A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Participants With Multiple Myeloma Following Autologous Stem Cell Transplant

Multiple Myeloma Clinical Trial

Official title:

A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Patients With Multiple Myeloma Following Autologous Stem Cell Transplant

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02181413
• Other study ID #: C16019
• Secondary ID: U1111-1155-86952
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 1, 2014
• Est. completion date: July 31, 2024

Study information

• Verified date: August 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the effect of ixazomib citrate maintenance therapy on progression-free survival (PFS), compared to placebo, in participants with newly diagnosed multiple myeloma (NDMM) who have had a response (complete response [CR], very good partial response [VGPR], or partial response [PR]) to induction therapy followed by high-dose therapy (HDT) and autologous stem cell transplant (ASCT).

Description:

The investigational drug being tested in this study is called ixazomib citrate. Ixazomib citrate is being tested to slow disease progression and improve overall survival in people who have NDMM and who have had any type of positive response to induction therapy followed by HDT and ASCT. This study will look at the effect ixazomib citrate has on the length of time that participants are free of progressive disease (PD) and their overall survival (OS).

The study enrolled 656 participants. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need, or if the disease has progressed and the information is required for planning the next treatment):

• Ixazomib citrate 3 mg for the first 4 cycles, then 4 mg for the remaining 22 cycles

• 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, for up to 26 cycles (approximately 24 months).

This multi-center trial will be conducted globally. The overall time to participate in this study is up to 107 months. Participants will make 28 visits to the clinic during the treatment period and will continue to make visits after treatment has ended. During this initial follow up period, participants will be assessed for disease status with follow up every 12 weeks. After the next line of therapy begins, follow-up will occur every 12 weeks until death or termination of the study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 656
• Est. completion date: July 31, 2024
• Est. primary completion date: April 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic multiple myeloma according to standard criteria.

2. Documented results of cytogenetics/ fluorescence in situ hybridization (FISH) obtained at any time before transplant, and International Staging System (ISS) staging at the time of diagnosis available.

3. Underwent standard of care (SOC) induction therapy (induction therapy must include proteasome inhibitor (PI) and/or immunomodulating drugs (IMiD)-based regimens as primary therapy for multiple myeloma), followed by a single autologous stem cell transplant (ASCT) with a high-dose melphalan (200 mg/m^2) conditioning regimen, within 12 months of diagnosis. Vincristine, Adriamycin [doxorubicin], and dexamethasone (VAD) is not an acceptable induction therapy for this trial.

4. Started screening no earlier than 75 days after transplant, completed screening within 15 days, and randomized no later than 115 days after transplant.

5. Must have not received post-ASCT consolidation therapy.

6. Documented response to ASCT (PR, VGPR, CR/stringent complete response [sCR]) according to IMWG criteria.

7. ECOG performance status of 0 to 2.

8. Female participants who:

• 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, AND

• Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, 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 for the female partner] and withdrawal are not acceptable methods of contraception.) Male participants, even if surgically sterilized (ie, 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, AND

• Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, 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 for the female partner] and withdrawal are not acceptable methods of contraception.)

9. 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.

10. Suitable venous access for the study-required blood sampling.

11. Is willing and able to adhere to the study visit schedule and other protocol requirements.

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

• Absolute neutrophil count (ANC) = 1,000 per cubic milliliter (/mm^3) 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 = 1.5 * the upper limit of the normal range (ULN).

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 * ULN.

• Calculated creatinine clearance = 30 milliliter per minute (mL/min).

Exclusion Criteria:

1. Multiple myeloma that has relapsed following primary therapy or is not responsive to primary therapy. For this study, stable disease following ASCT will be considered nonresponsive to primary therapy.

2. Double (tandem) ASCT.

3. Radiotherapy within 14 days before the first dose of study drug.

4. Diagnosed or treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy with evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

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, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.

10. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic 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 use of Ginkgo biloba or St. John's wort within 14 days before randomization in the study.

12. Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.

13. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (eg, peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause).

14. Psychiatric illness/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 60 days before the first dose of the study drug regimen.

