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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01850524




Registration number
NCT01850524
Ethics application status
Date submitted
26/04/2013
Date registered
9/05/2013

Titles & IDs
Public title
IXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma
Scientific 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
Secondary ID [1] 0 0
2013-000326-54
Secondary ID [2] 0 0
C16014
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ixazomib
Treatment: Drugs - Placebo
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Lenalidomide

Placebo comparator: 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).

Active comparator: Active Comparator: 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).


Treatment: Drugs: Ixazomib
IXAZOMIB capsules.

Treatment: Drugs: Placebo
IXAZOMIB matching-placebo capsules.

Treatment: Drugs: Dexamethasone
Dexamethasone tablets.

Treatment: Drugs: Lenalidomide
Lenalidomide capsules.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
Up to approximately 79 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From the date of randomization to death due to any cause (Up to approximately 9 years)
Secondary outcome [2] 0 0
Complete Response (CR) Rate
Timepoint [2] 0 0
Up to approximately 9 years
Secondary outcome [3] 0 0
Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use
Timepoint [3] 0 0
Up to approximately 9 years
Secondary outcome [4] 0 0
Overall Response Rate (ORR)
Timepoint [4] 0 0
Up to approximately 9 years
Secondary outcome [5] 0 0
Time to Response
Timepoint [5] 0 0
Up to approximately 9 years
Secondary outcome [6] 0 0
Duration of Response
Timepoint [6] 0 0
Up to approximately 9 years
Secondary outcome [7] 0 0
Time to Progression (TTP)
Timepoint [7] 0 0
Up to approximately 9 years
Secondary outcome [8] 0 0
Progression Free Survival (PFS)-2
Timepoint [8] 0 0
Up to approximately 9 years
Secondary outcome [9] 0 0
Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score
Timepoint [9] 0 0
Up to approximately 9 years
Secondary outcome [10] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs)
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
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
Timepoint [12] 0 0
Baseline to approximately 9 years
Secondary outcome [13] 0 0
Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale
Timepoint [13] 0 0
Baseline to approximately 9 years
Secondary outcome [14] 0 0
OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
Timepoint [14] 0 0
From the date of randomization to death due to any cause (Up to approximately 9 years)
Secondary outcome [15] 0 0
PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
Timepoint [15] 0 0
Up to approximately 9 years
Secondary outcome [16] 0 0
Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry
Timepoint [16] 0 0
Up to Cycle 18 (cycle length = 28 days)
Secondary outcome [17] 0 0
Time to Pain Progression
Timepoint [17] 0 0
Up to approximately 9 years
Secondary outcome [18] 0 0
Cmax: Maximum Plasma Concentration for Ixazomib
Timepoint [18] 0 0
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)
Secondary outcome [19] 0 0
Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs)
Timepoint [19] 0 0
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)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
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State/province [3] 0 0
Arkansas
Country [4] 0 0
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State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
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Connecticut
Country [7] 0 0
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Florida
Country [8] 0 0
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Georgia
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Hawaii
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Iowa
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Kentucky
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Louisiana
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Missouri
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New Jersey
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New Mexico
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New York
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Virginia
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Washington
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Belgium
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Brussels
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Belgium
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Namur
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Belgium
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Belgium
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Vlaams Brabant
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Belgium
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Bruges
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Belgium
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Liege
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Alberta
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Canada
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British Columbia
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Canada
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New Brunswick
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Nova Scotia
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Ontario
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Quebec
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Alpes-Maritimes
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Finistere
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Isere
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Meurthe-et-Moselle
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Morbihan
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Nord
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Pas-de-Calais
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Rhone
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Seine-Maritime
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Vienne
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Amiens
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Bayonne
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Bordeaux
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Caen
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Chalon sur Saone
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Creteil
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Dunkerque
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La Roche sur Yon
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France
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Le Chesnay
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Le Mans cedex 2
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Lille
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Montpellier cedex 5
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Mulhouse
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Paris
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Perigueux
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Pierre Benite
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Pontoise
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Rouen
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TOULOUSE Cedex 9
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France
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Tours
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Korea, Republic of
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Gyeonggido
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Korea, Republic of
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Daegu
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Korea, Republic of
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Daejeon
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Korea, Republic of
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Incheon
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Korea, Republic of
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Jeongnam
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Korea, Republic of
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Seoul
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New Zealand
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North Island
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New Zealand
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South Island
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New Zealand
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Hamilton
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Russian Federation
State/province [88] 0 0
Ryazan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Millennium Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director Clinical Science
Address 0 0
Millennium Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.