A Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT)

• ClinicalTrials.gov Identifier: NCT02312258
• Recruitment Status: Completed
• First Posted: December 9, 2014
• Results First Posted: November 10, 2020
• Last Update Posted: January 18, 2023
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

Brief Summary:

The purpose of this study is to determine the effect of ixazomib maintenance therapy on progression free survival (PFS) compared with placebo, in participants with NDMM who have had a major response (complete response [CR], very good partial response [VGPR], or partial response [PR]) to initial therapy and who have not undergone SCT.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Placebo; Drug: Ixazomib	Phase 3

Detailed Description:

The drug being tested in this study is called ixazomib citrate. Ixazomib citrate is being tested to slow progressive disease (PD) and improve overall survival in people who have NDMM who have had a major positive response to initial therapy and have not undergone SCT. This study will look at the effect of ixazomib citrate has on the length of time that participants are free of PD and their overall survival.

The study will enrol approximately 700 participants. Participants will be randomly assigned (by chance, like flipping a coin) in 3:2 ratio to Ixazomib or matching placebo groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

• Ixazomib citrate initiates at 3 mg which will be escalated to 4 mg with cycle 5 day 1
• Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has no active ingredient

All participants will be asked to take one capsule on Days 1, 8 and 15 of each 28-day cycle. The treatment period will be approximately 24 months (equivalent to 26 cycles) or until patients experience PD or unacceptable toxicities, whichever occurs first.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 78 to 106 months. Participants will make 28 visits to the clinic during the treatment period and will continue to make follow-up visits every 4 weeks until the next line of therapy begins. Participants will also be contacted by telephone every 12 weeks after last treatment visit for a follow-up assessment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 706 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation
• Actual Study Start Date: April 9, 2015
• Actual Primary Completion Date: August 12, 2019
• Actual Study Completion Date: August 26, 2022

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Ixazomib placebo-matching capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib placebo-matching capsules, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019).	Drug: Placebo; Ixazomib placebo-matching capsules.
Experimental: Ixazomib; Ixazomib 3 mg, capsule, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib 3 or 4 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 (1st interim analysis data cut-off 12 August 2019).	Drug: Ixazomib; Ixazomib capsules.

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: From the randomization until progressive disease (PD) or death or data cut-off date (12 Aug 2019) (Up to approximately 42 months) ]
   PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first. Per IMWG criteria, PD definition: increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/dl); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved FLC levels (absolute increase >10 mg/dl); or bone marrow plasma cell percentage (absolute plasma cell percentage ≥10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia (corrected serum calcium >11.5mg/dl).