Related Conditions & MeSH terms

• Autologous Stem Cell Transplant
• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Ixazomib Citrate
Ixazomib citrate capsules
• Placebo
Ixazomib citrate placebo-matching capsules

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires
Argentina	Hospital Italiano de La Plata	La Plata	Buenos Aires
Argentina	Instituto de Hematologia Y Medicina Clinica Dr Ruben Davoli	Rosario	Santa Fe
Argentina	Sanatorio Britanico de Rosario	Rosario	Santa Fe
Argentina	Sanatorio Parque de Rosario	Rosario	Santa Fe
Argentina	Hospital Iturraspe	Santa Fe
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Austin Health	Heidelberg	Victoria
Australia	St George Hospital	Kogarah	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Icon Cancer Care South Brisbane	South Brisbane	Queensland
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Austria	Elisabethinen Hospital Linz	Linz
Austria	Salzburger Landeskliniken	Salzburg
Austria	Allgemeines Krankenhaus der Stadt Wien	Wien
Austria	Klinik Ottakring (fruher: Wilhelminenspital)	Wien
Belgium	ZNA Middelheim	Antwerpen
Belgium	ZNA Stuivenberg	Antwerpen
Belgium	AZ Sint-Jan AV	Brugge	West-Vlaanderen
Belgium	UZ Gent	Gent	Oost-Vlaanderen
Belgium	Centre Hospitalier Jolimont-Lobbes	La Louviere	Hainaut
Belgium	Centre Hospitalier Universitaire Ambroise Pare	Mons	Hainaut
Brazil	Hospital Das Clinicas Da Universidade Federal de Minas Gerais	Belo Horizonte	Minas Gerais
Brazil	Instituto de Oncologia Do Parana	Curitiba	Parana
Brazil	Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner	Curitiba	Parana
Brazil	Centro de Pesquisas Oncologicas	Florianopolis	Santa Catarina
Brazil	Hospital Amaral Carvalho	Jau	Sao Paulo
Brazil	Instituto Joinvilense de Hematologia E Oncologia	Joinville	Santa Catarina
Brazil	Hospital de Clinicas de Passo Fundo	Passo Fundo	Rio Grande Do Sul
Brazil	Hospital de Clinicas de Porto Alegre (HCPA) - PPDS	Porto Alegre	Rio Grande Do Sul
Brazil	Mae de Deus Center Hospital Giovanni Battista	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Nacional de Cancer	Rio De Janeiro
Brazil	Universidade Federal do Rio de Janeiro - UFRJ	Rio de Janeiro
Brazil	Hospital de Base Da FAMERP	Sao Jose Do Rio Preto	Sao Paulo
Brazil	Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo	Sao Paulo
Brazil	Hospital Israelita Albert Einstein	Sao Paulo
Brazil	Irmandade Da Santa Casa de Misericordia de Sao Paulo	Sao Paulo
Canada	MUHC-Glen Site	Montreal	Quebec
Canada	University Health Network	Toronto	Ontario
Colombia	Instituto Nacional de Cancerologia Colombia	Bogota	Cundinamarca
Colombia	Fundacion Valle Del Lili	Cali	Valle Del Cauca
Colombia	Hospital Pablo Tobon Uribe	Medellin
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove	Kralovehradeck Kraj
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha
Czechia	Vseobecna Fakultni Nemocnice V Praze	Praha 2
Denmark	Aalborg Universitetshospital	Aalborg	Nordjylland
Denmark	Aarhus Universitetshospital Arhus Sygehus	Aarhus N
Denmark	Rigshospitalet	Copenhagen
Denmark	Herlev Hospital	Herlev	Capital
Denmark	Odense Universitetshospital	Odense
Denmark	Sjallands Universitetshospital, Roskilde	Roskilde
Denmark	Vejle Sygehus	Vejle
France	Hopital Antoine Beclere	Clamart	Hauts-de-Seine
France	CHRU Lille	Lille	Nord
France	Hopital Universitaire Dupuytren	Limoges
France	Hotel Dieu - Nantes	Nantes	Loire-Atlantique
France	Groupe Hospitalier Necker Enfants Malades	Paris
Germany	Charite - Universitatsmedizin Berlin	Berlin
Germany	Helios Klinikum Berlin-Buch	Berlin
Germany	Universitatsklinikum Bonn	Bonn	Nordrhein-Westfalen
Germany	Klinikum Darmstadt GmbH	Darmstadt	Hessen
Germany	Universitatsklinikum Carl Gustav Carus an der TU Dresden	Dresden	Sachsen
Germany	Evangelisches Krankenhaus Essen Werden gGmbH	Essen	Nordrhein-Westfalen
Germany	Universitatsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Klinikum Frankfurt Hochst GmbH	Frankfurt am Main	Hessen
Germany	Katholisches Krankenhaus Hagen gGmbH	Hagen	Nordrhein-Westfalen
Germany	Asklepios Klinik Altona	Hamburg
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Universitatsklinikum Hamburg Eppendorf	Hamburg
Germany	KRH Klinikum Siloah-Oststadt-Heidehaus	Hannover
Germany	University Clinic Heidelberg	Heidelberg	Baden-Wurttemberg
Germany	Uniklinik Koln	Koln	Nordrhein-Westfalen
Germany	Klinikum der Stadt Ludwigshafen gGmbH	Ludwigshafen
Germany	Universitatsmedizin der Johannes Gutenberg-Universitat Mainz	Mainz	Rheinland-Pfalz
