Multiple MyelomaPhase 3NCT02312258
A Study of Oral Ixazomib Maintenance Therapy in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Not Treated With Stem Cell Transplantation (SCT)
A Phase 3 study testing Ixazomib in people with Multiple Myeloma, run by Takeda at 275 sites in 35 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Ixazomib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 706 participants
- Where
- 275 sitesin 35 countries
- Study dates
- 9 Apr 2015to 26 Aug 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic newly diagnosed multiple myeloma (NDMM) according to standard criteria.
- 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.
- Documented major response (PR, VGPR, CR) according to the International Myeloma Working Group (IMWG) uniform response criteria, version 2011, after this initial therapy.
- Female participants who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
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- 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.)
- 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.
- Complete documentation of the details of the initial therapy before randomization including cytogenetics and International Staging System (ISS) is available.
- Eastern Cooperative Oncology Group Performance Status of 0 to 2.
- Suitable venous access for the study-required blood sampling and consent for the specific amounts that will be taken.
- Is willing and able to adhere to the study visit schedule and other protocol requirements including blood sampling and bone marrow aspiration.
- 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).
Who cannot join
- Multiple myeloma that has relapsed after, or was not responsive to, initial therapy.
- Prior SCT.
- Radiotherapy within 14 days before randomization.
- 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.
- Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
- Major surgery within 14 days before randomization.
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- Central nervous system involvement.
- Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before randomization.
- 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.
- 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.
- 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.
- Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active hepatitis B or C infection.
- 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).
- Psychiatric illness or social situation that would limit compliance with study requirements.
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment.
- Treatment with any investigational products within 30 days before randomization.
Trial locations and contacts
275 sites in 35 countries.
275 sites in 35 countries
Brazil28 sites
Fundacao PIO XII
Barretos, São Paulo, 14784-400
Hospital Das Clinicas Da UFMG
Belo Horizonte, Minas Gerais, 30130-100
Universidade Estadual de Campinas
Campinas, São Paulo, 13083-878
Universidade de Caxias do Sul
Caxias do Sul, Rio Grande do Sul, 95070-560
Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner
Curitiba, Paraná, 81520-060
Hospital Das Clinicas Da Universidade Federal de Goias
Goiânia, Goiás, 74605-020
Associacao Hospital de Caridade Ijui
Ijuí, Rio Grande do Sul, 98700-000
Hospital Amaral Carvalho
Jaú, São Paulo, 17210-120
Instituto Joinvilense de Hematologia E Oncologia
Joinville, Santa Catarina, 89201260
Liga Norte Riograndense Contra O Cancer
Natal, Rio Grande do Norte, 59040-150
American Oncology Partners of Maryland, PA
Passo Fundo, Rio Grande do Sul, 99010-260
Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90035-001
Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
Porto Alegre, Rio Grande do Sul, 90035-903
Mae de Deus Center Hospital Giovanni Battista
Porto Alegre, Rio Grande do Sul, 90470-340
Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
Porto Alegre, Rio Grande do Sul, 90610-000
HEMORIO - Unidade de Pesquisa Clinica
Rio de Janeiro, 20211-030
Instituto Nacional de Cancer
Rio de Janeiro, 20231-050
Fundação Antônio Prudente - AC Camargo Câncer Center
Rio de Janeiro, 21941-913
Del-pesti Centrumkorhaz- Orszagos Hematologiai és Infektologiai Intezet
Salvador, Estado de Bahia, 41253-196
Faculdade de Medicina Do ABC
Santo André, São Paulo, 09060-650
Hospital de Base Da Faculdade de Medicina de Sao Jose Do Rio Preto
São José do Rio Preto, 15090-000
Instituto de Ensino E Pesquisa Sao Lucas
São Paulo, 01236-030
Hospital Sirio Libanes
São Paulo, 01308-050
Ealing Hospital
São Paulo, 01509-900
Clinica Sao Germano
São Paulo, 04537-080
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
São Paulo, 05403-000
Hospital Israelita Albert Einstein
São Paulo, 05652-900
Hospital Santa Marcelina
São Paulo, 08270-070
United Kingdom26 sites
Royal United Hospital
Bath, BA1 3NG
Belfast City Hospital
Belfast, Antrim, BT9 7AB
Ulster Hospital
Belfast, BT16 1RH
Royal Bournemouth Hospital
Bournemouth, Dorset, BH7 7DW
Bristol Haematology and Oncology Centre
Bristol, Bristol, City of, BS2 8ED
Southmead Hospital
Bristol, BS10 5NB
Kent and Canterbury Hospital
Canterbury, Kent, CT1 3NG
University Clinical Center Nis
Cardiff, CF14 4XW
West Middlesex University Hospital
Isleworth, TW7 6AF
Leicester Royal Infirmary
Leicester, LE1 5WW
Barts Health NHS Trust
London, London, City of, EC1A 7BE
University College London
London, London, City of, NW1 2BU
Kings College Hospital
London, London, City of, SE5 9RS
Hammersmith Hospital
London, London, City of, W12 0HS
Chelsea and Westminster NHS Trust
London
Manchester Royal Infirmary - PPDS
Manchester, M13 9WL
Northwick Park Hospital
Middlesex, HA1 3UJ
The Royal Oldham Hospital - PPDS
Oldham, OL1 2JH
Churchill Hospital
Oxford, Oxfordshire, OX3 7LJ
Queen Alexandra Hospital
Portsmouth, Hampshire, PO6 3LY
University Clinical Center of Serbia - PPDS
Southall, UB1 3HW
Royal Marsden Hospital - Surrey
Sutton, Surrey, SM2 5PT
Singleton Hospital - PPDS
Swansea
Hillingdon Hospital
Uxbridge, London, City of, UB8 3NN
Birmingham Heartlands Hospital
West Malling, Birmingham, B9 5SS
New Cross Hospital
Wolverhampton, Staffordshire, WV10 0QP
United States23 sites
Cancer Care of WNC PA
Asheville, North Carolina, 28801
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
Saint Agnes Hospital - Baltimore - Hunt - PPDS
Baltimore, Maryland, 21229
University Hospital of Wales -
Bethesda, Maryland, 20817
Tufts Medical Center - PPDS
Boston, Massachusetts, 02111
John H. Stroger Jr. Hospital of Cook County
Chicago, Illinois, 60612
Robert A Moss MD FACP Inc
Fountain Valley, California, 92708
Appalachian Regional Healthcare
Hazard, Kentucky, 41701
Herbert-Herman Cancer Center
Lansing, Michigan, 48912
UCLA Medical Hematology and Oncology
Los Angeles, California, 90095
W VA University Mary Babb Randolph Cancer Center
Morgantown, West Virginia, 26506
Clinical Research Alliance Inc
New York, New York, 10021
New York Presbyterian Hospital - Weill-Cornell
New York, New York, 10021
North County Oncology Medical Clinic Inc
Oceanside, California, 92056
Ventura County Hematology Oncology Specialists
Oxnard, California, 93030
UPMC Cancer Pavillion
Pittsburgh, Pennsylvania, 15232
Emad Ibrahim, MD, Inc
Redlands, California, 92373
Global Cancer Research Institute (GCRI), Inc.
