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

• ClinicalTrials.gov Identifier: NCT02181413
• Recruitment Status: Active, not recruiting
• First Posted: July 4, 2014
• Results First Posted: May 7, 2019
• Last Update Posted: June 30, 2022
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma; Autologous Stem Cell Transplant	Drug: Ixazomib Citrate; Drug: Placebo	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 656 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 Citrate (MLN9708) Maintenance Therapy in Patients With Multiple Myeloma Following Autologous Stem Cell Transplant
• Actual Study Start Date: July 1, 2014
• Actual Primary Completion Date: April 16, 2018
• Estimated Study Completion Date: June 25, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ixazomib Citrate; Ixazomib citrate 3 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 4. Ixazomib citrate 4 mg, capsules, orally, once, on Days 1, 8 and 15 in a 28-day cycle for Cycles 5 through 26 until progressive disease (PD), unacceptable toxicity, or discontinuation for alternate reasons. Participants who have had any dose reductions due to adverse events (AEs) would not be dose escalated.	Drug: Ixazomib Citrate; Ixazomib citrate capsules; Other Name: MLN9708
Placebo Comparator: Placebo; Ixazomib citrate placebo-matching capsules, orally, once on Days 1, 8 and 15 in a 28-day cycle for Cycles 1 through 26 until PD, unacceptable toxicity, or discontinuation for alternate reasons.	Drug: Placebo; Ixazomib citrate placebo-matching capsules

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: 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) ]
   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.

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: Baseline up to Follow up period (107 months) ]
   OS was measured as the time from the date of randomization to the date of death.
2. Percentage of Participants With Any Best Response Category Before PD or Subsequent Therapy [ Time Frame: Baseline up to EOT (24 months) and thereafter every 4 weeks until initiation of the next line of therapy (up to 107 months) ]
   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.
3. Time to Progression (TTP) [ Time Frame: Baseline until PD (Month 107) ]
   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.
4. Second Progression Free Survival (PFS2) [ Time Frame: 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) ]
   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.
5. Time to Start of the Next Line of Therapy [ Time Frame: 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) ]
   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.
6. Time to End of the Next Line of Therapy [ Time Frame: Baseline up to end of next line of therapy (Month 107) ]
   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.
7. Duration of the Next Line of Therapy [ Time Frame: From the start of next line therapy after PD to the last dose of next line therapy (up to Month 107) ]
   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.
8. Percentage of Participants Who Develop A New Primary Malignancy [ Time Frame: Baseline until death or termination of the study (up to Month 107) ]
9. Number of Participants With Conversion From Minimal Residual Disease (MRD) Positive to MRD Negative, and Maintenance of MRD Negativity [ Time Frame: Baseline up to EOT (24 months) ]
   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.
10. Correlation Between MRD Status and Progression Free Survival (PFS) and Overall Survival (OS) [ Time Frame: Baseline up to Month 107 ]
    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.
11. OS Benefits in a High-Risk Population [ Time Frame: Randomization up to Month 107 ]
    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.
12. PFS Benefits in a High-Risk Population [ Time Frame: Randomization up to Month 107 ]
    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.
13. Eastern Cooperative Oncology Group (ECOG) Performance Score [ Time Frame: Baseline up to EOT (24 months), thereafter every 4 weeks until initiation of next line therapy ]
    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.
14. Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) or Serious Adverse Events (SAEs) [ Time Frame: First dose of study drug through 30 days after last dose of study drug (up to 24 months) ]
15. Number of Participants With Markedly Abnormal Clinical Laboratory Values [ Time Frame: Baseline through 30 days after the last dose of study drug (up to 24 months) ]
16. 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 [ Time Frame: Baseline up to PD (up to Month 107) ]
    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).
17. Plasma Concentration of Ixazomib [ Time Frame: 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 ]
    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.
18. Time to Resolution of Peripheral Neuropathy (PN) Events [ Time Frame: From randomization date through 30 days after the last dose of drug (up to 24 months) ]
    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.
19. Time to Improvement of PN Events [ Time Frame: From randomization date through 30 days after the last dose of drug (up to 24 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. 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.

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 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.