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: From the date of randomization every 12 weeks after PD on next-line therapy until death (Up to approximately 76 to 104 months) ]
   OS will be measured as the time from the date of randomization to the date of death.
2. Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period [ Time Frame: Up to 24 months ]
   Response will be assessed according to IMWG criteria. Best response includes PR, VGPR and CR.
3. Time to Progression (TTP) [ Time Frame: From the date of randomization to the date of first documented PD (Up to approximately 76 to 104 months) ]
   TTP is defined as the time from the date of randomization to the date of first documentation of PD, using IMWG criteria.
4. Progression Free Survival 2 (PFS2) [ Time Frame: From the date of randomization to every 12 weeks until 2nd PD or death (Up to approximately 76 to 104 months) ]
   PFS2 is defined as the time from the date of randomization to objective PD on next-line treatment using IMWG criteria, or death due to any cause, whichever occurs first.
5. Time to Next Line Therapy (TTNT) [ Time Frame: From the date of randomization to the date of the first dose of the next-line of therapy (Up to approximately 76 to 104 months) ]
   TTNT is defined as the time from the date of randomization to the date of the first dose of next-line antineoplastic therapy.
6. Time to End of the Next-line of Therapy After Study Treatment [ Time Frame: From the date of randomization to the date of last dose of the next-line of therapy (Up to approximately 76 to 104 months) ]
   Time to end of the next line of therapy is defined as the time from the date of randomization to the date of last dose of the next line of antineoplastic therapy following study treatment.
7. Duration of Next-line Therapy [ Time Frame: From the date of the first dose of the line of antineoplastic therapy coming after study treatment to the date of the last dose (Up to approximately 76 to 104 months) ]
   Duration of next-line therapy is defined as the time from the date of the first dose of the line of antineoplastic therapy coming after study treatment to the date of the last dose.
8. Percentage of Participants Who Develop A New Primary Malignancy [ Time Frame: From the randomization date till death or termination of the study (Up to approximately 76 to 104 months) ]
9. Percentage of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative, or the Maintenance of MRD Negativity [ Time Frame: Screening, Cycle 13, and Cycle 26 (Cycle length is equal to [=] 28 days) ]
   Bone marrow aspirates and blood samples will be sent to a central laboratory and will be assessed for MRD using flow cytometry. MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD.
10. Correlation of MRD Status With PFS and OS [ Time Frame: Screening, Cycle 13, and Cycle 26 (Cycle length=28 days) ]
    PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurs first. OS will be measured as the time from the date of randomization to the date of death.
11. OS in a High-risk Population [ Time Frame: From the date of randomization to every 12 weeks after PD on next-line therapy until death (Up to approximately 76 to 104 months) ]
    High-risk population will include but not be limited to participants carrying deletion (del)17, t(4;14), t(14;16). OS will be measured as the time from the date of randomization to the date of death.
12. PFS in a High-risk Population [ Time Frame: From the date of randomization to every 4 weeks during follow-up until PD or death (Up to approximately 76 to 104 months) ]
    High-risk population will include but not be limited to participants carrying del17, t(4;14), t(14;16). PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause.
13. Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Cycle 2 and every 28 days ( Up to 24 months) (Cycle length =28 days) ]
    ECOG performance status assess participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory ( greater than [>] 50 percent [%] of waking hours), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead.
14. Percentage of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) [ Time Frame: First dose of study drug through 30 days after last dose of study drug (Up to 25 months) ]
    AEs are defined as any unfavourable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug. A SAE means any untoward medical occurrence that results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is considered medically significant.
15. Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline and every 28 days (Up to 24 months) ]
    The EORTC QLQ-C30 is completed by the participant. The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best).
16. Number of Participants With Any Markedly Abnormal Standard Safety Laboratory Values [ Time Frame: From First dose date of study drug through 30 days after the last dose of study drug (Up to 25 months) ]
    Clinical laboratory evaluations will be performed by a central laboratory. The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.
17. Correlation Between Frailty Status and PFS and OS [ Time Frame: Up to approximately 76 to 104 months ]
    Participant's frailty status is classified as fit, unfit or frail on the bases of 4 components: age, the Charlson comorbidity scoring system without age weighting, the Katz index of independence in activities of daily living, and the Lawton instrumental activities of daily living scale. The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from the date of randomization to the date of first documentation of PD or death from any cause, as evaluated by an IRC according to IMWG criteria, or death due to any cause, whichever occurs first. OS will be measured as the time from the date of randomization to the date of death.
18. Pharmacokinetic Parameter: Plasma Concentration of Ixazomib [ Time Frame: Cycle 1 (1 and 4 hours post-dose Day 1, Days 8 and 15 pre-dose); Cycle 2 and 5 (Days 1 and 8 pre-dose) and Cycles 3, 4, 6-10 (Day 1 pre-dose) (Cycle length =28 days) ]
    Plasma concentrations of the complete hydrolysis product of ixazomib citrate (ixazomib) will be measured using a validated Liquid Chromatography-tandem Mass Spectrometry (LC/MS/MS) assay.
19. Time to Resolution of Peripheral Neuropathy (PN) Events [ Time Frame: From the initial onset date of PN up to the resolution date for resolved events (Up to 25 Months) ]
    PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the Medical Dictionary for Regulatory Activities (MedDRA). A PN event is considered as resolved if its final outcome is resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. Time to resolution is defined as the time from the initial onset date (inclusive) to the resolution date for resolved events.
20. Time to Improvement of PN Events [ Time Frame: From the initial onset date of PN up to the improvement of event (Up to 25 Months) ]
    PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies NEC according to the MedDRA. A PN event is considered as resolved if its final outcome is resolved with no subsequent PN event of the same preferred term occurring on the improvement date or the day before and after. Time to improvement is defined as the time from the initial onset date (inclusive) to the improvement of event.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic newly diagnosed multiple myeloma (NDMM) according to standard criteria.
2. Completed 6 to 12 months (± 2 weeks) of initial therapy, during which the participant was treated to best response, defined as the best response maintained for 2 cycles after the M-protein nadir is reached.
3. Documented major response (PR, VGPR, CR) according to the International Myeloma Working Group (IMWG) uniform response criteria, version 2011, after this initial therapy.

4. Female participants who:

   • Are postmenopausal for at least 1 year before the screening visit, OR
   • Are surgically sterile, OR
   • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, OR
   • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)

   Male participants, even if surgically sterilized (that is, status postvasectomy), who:

   • Agree to practice effective barrier contraception during the entire study Treatment period and through 90 days after the last dose of study drug, OR
   • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
5. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
6. Complete documentation of the details of the initial therapy before randomization including cytogenetics and International Staging System (ISS) is available.
7. Eastern Cooperative Oncology Group Performance Status of 0 to 2.
8. Suitable venous access for the study-required blood sampling and consent for the specific amounts that will be taken.
9. Is willing and able to adhere to the study visit schedule and other protocol requirements including blood sampling and bone marrow aspiration.