San Jose, California, 95124
Central Coast Medical Oncology Corporation
Santa Maria, California, 93454
New England Cancer Specialists
Scarborough, Maine, 04074
Swedish Cancer Institute
Seattle, Washington, 98109
Siouxland Hematology - Oncology Associates LLP
Sioux City, Iowa, 51101
HOPE Cancer Center of East Texas
Tyler, Texas, 75701
Japan20 sites
Juntendo University Hospital
Bunkyo, Tokyo, 113-8431
National Hospital Organization Kyushu Medical Center
Fukuoka, 810-8563
Fukushima Medical University Hospital
Fukushima, 960-1295
Hitachi General Hospital
Hitachi, Ibaraki, 317-0077
National Hospital Organization Mito Medical Center
Ibaraki, 311-3193
Nara Hospital Kinki University Faculty of Medicine
Ikoma, Nara, 630-0293
Kobe City Medical Center General Hospital
Kobe, Hyōgo, 650-0047
Kurume University Hospital
Kurume, 830-0011
Shizuoka Cancer Center
Nagaizumi-chō, 4118777
Japanese Red Cross Nagoya Daiichi Hospital
Nagoya, 453-8511
Nagoya City University Hospital
Nagoya, 467-8602
Japanese Red Cross Narita Hospital
Narita-shi, 286-8523
Niigata Cancer Center Hospital
Niigata
Ogaki Municipal Hospital
Ōgaki, Gihu, 503-8502
National Hospital Organization Okayama Medical Center
Okayama, Okayama-ken, 701-1192
Osaka Saiseikai Nakatsu Hospital
Osaka, 530-0012
Japanese Red Cross Medical Center
Shibuya-ku, Tokyo, 150-8935
National Hospital Organization Disaster Medical Center
Tachikawa, 1900014
Toyohashi Municipal Hospital
Toyohashi
Yamanashi Prefectural Central Hospital
Yamanashi, 400-8506
Germany17 sites
Onkologie Aschaffenburg
Aschaffenburg, 63739
Hamatologische Onkologische Gemeinschaftspraxis Dr. Brudler, Dr. Heinrich, Dr. Bangerter
Augsburg, Bavaria, 86150
Charite - Universitatsmedizin Berlin
Berlin, 12200
Medizinisches Versorgungszentrum Onkologischer Schwerpunkt
Berlin, 14195
Universitatsklinikum Essen
Essen, North Rhine-Westphalia, 45122
Internistisch Hamatologische und Internistische Praxis
Herrsching am Ammersee, Bavaria, 82211
Universitat Des Saarlandes
Homburg, Saarland, 66421
Klinikum Landshut
Landshut, 84034
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz
Mainz, Rhineland-Palatinate, 55131
LMU Klinikum der Universitat Munchen
München, Bavaria, 81377
Klinikum rechts der Isar der Technischen Universitat Munchen
München, 81675
Gemeinschaftspraxis fur Hamatologie und Onkologie
Münster, North Rhine-Westphalia, 48149
Pius Hospital Oldenburg
Oldenburg, Lower Saxony, 26121
Praxis Pihusch Medizinisches Versorgungszentrum GbR
Rosenheim, 83022
Universitatsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081
Schwarzwald Baar Klinkum Villingen-Schwenningen GmbH
Villingen-Schwenningen, Baden-Wurttemberg, 78050
Gemeinschaftspraxis Dr. med. R. Schlag & Dr. med. B. Schottker & Dr. med. J. Haas
Würzburg, 97080
Italy15 sites
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
Ancona, 60126
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
Bologna, Emilia-Romagna, 40138
ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN
Brescia, Lombardy, 25123
Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele
Catania, Sicily, 95124
Azienda Ospedaliera Universitaria Careggi
Florence, 50139
IRCCS Az. Osp. Universitaria San Martino- IST
Genoa, Liguria, 16132
ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
Milan, Lombardy, 20162
AORN A Cardarelli
Naples, Campania, 80131
Azienda Ospedaliero Universitaria di Parma
Parma, 43126
Azienda Ospedaliero Universitaria Pisana
Pisa, Tuscany, 56216
Ospedale Santa Maria Delle Croci
Ravenna, 48100
Ospedale Infermi di Rimini
Rimini, Emilia-Romagna, 47900
Ospedale Casa Sollievo Della Sofferenza IRCCS
San Giovanni Rotondo, Apulia, 71013
Azienda Ospedaliera S Maria Di Terni
Terni, Umbria, 05100
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
Torino, 10126
Spain13 sites
Hospital Universitario Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Clinic de Barcelona
Barcelona, 08036
Hospital de La Santa Creu i Sant Pau
Barcelona, 08041
Hospital Universitario de La Princesa
Madrid, 28006
Hospital General Universitario Gregorio Maranon
Madrid, 28009