Germany	Klinikum Mannheim Universitatsklinikum gGmbH	Mannheim	Baden-Wurttemberg
Germany	LMU Klinikum der Universitat Munchen	Munchen	Bayern
Germany	Pius Hospital Oldenburg	Oldenburg	Niedersachsen
Germany	Universitatsklinikum Tubingen	Tubingen
Germany	Universitatsklinikum Ulm	Ulm	Baden-Wurttemberg
Germany	Universitatsklinikum Wurzburg	Wurzburg	Bayern
Greece	Alexandra Hospital	Athens
Greece	Evangelismos General Hospital of Athens	Athens	Attiki
Greece	Laiko General Hospital of Athens	Athens	Attiki
Greece	Georgios Papanikolaou General Hospital of Thessaloniki	Thessaloniki
Hungary	Del-pesti Centrumkorhaz- Orszagos Hematologiai es Infektologiai Intezet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz	Kaposvar
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged
Israel	Barzilai Medical Center	Ashkelon
Israel	Soroka University Medical Centre	Be'er Sheva
Israel	Bnai Zion Medical Center	Haifa
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Rambam Medical Center - PPDS	Haifa
Israel	Hadassah Medical Center PPDS -	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Galilee Medical Center	Nahariya
Israel	Rabin Medical Center - PPDS	Petach Tikva
Israel	Sheba Medical Center - PPDS	Ramat-Gan
Israel	Kaplan Medical Center	Rehovot
Israel	ZIV Medical Center	Safed
Israel	Tel Aviv Sourasky Medical Center PPDS	Tel Aviv
Israel	Shamir Medical Center Assaf Harofeh	Tzrifin
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi	Ancona	Marche
Italy	Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi	Bologna
Italy	ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN	Brescia
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	IRCCS Az. Osp. Universitaria San Martino- IST	Genova
Italy	Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l - PPDS	Meldola
Italy	ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda	Milano
Italy	Fondazione IRCCS Policlinico San Matteo di Pavia	Pavia	Lombardia
Italy	Presidio Ospedaliero di Pescara	Pescara	Abruzzo
Italy	Ospedale Infermi di Rimini	Rimini
Italy	IRCCS Centro Di Riferimento Oncologico Della Basilicata	Rionero In Vulture	Potenza
Italy	Azienda Ospedaliera San Camillo Forlanini	Roma	Lazio
Italy	Azienda Ospedaliera S Maria Di Terni	Terni	Umbria
Italy	Azienda Ospedaliera Citta della Salute e della Scienza di Torino	Torino	Piemonte
Japan	Juntendo University Hospital	Bunkyo	Tokyo
Japan	Chiba University Hospital	Chiba	Tokyo
Japan	Kyushu University Hospital	Fukuoka-City
Japan	Saitama Medical Center	Kawagoe-city	Saitama
Japan	Kobe City Medical Center General Hospital	Kobe-City	Hyogo
Japan	Iwate Medical University Hospital	Morioka-shi	Iwate
Japan	National Hospital Organization Nagoya Medical Center	Nagoya
Japan	Nagoya City University Hospital	Nagoya-City
Japan	Niigata Cancer Center Hospital	Niigata-shi	Niigata
Japan	National Hospital Organization Okayama Medical Center	Okayama-City	Okayama
Japan	National Hospital Organization Sendai Medical Center	Sendai	Miyagi
Japan	National Hospital Organaization Shibukawa Medical Center	Shibukawa
Japan	Japanese Red Cross Medical Center	Shibuya-ku	Tokyo
Japan	Center Hospital of the National Center for Global Health and Medicine	Shinjuku	Tokyo
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	National Hospital Organization Disaster Medical Center	Tachikawa
Japan	Toyohashi Municipal Hospital	Toyohashi-City
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	National Cancer Center	Goyang	Gyeonggido
Korea, Republic of	Gachon University Gil Medical Center Pharmacy	Incheon
Korea, Republic of	Asan Medical Center - PPDS	Seoul
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Samsung Medical Center - PPDS	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System - PPDS	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Mexico	Centro de Investigacion Farmaceutica Especializada de Occidente, SC - PPDS	Guadalajara	Jalisco
Mexico	Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo Leon
Netherlands	VU Medisch Centrum	Amsterdam	Noord-Holland
Netherlands	Albert Schweitzer Ziekenhuis	Dordrecht	Zuid-Holland
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Erasmus MC	Rotterdam
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Norway	Vestre Viken HF Sykehuset Asker Og Barum	Gjelta	Oppland
Norway	Oslo Universitetssykehus HF, Ulleval	Oslo
Norway	Stavanger Universitetssykehus	Stavanger
Norway	St. Olav's University Hospital	Trondheim	Sor-Trondelag