10. Must meet the following clinical laboratory criteria at study entry:

    • Absolute neutrophil count (ANC) greater than or equal to (≥) 1,000 per cubic millimeter (/mm^3) without growth factor support and platelet count ≥75,000/mm^3. Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days before randomization.
    • Total bilirubin less than or equal to (≤) 1.5*the upper limit of the normal range (ULN).
    • Alanine aminotransferase and aspartate aminotransferase ≤ 3*ULN.
    • Calculated creatinine clearance ≥ 30 milliliter per minute (mL/min) (using the Cockcroft-Gault equation).

Exclusion Criteria:

1. Multiple myeloma that has relapsed after, or was not responsive to, initial therapy.
2. Prior SCT.
3. Radiotherapy within 14 days before randomization.
4. Diagnosed or treated for another malignancy within 5 years before randomization or previous diagnosis with another malignancy. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
5. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
6. Major surgery within 14 days before randomization.
7. Central nervous system involvement.
8. Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before randomization.
9. Diagnosis of Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome (POEMS), plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
10. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, uncontrolled congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
11. Systemic treatment with strong cytochrome P450 3A (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or St. John's wort within 14 days before randomization.
12. Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active hepatitis B or C infection.
13. Comorbid systemic illnesses or other severe concurrent disease that, 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 (example, PN that is Grade 1 with pain or Grade 2 or higher of any cause).
14. Psychiatric illness or social situation that would limit compliance with study requirements.
15. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
16. 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.
17. Treatment with any investigational products within 30 days before randomization.

Contacts and Locations

Locations

United States, California

Robert A Moss MD FACP Inc

Fountain Valley, California, United States, 92708

UCLA Medical Hematology and Oncology

Los Angeles, California, United States, 90095

North County Oncology Medical Clinic Inc

Oceanside, California, United States, 92056

Ventura County Hematology Oncology Specialists

Oxnard, California, United States, 93030

Emad Ibrahim, MD, Inc

Redlands, California, United States, 92373

Global Cancer Research Institute (GCRI), Inc.

San Jose, California, United States, 95124

Central Coast Medical Oncology Corporation

Santa Maria, California, United States, 93454

United States, Georgia

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

John H. Stroger Jr. Hospital of Cook County

Chicago, Illinois, United States, 60612

United States, Iowa

Siouxland Hematology - Oncology Associates LLP

Sioux City, Iowa, United States, 51101

United States, Kentucky

Appalachian Regional Healthcare

Hazard, Kentucky, United States, 41701

United States, Maine

New England Cancer Specialists

Scarborough, Maine, United States, 04074

United States, Maryland

Saint Agnes Hospital - Baltimore - Hunt - PPDS

Baltimore, Maryland, United States, 21229

University Hospital of Wales -

Bethesda, Maryland, United States, 20817

United States, Massachusetts

Tufts Medical Center - PPDS

Boston, Massachusetts, United States, 02111

United States, Michigan

Herbert-Herman Cancer Center

Lansing, Michigan, United States, 48912

United States, New York

Clinical Research Alliance Inc

New York, New York, United States, 10021

New York Presbyterian Hospital - Weill-Cornell

New York, New York, United States, 10021

United States, North Carolina

Cancer Care of WNC PA

Asheville, North Carolina, United States, 28801

United States, Pennsylvania

UPMC Cancer Pavillion

Pittsburgh, Pennsylvania, United States, 15232

United States, Texas

HOPE Cancer Center of East Texas

Tyler, Texas, United States, 75701

United States, Washington

Swedish Cancer Institute

Seattle, Washington, United States, 98109

United States, West Virginia

W VA University Mary Babb Randolph Cancer Center

Morgantown, West Virginia, United States, 26506

Argentina

Hospital Universitario Austral

Buenos Aires, Ciudad Autonoma De BuenosAires, Argentina, B1629AHJ

Hospital Italiano de Buenos Aires

Buenos Aires, Ciudad Autonoma De BuenosAires, Argentina, C1181ACH

Centro de Educacion Medica e Investigaciones Clinicas "Norberto Quirno" (CEMIC)

Buenos Aires, Ciudad Autonoma De BuenosAires, Argentina, C1431FWO

Sanatorio Allende S.A.