Hospital Universitario Infanta Leonor
Madrid, 28031
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario HM Sanchinarro CIOCC
Madrid, 28050
Hospital General Universitario Morales Meseguer
Murcia, 30008
Clinica Universidad Navarra
Pamplona, Navarre, 31008
Hospital Universitario Quironsalud Madrid
Pozuelo de Alarcón, Madrid, Communidad Delaware, 28223
Complejo Asistencial Universitario de Salamanca H. Clinico
Salamanca, 37007
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
China12 sites
Beijing Chaoyang Hospital Capital Medical University
Beijing, 100020
Peking University Third Hospital
Beijing, 100191
Peking Union Medical College Hospital
Beijing
The First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou, Zhejiang, 310003
The First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou, 310003
Hospital de Clinicas de Passo Fundo
Nanjing, Jiangsu, 210029
Ruijin Hospital Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, 200025
Renji Hospital Shanghai Jiaotong University School of Medicine
Shanghai, 200001
Shanghai Chang Zheng Hospital
Shanghai, 200003
Hospital São Rafael
Shenyang, 110004
Second Hospital of Shanxi Medical University
Taiyuan, 030001
James Lind Centro de Investigación del Cáncer
Wuhan, 430030
France11 sites
Hopital Antoine Beclere
Clamart, Hauts-de-Seine, 92140
CHRU Dijon Complexe Du Bocage
Dijon, 21079
Hopital Saint Vincent de Paul GHICL
Lille, 59020
CHRU Lille
Lille, 59037
Hotel Dieu
Nantes, Loire-Atlantique, 44093
Hopital de la Pitie Salpetriere
Paris, 75013
Groupe Hospitalier Necker Enfants Malades
Paris, 75015
Hopital Haut Leveque
Pessac, 33604
Hopital Jean Bernard
Poitiers, 86021
CHRU Rennes
Rennes
CHRU Nancy
Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54511
Israel10 sites
Rigshospitalet
Beer Yaakov, 70300
Shamir Medical Center Assaf Harofeh
Beersheba, 84101
Bnai Zion Medical Center
Haifa, 33394
Hadassah Medical Center - PPDS
Jerusalem, 91120
Meir Medical Center
Kfar Saba, 44281
Rabin Medical Center - PPDS
Petah Tikva, 49100
Chaim Sheba Medical Center
Ramat Gan, 52621
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
Assuta Medical Centers
Tel Aviv, 69710
Baruch Padeh Poriya Medical Center
Tiberias, 15208
Portugal7 sites
Hospital Garcia de Orta
Almada, 2801-951
Hospital de Braga
Braga, 4710-243
Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E.
Lisbon, Lisbon District, 1099-023
Champalimaud Cancer Center
Lisbon, 1400-038
Centro Hospitalar do Porto - Hospital de Santo Antonio
Porto, 4099-001
Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
Porto, 4200-072
Centro Hospitalar de Sao Joao EPE
Porto, 4200-319
Czechia6 sites
Fakultni nemocnice Brno
Brno, 625 00
Fakultni nemocnice Hradec Kralove
Hradec Králové, Kralovehradeck Kraj, 500 05
Fakultni nemocnice Olomouc
Olomouc, 775 20
Fakultni nemocnice Ostrava
Ostrava, 708 52
Fakultni nemocnice Kralovske Vinohrady
Prague, Praha, Hlavni Mesto, 100 34
Vseobecna fakultni nemocnice v Praze
Prague, 128 08
Greece6 sites
University of Athens Medical School - Regional General Hospital Alexandra
Athens, Attica, 115 28
Evangelismos General Hospital of Athens
Athens, 10676
University General Hospital of Ioannina
Ioannina, 45500
University General Hospital of Larissa
Larissa, 41110
Theageneio Anticancer Oncology Hospital of Thessaloniki
Thessaloniki, 54007
Georgios Papanikolaou General Hospital of Thessaloniki
Thessaloniki, 57010
South Korea6 sites
National Cancer Center
Goyang-si, Gyeonggido, 10408
Gachon University Gil Medical Center
Incheon, 405-760
Seoul National University Hospital
Seoul, 110-744
Severance Hospital Yonsei University Health System - PPDS
Seoul, 120-752
Samsung Medical Center - PPDS
Seoul, 135-710
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 137-701
Argentina5 sites
Hospital Universitario Austral
Buenos Aires, Ciudad Autonoma de BuenosAires, B1629AHJ
Hospital Italiano de Buenos Aires
Buenos Aires, Ciudad Autonoma de BuenosAires, C1181ACH
Centro de Educacion Medica e Investigaciones Clinicas "Norberto Quirno" (CEMIC)
Buenos Aires, Ciudad Autonoma de BuenosAires, C1431FWO
Sanatorio Allende S.A.