Poland	Szpital Specjalistyczny w Brzozowie	Brzozow
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich	Chorzow	Slaskie
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi	Lodz
Poland	Wojskowy Instytut Medyczny	Warszawa	Mazowieckie
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu	Wroclaw	Dolnoslaskie
Portugal	Hospital de Braga	Braga
Portugal	Centro Hospitalar E Universitario de Coimbra EPE	Coimbra
Portugal	Centro Hospitalar de Sao Joao, E.P.E.	Porto
Portugal	Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS	Porto
Singapore	National University Hospital	Singapore
Singapore	Singapore General Hospital (SGH)	Singapore
South Africa	Medical Oncology Centre of Rosebank	Johannesburg	Gauteng
South Africa	Albert Alberts Stem Cell Transplant Centre	Pretoria	Gauteng
South Africa	Mary Potter Oncology Centre	Pretoria	Gauteng
Spain	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	C.H. Regional Reina Sofia - PPDS	Cordoba
Spain	Institut Catala d'Oncologia Girona	Girona
Spain	Hospital General Universitario Gregorio Maranon	Madrid	Madrid, Communidad Delaware
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario HM Sanchinarro CIOCC	Madrid
Spain	Hospital Universitario La Paz - PPDS	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Madrid
Spain	Hospital General Universitario Morales Meseguer	Murcia
Spain	Clinica Universidad Navarra	Pamplona	Navarra
Spain	Complejo Asistencial Universitario de Salamanca H. Clinico	Salamanca
Spain	Hospital Universitario Virgen del Rocio - PPDS	Sevilla
Sweden	Sahlgrenska Universitetssjukhuset	Goteborg	Vastra Gotalands Lan
Sweden	Helsingborg Lasarett	Helsingborg	Skane Lan
Sweden	Skanes Universitetssjukhus Lund	Lund	Skane Lan
Sweden	Karolinska Universitetssjukhuset Huddinge	Stockholm
Sweden	Akademiska Sjukhuset I Uppsala	Uppsala
Switzerland	Universitatsspital Basel	Basel	Basel-Stadt (de)
Switzerland	Universitatsspital Zurich	Zurich	Zurich (de)
Taiwan	Chang Gung Medical Foundation-Kaoshiung Branch	Kaohsiung
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	Chang Gung Medical Foundation Chiayi Chang Gung Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital, Linkou	Taoyuan City
Thailand	Chulalongkorn University	Bangkok	Krung Thep Maha Nakhon-Bangkok
Thailand	Phramongkutklao Hospital	Bangkok	Krung Thep Maha Nakhon-Bangkok
Turkey	Ankara University Medical Faculty PPDS	Ankara
Turkey	Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi	Ankara
Turkey	Hacettepe Universitesi Tip Fakultesi Hastanesi	Ankara
Turkey	Pamukkale Universitesi Tip Fakultesi Hastanesi	Denizli
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi	Istanbul
Turkey	Erciyes Universitesi Tip Fakultesi Hastanesi	Kayseri
Turkey	Karadeniz Technical University Faculty of Medicine	Trabzon
Ukraine	MNPE Kyiv Center of Bone Marrow Transplantation of executive body of Kyiv council	Kyiv
United Kingdom	St James University Hospital	Leeds	Yorkshire
United Kingdom	University Hospitals Leicester	Leicester
United Kingdom	Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre	London	London, City Of
United Kingdom	Imperial College Healthcare NHS Trust	London	London, City Of
United Kingdom	Kings College Hospital	London	London, City Of
United Kingdom	University College London Hospitals (UCLH)	London
United Kingdom	Churchill Hospital	Oxford	Oxfordshire
United Kingdom	Royal Hallamshire Hospital	Sheffield	Yorkshire
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United Kingdom	Royal Marsden Hospital - Surrey	Sutton	Surrey
United Kingdom	Singleton Hospital - PPDS	Swansea
United States	Montefiore Medical Center	Bronx	New York
United States	Baylor University Medical Center	Dallas	Texas
United States	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Mayo Clinic - PPDS	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Colombia,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Singapore,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD), as evaluated by an independent review committee according to International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occured first. PD was defined as =25% increase from lowest value in: serum/urine M component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved free light chain (FLC) levels must be >10 mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must have been =10%; new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size increase; hypercalcemia development.	Randomization up to End of treatment (EOT) (24 months); thereafter followed up every 4 weeks until progression of disease or death (to data cutoff: approximately 4 years)