Contacts and Locations

Locations

United States, Arkansas

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

United States, Minnesota

Mayo Clinic - PPDS

Rochester, Minnesota, United States, 55905

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

United States, Pennsylvania

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States, 17033

United States, Texas

Baylor University Medical Center

Dallas, Texas, United States, 75246

United States, West Virginia

West Virginia University Hospital

Morgantown, West Virginia, United States, 26506

Argentina

Hospital Italiano de La Plata

La Plata, Buenos Aires, Argentina, B1900AX

Instituto de Hematologia Y Medicina Clinica Dr Ruben Davoli

Rosario, Santa Fe, Argentina, 2000

Sanatorio Britanico de Rosario

Rosario, Santa Fe, Argentina, S2000CVB

Sanatorio Parque de Rosario

Rosario, Santa Fe, Argentina, S2000DSV

Hospital Italiano de Buenos Aires

Ciudad Autonoma de Buenos Aires, Argentina, C1181ACH

Hospital Iturraspe

Santa Fe, Argentina, S3006FTP

Australia, New South Wales

St George Hospital

Kogarah, New South Wales, Australia, 2217

Calvary Mater Newcastle

Waratah, New South Wales, Australia, 2298

Westmead Hospital

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Icon Cancer Care South Brisbane

South Brisbane, Queensland, Australia, 4101

Gold Coast University Hospital

Southport, Queensland, Australia, 4215

Australia, South Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia, 5011

Australia, Victoria

Austin Health

Heidelberg, Victoria, Australia, 3084

The Alfred Hospital

Melbourne, Victoria, Australia, 3004

Austria

Elisabethinen Hospital Linz

Linz, Austria, 4020

Salzburger Landeskliniken

Salzburg, Austria, 5020

Allgemeines Krankenhaus der Stadt Wien

Wien, Austria, 1090

Klinik Ottakring (fruher: Wilhelminenspital)

