Clinical trial NCT01850524: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Newly Diagnosed multiple myeloma
multiple myeloma
MLN9708
IXAZOMIB
Proteasome inhibitor
Tourmaline MM2
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2013-05-09
Enrollment: 705
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to approximately 79 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of randomization to death due to any cause (Up to approximately 9 years)
measure: Complete Response (CR) Rate
timeFrame: Up to approximately 9 years
measure: Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use
timeFrame: Up to approximately 9 years
measure: Overall Response Rate (ORR)
timeFrame: Up to approximately 9 years
measure: Time to Response
timeFrame: Up to approximately 9 years
measure: Duration of Response
timeFrame: Up to approximately 9 years
measure: Time to Progression (TTP)
timeFrame: Up to approximately 9 years
measure: Progression Free Survival (PFS)-2
timeFrame: Up to approximately 9 years
measure: Number of Participants With Shifts From Baseline to Worst Value in Eastern Cooperative Oncology Group (ECOG) Performance Score
timeFrame: Up to approximately 9 years
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Number of Participants With Abnormal Serum Chemistry and Hematology Laboratory Values Based on Treatment-emergent Adverse Events (TEAEs)
timeFrame: 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)
measure: 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
timeFrame: Baseline to approximately 9 years
measure: Change From Baseline in HRQOL Measured by EORTC-QLQ-MY20 Scale
timeFrame: Baseline to approximately 9 years
measure: OS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
timeFrame: From the date of randomization to death due to any cause (Up to approximately 9 years)
measure: PFS in High-risk Population Carrying Del(17p), t(4;14), or t(14;16) Mutations
timeFrame: Up to approximately 9 years
measure: Percentage of Participants With MRD-Negative Status as Assessed by Flow Cytometry
timeFrame: Up to Cycle 18 (cycle length = 28 days)
measure: Time to Pain Progression
timeFrame: Up to approximately 9 years
measure: Cmax: Maximum Plasma Concentration for Ixazomib
timeFrame: 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)
measure: Percentage of Participants With New or Worsening of Existing Skeletal-related Events (SREs)
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Anaheim
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state: California
city: Corona
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state: California
city: Fountain Valley
country: United States
state: California
city: Fullerton
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state: California
city: Irvine
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state: California
city: La Jolla
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state: California
city: Mission Hills
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state: California
city: Oakland
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state: California
city: Riverside
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state: California
city: San Diego
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state: California
city: San Jose
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state: California
city: San Leandro
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state: California
city: Santa Clara
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state: California
city: South San Francisco
country: United States
state: California
city: Vallejo
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Fort Collins
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: Plainville
country: United States
state: Connecticut
city: Fort Myers
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami Beach
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: West Palm Beach
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Iowa City
country: United States
state: Iowa
city: Sioux City
country: United States
state: Iowa
city: Louisville
country: United States
state: Kentucky
city: Shreveport
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Towson
country: United States
state: Maryland
city: Burlington
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Lansing
country: United States
state: Michigan
city: Southfield
country: United States
state: Michigan
city: Duluth
country: United States
state: Minnesota
city: Minneapolis
country: United States
state: Minnesota
city: Rochester
country: United States
state: Minnesota
city: Bridgeton
country: United States
state: Missouri
city: Kansas City
country: United States
state: Missouri
city: Little Silver
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Farmington
country: United States
state: New Mexico
city: Las Cruces
country: United States
state: New Mexico
city: Buffalo
country: United States
state: New York
city: Lake Success
country: United States
state: New York
city: New York
country: United States
state: New York
city: Poughkeepsie
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Eugene
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Hershey
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Scranton
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Cookeville
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Galveston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Temple
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Christiansburg
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Everett
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Vancouver
country: United States
state: Washington
city: Yakima
country: United States
state: Washington
city: Brussel
country: Belgium
state: Brussels
city: Bruxelles
country: Belgium
state: Brussels
city: Yvoir
country: Belgium
state: Namur
city: Gent
country: Belgium
state: Oost-Vlaanderen
city: Leuven
country: Belgium
state: Vlaams Brabant
city: Roeselare
country: Belgium
state: West-Vlaanderen
city: Bruges
country: Belgium
city: Liege
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Surrey
country: Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: St. John
country: Canada
state: New Brunswick
city: Halifax
country: Canada
state: Nova Scotia
city: Hamilton
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Fleurimont
country: Canada
state: Quebec
city: Levis
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Nice
country: France
state: Alpes-Maritimes
city: Strasbourg
country: France
state: Bas-Rhin
city: Brest
country: France
state: Finistere
city: Saint-Brieuc
country: France
state: Finistere
city: Limoges
country: France
state: Haute-Vienne
city: Castelnau-le-Lez
country: France
state: Herault
city: La Tronche
country: France
state: Isere
city: Nantes
country: France
state: Loire-Atlantique
city: Angers
country: France
state: Maine-et-Loire
city: Reims
country: France
state: Marne
city: Vandoeuvre-les-nancy
country: France
state: Meurthe-et-Moselle
city: Vannes
country: France
state: Morbihan
city: Lille Cedex
country: France
state: Nord
city: Lens
country: France
state: Pas-de-Calais
city: Saint-priest-en-jarez
country: France
state: Rhone
city: Montivilliers
country: France
state: Seine-Maritime
city: Poitiers
country: France
state: Vienne
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
country: Korea, Republic of
state: Gyeonggido
city: Seongnam-si
country: Korea, Republic of
state: Gyeonggido
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
country: New Zealand
state: North Island
city: Wellington
country: New Zealand
state: North Island
city: Christchurch
country: New Zealand
state: South Island
city: Dunedin
country: New Zealand
state: South Island
city: Hamilton
country: New Zealand
city: Ryazan
country: Russian Federation
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
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.