Secondary	Overall Survival (OS)	OS was measured as the time from the date of randomization to the date of death.	Baseline up to Follow up period (107 months)
Secondary	Percentage of Participants With Any Best Response Category Before PD or Subsequent Therapy	Response was assessed according to IMWG criteria. Best response includes PR, VGPR and CR. PR as per IMWG criteria is 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by greater than or equal to (>=) 90% or to less than (<) 200 milligram (mg) per 24 hours. VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. CR is negative immunofixation of serum and urine and disappearance of soft tissue plasmacytomas and <5% plasma cells in bone marrow. Stringent CR (sCR) is CR and normal FLC ratio and absence of clonal PCs by immunohistochemistry or 2- to 4-color flow cytometry.	Baseline up to EOT (24 months) and thereafter every 4 weeks until initiation of the next line of therapy (up to 107 months)
Secondary	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. PD is defined as >=25% increase from lowest value in: serum/urine M-component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels must be >10mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must be >=10%;new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development.	Baseline until PD (Month 107)
Secondary	Second Progression Free Survival (PFS2)	PFS2 is defined as the time from the date of randomization to the date of objective disease progression on next line treatment or death from any cause (whichever occurs first). PD is defined as >=25% increase from lowest value in: serum/urine M-component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels must be >10mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must be >=10%;new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development.	Baseline up to EOT (24 months); thereafter followed up every 4 weeks until initiation of next-line therapy and then every 12 weeks until second progressive disease (PD2) or death (up to Month 107)
Secondary	Time to Start of the Next Line of Therapy	Time to start of the next line of therapy was defined as the time from the date of randomization to the date of initiation dose of the next line of antineoplastic therapy following study treatment or death due to any cause, whichever occurs first.	Baseline up to start of next line of therapy (after 24 months treatment period followed by every 4 weeks PFS and PD follow up period)
Secondary	Time to End of the Next Line of Therapy	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 or death due to any cause, whichever occurs first.	Baseline up to end of next line of therapy (Month 107)
Secondary	Duration of the Next Line of Therapy	Duration of the next line of therapy is defined as the time from the date of the first dose of the next line of therapy to the date of the last dose of the next antineoplastic therapy following study treatment or death due to any cause, whichever occurs first. Duration of the next line of therapy will be analyzed on those participants who actually received the next line of therapy following the study treatment and duration would be summarized using Kaplan-Meier method. Participants who are still on treatment on the next line of therapy will be censored at last visit.	From the start of next line therapy after PD to the last dose of next line therapy (up to Month 107)
Secondary	Percentage of Participants Who Develop A New Primary Malignancy		Baseline until death or termination of the study (up to Month 107)
Secondary	Number of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative, and Maintenance of MRD Negativity	MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. The conversion rate from MRD positive to MRD negative and the maintenance of MRD negativity will be assessed and reported. Bone marrow aspirates and blood samples will be sent to a central laboratory and will be assessed for MRD using flow cytometry and a sequencing methodology.	Baseline up to EOT (24 months)