Córdoba, X5000JHQ
Hospital Iturraspe
Santa Fe, S3000ADL
Mexico5 sites
Centro de Investigacion Farmaceutica Especializada de Occidente, SC - PPDS
Guadalajara, Jalisco, 44160
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Mexico City, 14000
Hospital Y Clinica OCA Sociedad Anonima de Capital Variable
Monterrey, Nuevo León, 64000
Hospital Universitario Dr. Jose Eleuterio Gonzalez
Monterrey, Nuevo León, 64460
Oaxaca Site management Organization (OSMO) - PPDS
Oaxaca City, 68000
Russia5 sites
State Medical and Preventive Treatment Institution Kirov Regional Clinical Oncology Dispensary
Kirov, 610027
Stavropol Regional Clinical Oncology Centre Pyatigorsk Affiliate
Pyatigorsk, 357500
Ryazan Regional Clinical Hospital
Ryazan, 390039
Russian Research Institute of Hematology and Blood Transfusion
Saint Petersburg, 193024
City Center of MS Treatment based on Saint-Petersburg City Clinical Hospital #31
Saint Petersburg, 197110
Austria4 sites
Universitatsklinikum Innsbruck
Innsbruck, Tyrol, 6020
Paracelsus Medizinische Privatuniversitat
Salzburg, 5020
Medizinische Universitat Wien (Medical University of Vienna)
Vienna, A-1090
Klinikum Wels-Grieskirchen GmbH
Wels, 4600
Canada4 sites
Royal Victoria Regional Health Centre
Barrie, Ontario, L4M 6M2
William Osler Health Centre
Brampton, Ontario, L6W 3J7
McGill University Health Center
Montreal, Quebec, H4A 3J1
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
Chile4 sites
Instituto Nacional Del Cancer
Santiago, 8380455
Centro Internacional de Estudios Clinicos
Santiago
Hospital Amaral Carvalho
Temuco, Araucania, 4800827
Centro de Investigaciones Clinicas Vina del Mar
Viña del Mar, 2570017
Denmark4 sites
Aarhus Universitetshospital Århus Sygehus
Aarhus N, DK-8200
Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)
Copenhagen, Capital, 2100
Regionshospitalet Holstebro
Holstebro, 7500
Odense Universitetshospital
Odense, 5000
Hungary4 sites
Semmelweis Egyetem
Budapest, 1083
Klinika Hematologii, Szpital Uniwersytecki Nr 2 im. Jana Biziela w Bydgoszczy
Budapest, 1097
Debreceni Egyetem Klinikai Kozpont
Debrecen, 4032
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
Szeged, 6725
Poland4 sites
Shengjing Hospital of China Medical University
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-168
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
Chorzów
MTZ Clinical Research Sp z o o - PRATIA - PPDS
Warsaw, Masovian Voivodeship, 02-106
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu
Wroclaw, 50-367
Serbia4 sites
Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
Belgrade, 11000
Clinical Hospital Center ''Bezanijska Kosa''
Belgrade, 11080
University Clinical Center Kragujevac
Kragujevac, 34000
Soroka University Medical Centre
Niš, 18000
Sweden4 sites
Sahlgrenska Universitetssjukhuset
Gothenburg, Västra Götaland County
Skanes Universitetssjukhus Lund
Lund, SE-22185
Karolinska Universitetssjukhuset Huddinge
Stockholm, Södermanland County
Karolinska Universitetssjukhuset Solna
Stockholm, Södermanland County
Turkey (Türkiye)4 sites
Hacettepe Universitesi Tip Fakultesi Hastanesi
Ankara, 06100
Ankara University Medical Faculty PPDS
Ankara, 06590
Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
Istanbul, 34093
Dokuz Eylul University Medical Faculty
Izmir, 35340
Australia3 sites
St Vincents Hospital Melbourne - PPDS
Fitzroy, Victoria, 3065
Frankston Hospital
Frankston, Victoria, 3199
The Alfred Hospital
Melbourne, Victoria, 3004
Belgium3 sites
Universitair Ziekenhuis Brussel - PIN
Brussels, Brussels Capital, 1090
UZ Brussel
Brussels, Brussels Capital, 1090
Cliniques Universitaires Saint-Luc
Brussels, Brussels Capital, 1200
Colombia3 sites
Instituto Nacional de Cancerologia Colombia
Bogota, Cundinamarca
Hospital Universitario San Ignacio
Bogotá, Bogota D.C., 110311
Hospital Pablo Tobon Uribe
Medellín, Antioquia, 050034
Croatia3 sites
Clinical Hospital Center Rijeka
Rijeka, 51000
Clinical Hospital Dubrava
Zagreb, City of Zagreb, 10000
Clinical Hospital Center Zagreb - PPDS
Zagreb, 10 000
South Africa3 sites
Medical Oncology Centre of Rosebank
Johannesburg, Gauteng, 2196
Albert Alberts Stem Cell Transplant Centre
Pretoria, Gauteng, 0044