Cordoba, Argentina, X5000JHQ

Hospital Iturraspe

Santa Fe, Argentina, S3000ADL

Australia, Victoria

St Vincents Hospital Melbourne - PPDS

Fitzroy, Victoria, Australia, 3065

Frankston Hospital

Frankston, Victoria, Australia, 3199

The Alfred Hospital

Melbourne, Victoria, Australia, 3004

Austria

Universitatsklinikum Innsbruck

Innsbruck, Tirol, Austria, 6020

Paracelsus Medizinische Privatuniversitat

Salzburg, Austria, 5020

Klinikum Wels-Grieskirchen GmbH

Wels, Austria, 4600

Medizinische Universitat Wien (Medical University of Vienna)

Wien, Austria, A-1090

Belgium

Universitair Ziekenhuis Brussel - PIN

Brussel, Brussels, Belgium, 1090

UZ Brussel

Brussel, Brussels, Belgium, 1090

Cliniques Universitaires Saint-Luc

Bruxelles, Brussels, Belgium, 1200

Brazil

Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet

Salvador, Bahia, Brazil, 41253-196

Hospital Das Clinicas Da Universidade Federal de Goias

Goiania, Goias, Brazil, 74605-020

Hospital Das Clinicas Da UFMG

Belo Horizonte, Minas Gerais, Brazil, 30130-100

Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner

Curitiba, Parana, Brazil, 81520-060

Liga Norte Riograndense Contra O Cancer

Natal, Rio Grande Do Norte, Brazil, 59040-150

Universidade de Caxias do Sul

Caxias Do Sul, Rio Grande Do Sul, Brazil, 95070-560

Associacao Hospital de Caridade Ijui

Ijui, Rio Grande Do Sul, Brazil, 98700-000

American Oncology Partners of Maryland, PA

Passo Fundo, Rio Grande Do Sul, Brazil, 99010-260

Hospital Moinhos de Vento

Porto Alegre, Rio Grande Do Sul, Brazil, 90035-001

Hospital de Clinicas de Porto Alegre (HCPA) - PPDS

Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903

Mae de Deus Center Hospital Giovanni Battista

Porto Alegre, Rio Grande Do Sul, Brazil, 90470-340

Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)

Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000

Instituto Joinvilense de Hematologia E Oncologia

Joinville, Santa Catarina, Brazil, 89201260

Fundacao PIO XII

Barretos, Sao Paulo, Brazil, 14784-400

Universidade Estadual de Campinas

Campinas, Sao Paulo, Brazil, 13083-878

Hospital Amaral Carvalho

Jau, Sao Paulo, Brazil, 17210-120

Faculdade de Medicina Do ABC

Santo Andre, Sao Paulo, Brazil, 09060-650

HEMORIO - Unidade de Pesquisa Clinica

Rio De Janeiro, Brazil, 20211-030

Instituto Nacional de Cancer

Rio de Janeiro, Brazil, 20231-050

Fundação Antônio Prudente - AC Camargo Câncer Center

Rio De Janeiro, Brazil, 21941-913

Hospital de Base Da Faculdade de Medicina de Sao Jose Do Rio Preto

Sao Jose Do Rio Preto, Brazil, 15090-000

Instituto de Ensino E Pesquisa Sao Lucas

Sao Paulo, Brazil, 01236-030

Hospital Sirio Libanes

Sao Paulo, Brazil, 01308-050

Ealing Hospital

Sao Paulo, Brazil, 01509-900

Clinica Sao Germano

Sao Paulo, Brazil, 04537-080

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo

Sao Paulo, Brazil, 05403-000

Hospital Israelita Albert Einstein

Sao Paulo, Brazil, 05652-900

Hospital Santa Marcelina

Sao Paulo, Brazil, 08270-070

Canada, Ontario

Royal Victoria Regional Health Centre

Barrie, Ontario, Canada, L4M 6M2

William Osler Health Centre

Brampton, Ontario, Canada, L6W 3J7

Princess Margaret Hospital

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

McGill University Health Center

Montreal, Quebec, Canada, H4A 3J1

Chile

Hospital Amaral Carvalho

Temuco, Araucanía, Chile, 4800827

Instituto Nacional Del Cancer

Santiago, Chile, 8380455

Centro Internacional de Estudios Clinicos

Santiago, Chile

Centro de Investigaciones Clinicas Vina del Mar

Vina Del Mar, Chile, 2570017

China, Jiangsu

Hospital de Clinicas de Passo Fundo

Nanjing, Jiangsu, China, 210029

China, Shanghai

Ruijin Hospital Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai, China, 200025

