IXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma
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
4 other identifiers
interventional
705
7 countries
147
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 multiple-myeloma
Started Apr 2013
Longer than P75 for phase_3 multiple-myeloma
147 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 26, 2013
CompletedStudy Start
First participant enrolled
April 29, 2013
CompletedFirst Posted
Study publicly available on registry
May 9, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 2, 2019
CompletedResults Posted
Study results publicly available
February 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 24, 2022
CompletedJuly 21, 2023
July 1, 2023
6.6 years
April 26, 2013
November 20, 2020
July 20, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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).
Up to approximately 79 months
Secondary Outcomes (19)
Overall Survival (OS)
From the date of randomization to death due to any cause (Up to approximately 9 years)
Complete Response (CR) Rate
Up to approximately 9 years
Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use
Up to approximately 9 years
Overall Response Rate (ORR)
Up to approximately 9 years
Time to Response
Up to approximately 9 years
- +14 more secondary outcomes
Study Arms (2)
Placebo + LenDex
PLACEBO COMPARATORParticipants 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: Ixazomib + LenDex
ACTIVE COMPARATORParticipants 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).
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (147)
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Birmingham, Alabama, United States
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Chandler, Arizona, United States
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Tucson, Arizona, United States
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Little Rock, Arkansas, United States
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Anaheim, California, United States
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Corona, California, United States
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Fountain Valley, California, United States
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Fullerton, California, United States
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Irvine, California, United States
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La Jolla, California, United States
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Mission Hills, California, United States
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Oakland, California, United States
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Riverside, California, United States
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San Diego, California, United States
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San Jose, California, United States
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San Leandro, California, United States
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Santa Clara, California, United States
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South San Francisco, California, United States
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Vallejo, California, United States
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Denver, Colorado, United States
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Fort Collins, Colorado, United States
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Hartford, Connecticut, United States
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Plainville, Connecticut, United States
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Fort Myers, Florida, United States
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Jacksonville, Florida, United States
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Miami, Florida, United States
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Miami Beach, Florida, United States
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West Palm Beach, Florida, United States
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Atlanta, Georgia, United States
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Marietta, Georgia, United States
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Honolulu, Hawaii, United States
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Iowa City, Iowa, United States
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Sioux City, Iowa, United States
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Louisville, Kentucky, United States
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Shreveport, Louisiana, United States
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Baltimore, Maryland, United States
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Towson, Maryland, United States
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Burlington, Massachusetts, United States
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Worcester, Massachusetts, United States
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Ann Arbor, Michigan, United States
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Lansing, Michigan, United States
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Southfield, Michigan, United States
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Duluth, Minnesota, United States
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Minneapolis, Minnesota, United States
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Rochester, Minnesota, United States
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Bridgeton, Missouri, United States
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Kansas City, Missouri, United States
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Little Silver, New Jersey, United States
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Albuquerque, New Mexico, United States
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Farmington, New Mexico, United States
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Las Cruces, New Mexico, United States
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Buffalo, New York, United States
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Lake Success, New York, United States
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New York, New York, United States
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Poughkeepsie, New York, United States
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Cincinnati, Ohio, United States
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Cleveland, Ohio, United States
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Tulsa, Oklahoma, United States
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Eugene, Oregon, United States
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Portland, Oregon, United States
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Hershey, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Scranton, Pennsylvania, United States
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Charleston, South Carolina, United States
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Cookeville, Tennessee, United States
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Nashville, Tennessee, United States
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Austin, Texas, United States
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Galveston, Texas, United States
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San Antonio, Texas, United States
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Temple, Texas, United States
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Tyler, Texas, United States
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Christiansburg, Virginia, United States
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Richmond, Virginia, United States
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Everett, Washington, United States
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Seattle, Washington, United States
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Spokane, Washington, United States
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Vancouver, Washington, United States
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Yakima, Washington, United States
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Brussels, Brussels Capital, Belgium
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Yvoir, Namur, Belgium
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Ghent, Oost-Vlaanderen, Belgium
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Leuven, Vlaams Brabant, Belgium
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Roeselare, West-Vlaanderen, Belgium
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Bruges, Belgium
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Liège, Belgium
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Calgary, Alberta, Canada
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Edmonton, Alberta, Canada
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Surrey, British Columbia, Canada
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Victoria, British Columbia, Canada
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Saint John, New Brunswick, Canada
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Halifax, Nova Scotia, Canada
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Hamilton, Ontario, Canada
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London, Ontario, Canada
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Toronto, Ontario, Canada
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Fleurimont, Quebec, Canada
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Lévis, Quebec, Canada
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Montreal, Quebec, Canada
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Nice, Alpes-Maritimes, France
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Strasbourg, Bas-Rhin, France
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Brest, Finistere, France
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Saint-Brieuc, Finistere, France
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Limoges, Haute-Vienne, France
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Castelnau-le-Lez, Herault, France
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La Tronche, Isere, France
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Nantes, Loire-Atlantique, France
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Angers, Maine-et-Loire, France
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Reims, Marne, France
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Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France
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Vannes, Morbihan, France
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Lille, Nord, France
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Lens, Pas-de-Calais, France
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Saint-Priest-en-Jarez, Rhone, France
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Montivilliers, Seine-Maritime, France
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Poitiers, Vienne, France
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Amiens, France
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Bayonne, France
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Bordeaux, France
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Caen, France
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Chalon-sur-Saône, France
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Créteil, France
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Dunkirk, France
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La Roche-sur-Yon, France
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Le Chesnay, France
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Le Mans, France
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Lille, France
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Montpellier, France
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Mulhouse, France
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Paris, France
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Périgueux, France
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Pierre-Bénite, France
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Pontoise, France
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Rouen, France
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Toulouse, France
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Tours, France
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Auckland, North Island, New Zealand
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Wellington, North Island, New Zealand
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Christchurch, South Island, New Zealand
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Dunedin, South Island, New Zealand
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Hamilton, New Zealand
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Ryazan, Russia
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Goyang, Gyeonggido, South Korea
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Seongnam-si, Gyeonggido, South Korea
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Daegu, South Korea
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Daejeon, South Korea
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Incheon, South Korea
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Jeongnam, South Korea
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Seoul, South Korea
Related Publications (1)
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.
PMID: 33763699DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director Clinical Science
Millennium Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 26, 2013
First Posted
May 9, 2013
Study Start
April 29, 2013
Primary Completion
December 2, 2019
Study Completion
June 24, 2022
Last Updated
July 21, 2023
Results First Posted
February 1, 2021
Record last verified: 2023-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- 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.
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.