Mary Potter Oncology Centre
Pretoria, Gauteng, 0181
Taiwan3 sites
Kaohsiung Medical University Hospital
Kaohsiung City, 807
Taichung Veterans General Hospital
Taichung, 40705
National Taiwan University Hospital
Taipei, 100
Thailand3 sites
Ramathibodi Hospital
Bangkok, Bangkok, 10400
Chulalongkorn University
Bangkok, 10330
Maharaj Nakorn Chiang Mai Chiang Mai University
Chiang Mai, 50200
Singapore2 sites
National University Hospital
Singapore, 119074
Singapore General Hospital (SGH)
Singapore, 169608
About this study
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
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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- Placebo, Ixazomib
- Keywords
- Drug Therapy
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Ixazomib placebo-matching capsules.
IxazomibDrug
Ixazomib capsules.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Ixazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26. Receives: Drug: Placebo |
| Ixazomib | Experimental | Ixazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26. Receives: Drug: Ixazomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (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 is defined as, increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/ deciliter (dL)); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved free light chains (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).
Measured: From randomization until PD or death (up to 52 months)
Secondary outcomes (19)
Overall Survival (OS)
OS was measured as the time from the date of randomization to the date of death.
Measured: From the date of randomization and every 12 weeks after PD on next-line therapy until death (up to 88 months)
Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period
Response was assessed according to IMWG criteria based on IRC assessment. Best response included PR, VGPR and CR. PR= >=50% reduction of serum M protein and >=90% or <200 mg reduction urinary M protein in 24-hour, or >50% decrease in difference between involved and uninvolved FLC levels, or >50% reduction in bone marrow plasma cells, if bone marrow plasma cells >30% and >50% reduction in size of soft tissue plasmacytomas at baseline. VGPR= >90% reduction (<100 mg/24-hour) in serum M-protein + urine M-protein detectable by immunofixation but not on electrophoresis. Complete response= >5% plasma cells in myelogram with absence of paraprotein in serum and urine according to immunofixation.
Measured: Up to 27 months
Time to Progression (TTP)
TTP is defined as the time from the date of randomization to the date of first documentation of PD, using IMWG criteria.
Measured: From randomization until PD or death (up to 52 months)
Progression Free Survival 2 (PFS2)
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 occurred first.
Measured: From the date of randomization to every 12 weeks until second PD or death (up to 88 months)
Time to Next Line Therapy (TTNT)
TTNT is defined as the time from the date of randomization to the date of the first dose of next-line antineoplastic therapy.
Measured: From randomization until PD or death (up to 52 months)
Time to End of the Next-line of Therapy After Study Treatment
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.
Measured: From randomization until PD or death (up to 52 months)
Duration of Next-line Therapy
Duration of next-line therapy is defined as the time from the date of the first dose of the next line of antineoplastic therapy coming after study treatment to the date of the last dose.
Measured: From randomization until PD or death (up to 52 months)
Percentage of Participants Who Develop a New Primary Malignancy
Measured: From randomization until PD or death (up to 52 months)
Percentage of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative
Bone marrow aspirates and blood samples were sent to a central laboratory and were assessed for MRD using flow cytometry. MRD negativity was defined as absence of MRD and MRD positivity was defined as presence of MRD. MRD was assessed by 8-color flow cytometry with the IMWG recommended sensitivity of 10^-5.