China, Zhejiang

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China, 310003

China

Beijing Chaoyang Hospital Capital Medical University

Beijing, China, 100020

Peking University Third Hospital

Beijing, China, 100191

Peking Union Medical College Hospital

Beijing, China

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, China, 310003

Renji Hospital Shanghai Jiaotong University School of Medicine

Shanghai, China, 200001

Shanghai Chang Zheng Hospital

Shanghai, China, 200003

Hospital São Rafael

Shenyang, China, 110004

Second Hospital of Shanxi Medical University

Taiyuan, China, 030001

James Lind Centro de Investigación del Cáncer

Wuhan, China, 430030

Colombia

Hospital Pablo Tobon Uribe

Medellin, Antioquia, Colombia, 050034

Instituto Nacional de Cancerologia Colombia

Bogota, Cundinamarca, Colombia

Hospital Universitario San Ignacio

Bogota, Distrito Capital De Bogota, Colombia, 110311

Croatia

Clinical Hospital Dubrava

Zagreb, Grad Zagreb, Croatia, 10000

Clinical Hospital Center Rijeka

Rijeka, Croatia, 51000

Clinical Hospital Center Zagreb - PPDS

Zagreb, Croatia, 10 000

Czechia

Fakultni nemocnice Hradec Kralove

Hradec Kralove, Kralovehradeck Kraj, Czechia, 500 05

Fakultni nemocnice Kralovske Vinohrady

Prague, Praha, Hlavni Mesto, Czechia, 100 34

Fakultni nemocnice Brno

Brno, Czechia, 625 00

Fakultni nemocnice Olomouc

Olomouc, Czechia, 775 20

Fakultni nemocnice Ostrava

Ostrava, Czechia, 708 52

Vseobecna fakultni nemocnice v Praze

Praha 2, Czechia, 128 08

Denmark

Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)

København, Capital, Denmark, 2100

Aarhus Universitetshospital Århus Sygehus

Aarhus N, Denmark, DK-8200

Regionshospitalet Holstebro

Holstebro, Denmark, 7500

Odense Universitetshospital

Odense, Denmark, 5000

France

Hopital Antoine Beclere

Clamart, Hauts-de-Seine, France, 92140

Hotel Dieu

Nantes, Loire-Atlantique, France, 44093

CHRU Nancy

Vandoeuvre-les-nancy, Meurthe-et-Moselle, France, 54511

CHRU Dijon Complexe Du Bocage

Dijon, France, 21079

Hopital Saint Vincent de Paul GHICL

Lille, France, 59020

CHRU Lille

Lille, France, 59037

Hopital de la Pitie Salpetriere

Paris, France, 75013

Groupe Hospitalier Necker Enfants Malades

Paris, France, 75015

Hopital Haut Leveque

Pessac, France, 33604

Hopital Jean Bernard

Poitiers, France, 86021

CHRU Rennes

Rennes, France

Germany

Universitatsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany, 89081

Schwarzwald Baar Klinkum Villingen-Schwenningen GmbH

Villingen-Schwenningen, Baden-Wurttemberg, Germany, 78050

Hamatologische Onkologische Gemeinschaftspraxis Dr. Brudler, Dr. Heinrich, Dr. Bangerter

Augsburg, Bayern, Germany, 86150

Internistisch Hamatologische und Internistische Praxis

Herrsching am Ammersee, Bayern, Germany, 82211

LMU Klinikum der Universitat Munchen

Munchen, Bayern, Germany, 81377

Pius Hospital Oldenburg

Oldenburg, Niedersachsen, Germany, 26121

Universitatsklinikum Essen

Essen, Nordrhein-Westfalen, Germany, 45122

Gemeinschaftspraxis fur Hamatologie und Onkologie

Munster, Nordrhein-Westfalen, Germany, 48149

Universitatsmedizin der Johannes Gutenberg-Universitat Mainz

Mainz, Rheinland-Pfalz, Germany, 55131

Universitat Des Saarlandes

Homburg, Saarland, Germany, 66421

Onkologie Aschaffenburg

Aschaffenburg, Germany, 63739

Charite - Universitatsmedizin Berlin

Berlin, Germany, 12200

Medizinisches Versorgungszentrum Onkologischer Schwerpunkt

Berlin, Germany, 14195

Klinikum Landshut

Landshut, Germany, 84034

Klinikum rechts der Isar der Technischen Universitat Munchen

Munchen, Germany, 81675

Praxis Pihusch Medizinisches Versorgungszentrum GbR

Rosenheim, Germany, 83022

Gemeinschaftspraxis Dr. med. R. Schlag & Dr. med. B. Schottker & Dr. med. J. Haas