Secondary	Correlation Between MRD Status and Progression Free Survival (PFS) and Overall Survival (OS)	Degree of correlation will be determined between 2 methodologies for MRD assessment (8-color flow cytometry, next-generation sequencing and bone marrow aspirates and blood samples). Association between MRD status with PFS and OS will be evaluated independently from the methodology used for the assessment. The association between MRD status and PFS and OS will be evaluated in both study arms, and concordance between flow cytometry and sequencing readouts will be assessed.	Baseline up to Month 107
Secondary	OS Benefits in a High-Risk Population	High-risk population will include but not be limited to participants carrying deletion (del)17, t(4:14), t(14:16), amplification (ampl) 1q, del13, or del1p. OS will be measured as the time from the date of randomization to the date of death.	Randomization up to Month 107
Secondary	PFS Benefits in a High-Risk Population	High-risk population will include but not be limited to participants carrying deletion (del)17, t(4:14), t(14:16), amplification (ampl) 1q, del13, or del1p. PFS is defined as the time from the date of randomization to the date of first documentation of PD, as evaluated by an independent review committee according to IMWG criteria, or death due to any cause (whichever occurs first). PD is defined as >=25% increase from lowest value in: serum/urine M-component; participants without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels must be >10mg/dL; participants without measurable serum, urine M-protein levels and FLC levels, bone marrow plasma cell percent must be >=10%;new bone lesions/soft tissue plasmacytomas development/existing bone lesions/soft tissue plasmacytomas size rise; hypercalcaemia development.	Randomization up to Month 107
Secondary	Eastern Cooperative Oncology Group (ECOG) Performance Score	The ECOG performance is a 6-point scale used by doctors to assess how a participant's disease is progressing, how the disease affects the participant's daily life, and to determine appropriate treatment and prognosis. The scale is 0=Normal activity. Fully active, able to carry on all pre disease performance without restriction (best) to 5=Dead.	Baseline up to EOT (24 months), thereafter every 4 weeks until initiation of next line therapy
Secondary	Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) or Serious Adverse Events (SAEs)		First dose of study drug through 30 days after last dose of study drug (up to 24 months)
Secondary	Number of Participants With Markedly Abnormal Clinical Laboratory Values		Baseline through 30 days after the last dose of study drug (up to 24 months)
Secondary	Health-related Quality of Life (HRQL) Score Based on The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Quality of Life Domain	EORTC QLQ-C30 is completed by the participants. 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).	Baseline up to PD (up to Month 107)
Secondary	Plasma Concentration of Ixazomib	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.	Day 1 of Cycle 1 at multiple time points (up to 4 hours) post-dose; Days 8 and 15 of Cycle 1, Days 1 and 8 of Cycle 2, Day 1 of Cycles 3 through 10 (each cycle of 28 days) predose
Secondary	Time to Resolution of Peripheral Neuropathy (PN) Events	Peripheral neuropathy is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to Medical Dictionary for Regulatory Activities (MedDRA). A PN event is considered as improved if the event improves from the maximum grade. That is, all the grades recorded after the maximum grade is less than the maximum grade. Time to improvement is defined as the time from the initial onset date (inclusive) of the maximum grade to the first onset date that the toxicity grade is below the maximum grade with no higher grade thereafter, or the resolution date, whichever occurs first.	From randomization date through 30 days after the last dose of drug (up to 24 months)
Secondary	Time to Improvement of PN Events	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. A PN event is considered as improved if the event improves from the maximum grade. That is, all the grades recorded after the maximum grade is less than the maximum grade. Time to improvement is defined as the time from the initial onset date (inclusive) of the maximum grade to the first onset date that the toxicity grade is below the maximum grade with no higher grade thereafter, or the resolution date, whichever occurs first.	From randomization date through 30 days after the last dose of drug (up to 24 months)