Measured: Up to 52 months
Correlation of MRD Status With PFS and OS
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 occurred first, assessed for up to 52 months in this outcome measure. OS was measured as the time from the date of randomization to the date of death, assessed for up to 52 months in this outcome measure. Participants with various types of known MRD status were pooled together for analysis of overall survival in this outcome measure.
Measured: From randomization up to 52 months
OS in a High-risk Population
High-risk population included but not be limited to participants carrying cytogenetic deletion (del)17, translocation [t](4;14), t(14;16). OS was measured as the time from the date of randomization to the date of death.
Measured: From the date of randomization and every 12 weeks after PD on next-line therapy until death (up to 88 months)
PFS in a High-risk Population
High-risk population included but not be limited to participants carrying del17, t(4;14), t(14;16). PFS was defined as the time from the date of randomization to the date of first documentation of PD or death from any cause.
Measured: From randomization until PD or death (up to 52 months)
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG performance status assesses a participant's performance status on a 6-point scale ranging from 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 (>50% 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. Lower grades indicate improvement.
Measured: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, and 26, progression free survival follow-up (PFSFU)- Visit 37 and progressive disease follow-up (PDFU)- Visit 26 (cycle length=28 days)
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAEs were defined as events that occurred after administration of the first dose of ixazomib or placebo through 30 days after the last dose of ixazomib or placebo. A SAE means any untoward medical occurrence that resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was considered medically significant.
Measured: First dose of study drug through 30 days after last dose of study drug (up to 88 months)
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS)
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The change from baseline in GHS (EORTC QLQ-C30) score is presented. Participant responses to the question "How would you rate your overall health during the past week?" are scored on a 7-point scale (1=very poor to 7=excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better overall GHS.
Measured: Baseline, Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, and 26 (cycle length=28 days)
Correlation Between Frailty Status and PFS and OS
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, assessed for up to 52 months in this outcome measure. OS will be measured as the time from the date of randomization to the date of death, assessed for up to 52 months in this outcome measure.
Measured: From randomization up to 52 months
Pharmacokinetic Parameter: Plasma Concentration of Ixazomib
Plasma concentrations of the complete hydrolysis product of ixazomib citrate (ixazomib) were measured using a validated liquid chromatography-tandem mass spectrometry (LC/MS/MS) assay.
Measured: 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 to 10 (Day 1 pre-dose) (cycle length=28 days)
Time to Resolution of Peripheral Neuropathy (PN) Events
PN is defined as the 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 was considered as resolved if its final outcome was 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 was defined as the time from the initial onset date (inclusive) to the resolution date for resolved events.
Measured: Up to 52 months
Time to Improvement of PN Events
PN is defined as the event in the high-level term of peripheral neuropathies NEC according to the MedDRA. A PN event was considered as resolved if its final outcome was 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 was defined as the time from the initial onset date (inclusive) to the improvement of event.
Measured: Up to 52 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2014 (estimated)
- Study start9 Apr 2015
- Primary completion12 Aug 2019
- Study completion26 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 706 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02312258
- Sponsor's protocol ID
- C16021
- Other IDs
- U1111-1160-1702, 2014-001394-13, REec-2015-1414, JapicCTI-152873, 153300410A0048, 1046003327, SNCTP000001745, 15/NE/0167
- Status last verified
- Aug 2023
- First submitted
- 5 Dec 2014
- Last updated
- 21 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Paiva B, Manrique I, Dimopoulos MA, Gay F, Min CK, Zweegman S, Spicka I, Teipel R, Mateos MV, Giuliani N, Cavo M, Hopkins CR, Fu W, Suryanarayan K, Vorog A, Li C, Wang B, Estevam J, Labotka R, Dash AB. MRD dynamics during maintenance for improved prognostication of 1280 patients with myeloma in the TOURMALINE-MM3 and -MM4 trials. Blood. 2023 Feb 9;141(6):579-591. doi: 10.1182/blood.2022016782.
PubMed 36130300Dimopoulos 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.