Wurzburg, Germany, 97080

Greece

University of Athens Medical School - Regional General Hospital Alexandra

Athens, Attiki, Greece, 115 28

Evangelismos General Hospital of Athens

Athens, Greece, 10676

University General Hospital of Ioannina

Ioannina, Greece, 45500

University General Hospital of Larissa

Larissa, Greece, 41110

Theageneio Anticancer Oncology Hospital of Thessaloniki

Thessaloniki, Greece, 54007

Georgios Papanikolaou General Hospital of Thessaloniki

Thessaloniki, Greece, 57010

Hungary

Semmelweis Egyetem

Budapest, Hungary, 1083

Klinika Hematologii, Szpital Uniwersytecki Nr 2 im. Jana Biziela w Bydgoszczy

Budapest, Hungary, 1097

Debreceni Egyetem Klinikai Kozpont

Debrecen, Hungary, 4032

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, Hungary, 6725

Israel

Shamir Medical Center Assaf Harofeh

Be'er Sheva, Israel, 84101

Rigshospitalet

Beer Yaakov, Israel, 70300

Bnai Zion Medical Center

Haifa, Israel, 33394

Hadassah Medical Center - PPDS

Jerusalem, Israel, 91120

Meir Medical Center

Kfar Saba, Israel, 44281

Rabin Medical Center - PPDS

Petah Tikva, Israel, 49100

Chaim Sheba Medical Center

Ramat Gan, Israel, 52621

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 64239

Assuta Medical Centers

Tel Aviv, Israel, 69710

Baruch Padeh Poriya Medical Center

Tiberias, Israel, 15208

Italy

AORN A Cardarelli

Napoli, Campania, Italy, 80131

Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi

Bologna, Emilia-Romagna, Italy, 40138

Ospedale Infermi di Rimini

Rimini, Emilia-Romagna, Italy, 47900

IRCCS Az. Osp. Universitaria San Martino- IST

Genova, Liguria, Italy, 16132

ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN

Brescia, Lombardia, Italy, 25123

ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda

Milano, Lombardia, Italy, 20162

Ospedale Casa Sollievo Della Sofferenza IRCCS

San Giovanni Rotondo, Puglia, Italy, 71013

Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele

Catania, Sicilia, Italy, 95124

Azienda Ospedaliero Universitaria Pisana

Pisa, Toscana, Italy, 56216

Azienda Ospedaliera S Maria Di Terni

Terni, Umbria, Italy, 05100

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi

Ancona, Italy, 60126

Azienda Ospedaliera Universitaria Careggi

Firenze, Italy, 50139

Azienda Ospedaliero Universitaria di Parma

Parma, Italy, 43126

Ospedale Santa Maria Delle Croci

Ravenna, Italy, 48100

Azienda Ospedaliera Citta della Salute e della Scienza di Torino

Torino, Italy, 10126

Japan

Ogaki Municipal Hospital

Ogaki, Gihu, Japan, 503-8502

Kobe City Medical Center General Hospital

Kobe-City, Hyogo, Japan, 650-0047

Hitachi General Hospital

Hitachi, Ibaraki, Japan, 317-0077

Nara Hospital Kinki University Faculty of Medicine

Ikoma-City, Nara, Japan, 630-0293

National Hospital Organization Okayama Medical Center

Okayama-city, Okayama, Japan, 701-1192

Juntendo University Hospital

Bunkyo, Tokyo, Japan, 113-8431

Japanese Red Cross Medical Center

Shibuya-ku, Tokyo, Japan, 150-8935

National Hospital Organization Kyushu Medical Center

Fukuoka, Japan, 810-8563

Fukushima Medical University Hospital

Fukushima-City, Japan, 960-1295

National Hospital Organization Mito Medical Center

Ibaraki, Japan, 311-3193

Kurume University Hospital

Kurume, Japan, 830-0011

Shizuoka Cancer Center

Nagaizumi-chō, Japan, 4118777

Japanese Red Cross Nagoya Daiichi Hospital

Nagoya, Japan, 453-8511

Nagoya City University Hospital

Nagoya, Japan, 467-8602

Japanese Red Cross Narita Hospital

Narita-shi, Japan, 286-8523

Niigata Cancer Center Hospital

Niigata-city, Japan

Osaka Saiseikai Nakatsu Hospital

Osaka, Japan, 530-0012

National Hospital Organization Disaster Medical Center

Tachikawa, Japan, 1900014

Toyohashi Municipal Hospital

Toyohashi, Japan

Yamanashi Prefectural Central Hospital

Yamanashi, Japan, 400-8506

Korea, Republic of

National Cancer Center

Goyang-si, Gyeonggido, Korea, Republic of, 10408

Gachon University Gil Medical Center

Incheon, Korea, Republic of, 405-760

Seoul National University Hospital

Seoul, Korea, Republic of, 110-744

Severance Hospital Yonsei University Health System - PPDS

Seoul, Korea, Republic of, 120-752

Samsung Medical Center - PPDS

Seoul, Korea, Republic of, 135-710

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, Korea, Republic of, 137-701

