, Offner F, White DJ, Karlin L, Benboubker L, Rigaudeau S, Rodon P, Voog E, Yoon SS, Suzuki K, Shibayama H, Zhang X, Twumasi-Ankrah P, Yung G, Rifkin RM, Moreau P, Lonial S, Kumar SK, Richardson PG, Rajkumar SV. Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. Blood. 2021 Jul 1;137(26):3616-3628. doi: 10.1182/blood.2020008787.
Results Reference
derived
Links:
URL
https://www.tourmalinetrialmm2.com
Description
Related Info

Learn more about this trial

IXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma

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