PubMed 33021870
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02312258
- Acronym / sponsor ID
- C16021
- Conditions
- Multiple Myeloma
- Keywords
- Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 706 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- 9 Apr 2015 (actual)
- Primary completion
- 12 Aug 2019 (actual)
- Study completion
- 26 Aug 2022 (actual)
- First posted
- 9 Dec 2014 (estimated)
- Results
- Posted 10 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboIxazomib placebo-matching capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 through 26. |
| Ixazomib | Experimental | Drug: IxazomibIxazomib 3 mg, capsule, orally, once on Days 1, 8, and 15 of each 28-day cycle from Cycles 1 to 4 that may have been escalated to 4 mg thereafter up to Cycle 26. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic newly diagnosed multiple myeloma (NDMM) according to standard criteria.
- 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.
- Documented major response (PR, VGPR, CR) according to the International Myeloma Working Group (IMWG) uniform response criteria, version 2011, after this initial therapy.
- Female participants who:
- 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.
Key exclusion criteria (17 listed)
- Multiple myeloma that has relapsed after, or was not responsive to, initial therapy.
- Prior SCT.
- Radiotherapy within 14 days before randomization.
- 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.
- Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboIxazomib placebo-matching capsules. | Drug | Placebo |
| IxazomibIxazomib capsules. | Drug | Ixazomib |
Primary outcome
Progression Free Survival (PFS)
Time frame: From randomization until PD or death (up to 52 months)
PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (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 is defined as, increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/ deciliter (dL)); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved free light chains (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).
19 secondary outcomes
Overall Survival (OS)
Time frame: From the date of randomization and every 12 weeks after PD on next-line therapy until death (up to 88 months)
Percentage of Participants Who Achieve or Maintain Any Best Response Category During the Treatment Period
Time frame: Up to 27 months
Time to Progression (TTP)
Time frame: From randomization until PD or death (up to 52 months)
Progression Free Survival 2 (PFS2)
Time frame: From the date of randomization to every 12 weeks until second PD or death (up to 88 months)
Time to Next Line Therapy (TTNT)
Time frame: From randomization until PD or death (up to 52 months)
Time to End of the Next-line of Therapy After Study Treatment
Time frame: From randomization until PD or death (up to 52 months)
Duration of Next-line Therapy
Time frame: From randomization until PD or death (up to 52 months)
Percentage of Participants Who Develop a New Primary Malignancy
Time frame: From randomization until PD or death (up to 52 months)
Percentage of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative
Time frame: Up to 52 months
Correlation of MRD Status With PFS and OS
Time frame: From randomization up to 52 months
OS in a High-risk Population
Time frame: From the date of randomization and every 12 weeks after PD on next-line therapy until death (up to 88 months)
PFS in a High-risk Population
Time frame: From randomization until PD or death (up to 52 months)
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Time frame: Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, and 26, progression free survival follow-up (PFSFU)- Visit 37 and progressive disease follow-up (PDFU)- Visit 26 (cycle length=28 days)
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: First dose of study drug through 30 days after last dose of study drug (up to 88 months)
Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) as Measured by the Global Health Status (GHS)
Time frame: Baseline, Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, and 26 (cycle length=28 days)
Correlation Between Frailty Status and PFS and OS
Time frame: From randomization up to 52 months
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 to 10 (Day 1 pre-dose) (cycle length=28 days)
Time to Resolution of Peripheral Neuropathy (PN) Events
Time frame: Up to 52 months
Time to Improvement of PN Events
Time frame: Up to 52 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36130300Paiva B, Manrique I, Dimopoulos MA, Gay F, Min CK, Zweegman S, Spicka I, Teipel R, Mateos MV, Giuliani N, Cavo M, Hopkins CR, Fu W, Suryanarayan K, Vorog A, Li C, Wang B, Estevam J, Labotka R, Dash AB. MRD dynamics during maintenance for improved prognostication of 1280 patients with myeloma in the TOURMALINE-MM3 and -MM4 trials. Blood. 2023 Feb 9;141(6):579-591. doi: 10.1182/blood.2022016782.
- Derived from this study: PubMed 33021870Dimopoulos 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Takeda
275 sites in 35 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ixazomib in people with Multiple Myeloma, run by Takeda at 275 sites in 35 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 275 sites in Brazil, United Kingdom, United States, Japan, Germany and 30 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: From randomization until PD or death (up to 52 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02312258, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.