Mexico

Centro de Investigacion Farmaceutica Especializada de Occidente, SC - PPDS

Guadalajara, Jalisco, Mexico, 44160

Hospital Y Clinica OCA Sociedad Anonima de Capital Variable

Monterrey, Nuevo Leon, Mexico, 64000

Hospital Universitario Dr. Jose Eleuterio Gonzalez

Monterrey, Nuevo Leon, Mexico, 64460

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, Mexico, 14000

Oaxaca Site management Organization (OSMO) - PPDS

Oaxaca, Mexico, 68000

Poland

Shengjing Hospital of China Medical University

Bydgoszcz, Kujawsko-pomorskie, Poland, 85-168

MTZ Clinical Research Sp z o o - PRATIA - PPDS

Warszawa, Mazowieckie, Poland, 02-106

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich

Chorzow, Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu

Wroclaw, Poland, 50-367

Portugal

Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.

Lisbon, Lisboa, Portugal, 1099-023

Hospital Garcia de Orta

Almada, Portugal, 2801-951

Hospital de Braga

Braga, Portugal, 4710-243

Champalimaud Cancer Center

Lisboa, Portugal, 1400-038

Centro Hospitalar do Porto - Hospital de Santo Antonio

Porto, Portugal, 4099-001

Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS

Porto, Portugal, 4200-072

Centro Hospitalar de Sao Joao EPE

Porto, Portugal, 4200-319

Russian Federation

State Medical and Preventive Treatment Institution Kirov Regional Clinical Oncology Dispensary

Kirov, Russian Federation, 610027

Stavropol Regional Clinical Oncology Centre Pyatigorsk Affiliate

Pyatigorsk, Russian Federation, 357500

Ryazan Regional Clinical Hospital

Ryazan, Russian Federation, 390039

Russian Research Institute of Hematology and Blood Transfusion

St. Petersburg, Russian Federation, 193024

City Center of MS Treatment based on Saint-Petersburg City Clinical Hospital #31

St. Petersburg, Russian Federation, 197110

Serbia

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Belgrade, Serbia, 11000

Clinical Hospital Center ''Bezanijska Kosa''

Belgrade, Serbia, 11080

University Clinical Center Kragujevac

Kragujevac, Serbia, 34000

Soroka University Medical Centre

Nis, Serbia, 18000

Singapore

National University Hospital

Singapore, Singapore, 119074

Singapore General Hospital (SGH)

Singapore, Singapore, 169608

South Africa

Medical Oncology Centre of Rosebank

Johannesburg, Gauteng, South Africa, 2196

Albert Alberts Stem Cell Transplant Centre

Pretoria, Gauteng, South Africa, 0044

Mary Potter Oncology Centre

Pretoria, Gauteng, South Africa, 0181

Spain

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, Spain, 08916

Hospital Universitario Quironsalud Madrid

Pozuelo De Alarcon, Madrid, Communidad Delaware, Spain, 28223

Clinica Universidad Navarra

Pamplona, Navarra, Spain, 31008

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

Hospital de La Santa Creu i Sant Pau

Barcelona, Spain, 08041

Hospital Universitario de La Princesa

Madrid, Spain, 28006

Hospital General Universitario Gregorio Maranon

Madrid, Spain, 28009

Hospital Universitario Infanta Leonor

Madrid, Spain, 28031

Hospital Universitario La Paz

Madrid, Spain, 28046

Hospital Universitario HM Sanchinarro CIOCC

Madrid, Spain, 28050

Hospital General Universitario Morales Meseguer

Murcia, Spain, 30008

Complejo Asistencial Universitario de Salamanca H. Clinico

Salamanca, Spain, 37007

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, Spain, 46026

Sweden

Karolinska Universitetssjukhuset Huddinge

Stockholm, Sodermanlands Lan, Sweden

Karolinska Universitetssjukhuset Solna

Stockholm, Sodermanlands Lan, Sweden

Sahlgrenska Universitetssjukhuset

Goteborg, Vastra Gotalands Lan, Sweden

Skanes Universitetssjukhus Lund

Lund, Sweden, SE-22185

Switzerland

Spital STS AG

Thun, Switzerland, CH-3600

Taiwan

Kaohsiung Medical University Hospital

Kaohsiung, Taiwan, 807

Taichung Veterans General Hospital

Taichung, Taiwan, 40705

National Taiwan University Hospital

Taipei, Taiwan, 100

Thailand

Ramathibodi Hospital

Bangkok, Krung Thep Maha Nakhon, Thailand, 10400

Chulalongkorn University

Bangkok, Thailand, 10330

Maharaj Nakorn Chiang Mai Chiang Mai University

Chiangmai, Thailand, 50200

Turkey

Hacettepe Universitesi Tip Fakultesi Hastanesi

Ankara, Turkey, 06100

Ankara University Medical Faculty PPDS

Ankara, Turkey, 06590

Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi

Istanbul, Turkey, 34093

Dokuz Eylul University Medical Faculty

Izmir, Turkey, 35340

United Kingdom

Belfast City Hospital

Belfast, Antrim, United Kingdom, BT9 7AB

Birmingham Heartlands Hospital

West Malling, Birmingham, United Kingdom, B9 5SS

Bristol Haematology and Oncology Centre

Bristol, Bristol, City Of, United Kingdom, BS2 8ED

Royal Bournemouth Hospital

Bournemouth, Dorset, United Kingdom, BH7 7DW

Queen Alexandra Hospital

Portsmouth, Hampshire, United Kingdom, PO6 3LY

Kent and Canterbury Hospital

Canterbury, Kent, United Kingdom, CT1 3NG

Barts Health NHS Trust

London, London, City Of, United Kingdom, EC1A 7BE

University College London

London, London, City Of, United Kingdom, NW1 2BU

Kings College Hospital

London, London, City Of, United Kingdom, SE5 9RS

Hammersmith Hospital

London, London, City Of, United Kingdom, W12 0HS

Hillingdon Hospital

Uxbridge, London, City Of, United Kingdom, UB8 3NN

Churchill Hospital

Oxford, Oxfordshire, United Kingdom, OX3 7LJ

New Cross Hospital

Wolverhampton, Staffordshire, United Kingdom, WV10 0QP

Royal Marsden Hospital - Surrey

Sutton, Surrey, United Kingdom, SM2 5PT

Royal United Hospital

Bath, United Kingdom, BA1 3NG

Ulster Hospital

Belfast, United Kingdom, BT16 1RH

Southmead Hospital

Bristol, United Kingdom, BS10 5NB

University Clinical Center Nis

Cardiff, United Kingdom, CF14 4XW

West Middlesex University Hospital

Isleworth, United Kingdom, TW7 6AF

Leicester Royal Infirmary

Leicester, United Kingdom, LE1 5WW

Chelsea and Westminster NHS Trust

London, United Kingdom

Manchester Royal Infirmary - PPDS

Manchester, United Kingdom, M13 9WL

Northwick Park Hospital

Middlesex, United Kingdom, HA1 3UJ

The Royal Oldham Hospital - PPDS

Oldham, United Kingdom, OL1 2JH

University Clinical Center of Serbia - PPDS

Southall, United Kingdom, UB1 3HW

Singleton Hospital - PPDS

Swansea, United Kingdom

Sponsors and Collaborators

Takeda

Investigators

• Study Director: Study Director; Takeda

  Study Documents (Full-Text)

Documents provided by Takeda:

Study Protocol  [PDF] September 28, 2018

Statistical Analysis Plan  [PDF] September 20, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dimopoulos MA, Spicka I, Quach H, Oriol A, Hajek R, Garg M, Beksac M, Bringhen S, Katodritou E, Chng WJ, Leleu X, Iida S, Mateos MV, Morgan G, Vorog A, Labotka R, Wang B, Palumbo A, Lonial S; TOURMALINE-MM4 study group. Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial. J Clin Oncol. 2020 Dec 1;38(34):4030-4041. doi: 10.1200/JCO.20.02060. Epub 2020 Oct 6. Erratum In: J Clin Oncol. 2022 Mar 10;40(8):919.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02312258
• Other Study ID Numbers: C16021; U1111-1160-1702 ( Registry Identifier: WHO ); 2014-001394-13 ( EudraCT Number ); REec-2015-1414 ( Registry Identifier: REec ); JapicCTI-152873 ( Registry Identifier: JapicCTI ); 153300410A0048 ( Registry Identifier: RNEC ); 1046003327 ( Registry Identifier: TCTIN ); SNCTP000001745 ( Registry Identifier: SNCTP ); 15/NE/0167 ( Registry Identifier: NRES ); 182602 ( Registry Identifier: HC-CTD ); MOH_2017-06-15_000529 ( Other Identifier: CRS )
• First Posted: December 9, 2014
• Results First Posted: November 10, 2020
• Last Update Posted: January 18, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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
• URL: https://vivli.org/ourmember/takeda/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda:

Drug Therapy

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Ixazomib; Antineoplastic Agents; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action