Wien, Austria, 1160

Belgium

Centre Hospitalier Jolimont-Lobbes

La Louviere, Hainaut, Belgium, 7100

Centre Hospitalier Universitaire Ambroise Pare

Mons, Hainaut, Belgium, 7000

UZ Gent

Gent, Oost-Vlaanderen, Belgium, 9000

AZ Sint-Jan AV

Brugge, West-Vlaanderen, Belgium, 8000

ZNA Middelheim

Antwerpen, Belgium, 2020

ZNA Stuivenberg

Antwerpen, Belgium, 2060

Brazil

Hospital Das Clinicas Da Universidade Federal de Minas Gerais

Belo Horizonte, Minas Gerais, Brazil, 30130-100

Instituto de Oncologia Do Parana

Curitiba, Parana, Brazil, 80530-010

Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner

Curitiba, Parana, Brazil, 81520-060

Hospital de Clinicas de Passo Fundo

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

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

Centro de Pesquisas Oncologicas

Florianopolis, Santa Catarina, Brazil, 88034000

Instituto Joinvilense de Hematologia E Oncologia

Joinville, Santa Catarina, Brazil, 89201-260

Hospital Amaral Carvalho

Jau, Sao Paulo, Brazil, 17210-080

Hospital de Base Da FAMERP

Sao Jose Do Rio Preto, Sao Paulo, Brazil, 15090-000

Instituto Nacional de Cancer

Rio De Janeiro, Brazil, 20231-050

Universidade Federal do Rio de Janeiro - UFRJ

Rio de Janeiro, Brazil, 21941-913

Irmandade Da Santa Casa de Misericordia de Sao Paulo

Sao Paulo, Brazil, 01223-001

Hospital Israelita Albert Einstein

Sao Paulo, Brazil, 05651-901

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

Sao Paulo, Brazil, 5403000

Canada, Ontario

University Health Network

Toronto, Ontario, Canada, M5G 2N2

Canada, Quebec

MUHC-Glen Site

Montreal, Quebec, Canada, H4A 3J1

Colombia

Instituto Nacional de Cancerologia Colombia

Bogota, Cundinamarca, Colombia

Fundacion Valle Del Lili

Cali, Valle Del Cauca, Colombia

Hospital Pablo Tobon Uribe

Medellin, Colombia

Czechia

Fakultni nemocnice Hradec Kralove

Hradec Kralove, Kralovehradeck Kraj, Czechia, 500 05

Fakultni nemocnice Brno

Brno, Czechia, 625 00

Fakultni nemocnice Olomouc

Olomouc, Czechia, 779 00

Fakultni nemocnice Ostrava

Ostrava, Czechia, 708 52

Vseobecna Fakultni Nemocnice V Praze

Praha 2, Czechia, 128 08

Fakultni nemocnice Kralovske Vinohrady

Praha, Czechia, 100 34

Denmark

Herlev Hospital

Herlev, Capital, Denmark, 2730

Aalborg Universitetshospital

Aalborg, Nordjylland, Denmark, DK-9000

Aarhus Universitetshospital Arhus Sygehus

Aarhus N, Denmark, DK-8200

Rigshospitalet

Copenhagen, Denmark, 2100

Odense Universitetshospital

Odense, Denmark, 5000

Sjallands Universitetshospital, Roskilde

Roskilde, Denmark, DK-4000

Vejle Sygehus

Vejle, Denmark, DK-7100

France

Hopital Antoine Beclere

Clamart, Hauts-de-Seine, France, 92140

Hotel Dieu - Nantes

Nantes, Loire-Atlantique, France, 44093

CHRU Lille

Lille, Nord, France, 59037

Hopital Universitaire Dupuytren

Limoges, France, 87042

Groupe Hospitalier Necker Enfants Malades

Paris, France, 75015

Germany

University Clinic Heidelberg

Heidelberg, Baden-Wurttemberg, Germany, 69120

Klinikum Mannheim Universitatsklinikum gGmbH

Mannheim, Baden-Wurttemberg, Germany, 68167

Universitatsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany, 89081

LMU Klinikum der Universitat Munchen

Munchen, Bayern, Germany, 81377

Universitatsklinikum Wurzburg

Wurzburg, Bayern, Germany, 97080

Klinikum Darmstadt GmbH

Darmstadt, Hessen, Germany, 64283

Klinikum Frankfurt Hochst GmbH

Frankfurt am Main, Hessen, Germany, 65929

Pius Hospital Oldenburg

Oldenburg, Niedersachsen, Germany, 26121

Universitatsklinikum Bonn

Bonn, Nordrhein-Westfalen, Germany, 53105

Universitatsklinikum Essen

Essen, Nordrhein-Westfalen, Germany, 45122

Evangelisches Krankenhaus Essen Werden gGmbH

Essen, Nordrhein-Westfalen, Germany, 45239

Katholisches Krankenhaus Hagen gGmbH

Hagen, Nordrhein-Westfalen, Germany, 58095

Uniklinik Koln

Koln, Nordrhein-Westfalen, Germany, 50937

Universitatsmedizin der Johannes Gutenberg-Universitat Mainz

Mainz, Rheinland-Pfalz, Germany, 55131

Universitatsklinikum Carl Gustav Carus an der TU Dresden

Dresden, Sachsen, Germany, 1307

Helios Klinikum Berlin-Buch

Berlin, Germany, 13125

Charite - Universitatsmedizin Berlin

Berlin, Germany, 13353

Asklepios Klinik St. Georg

Hamburg, Germany, 20099

Universitatsklinikum Hamburg Eppendorf

Hamburg, Germany, 20246

Asklepios Klinik Altona

Hamburg, Germany, 22763

KRH Klinikum Siloah-Oststadt-Heidehaus

Hannover, Germany, 30459

Klinikum der Stadt Ludwigshafen gGmbH

Ludwigshafen, Germany, 67063

Universitatsklinikum Tubingen

Tubingen, Germany, 72076

Greece

Evangelismos General Hospital of Athens

Athens, Attiki, Greece, 10676

Laiko General Hospital of Athens

Athens, Attiki, Greece, 11527

Alexandra Hospital

Athens, Greece, 11528

Georgios Papanikolaou General Hospital of Thessaloniki

Thessaloniki, Greece, 57010

Hungary

Semmelweis Egyetem

Budapest, Hungary, 1083

Del-pesti Centrumkorhaz- Orszagos Hematologiai es Infektologiai Intezet

Budapest, Hungary, 1097

Debreceni Egyetem Klinikai Kozpont

Debrecen, Hungary, 4032

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvar, Hungary, 7400

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont

Szeged, Hungary, 6725

Israel

Barzilai Medical Center

Ashkelon, Israel, 78278

Soroka University Medical Centre

Be'er Sheva, Israel, 84101

Bnai Zion Medical Center

Haifa, Israel, 31048

Rambam Medical Center - PPDS

Haifa, Israel, 31096

Lady Davis Carmel Medical Center

Haifa, Israel, 34362

Shaare Zedek Medical Center

Jerusalem, Israel, 91031

Hadassah Medical Center PPDS -

Jerusalem, Israel, 91120

Galilee Medical Center

Nahariya, Israel, 22100

Rabin Medical Center - PPDS

Petach Tikva, Israel, 49100

Sheba Medical Center - PPDS

Ramat-Gan, Israel, 52621

Kaplan Medical Center

Rehovot, Israel, 76100

ZIV Medical Center

Safed, Israel, 13100

Tel Aviv Sourasky Medical Center PPDS

Tel Aviv, Israel, 64239

Shamir Medical Center Assaf Harofeh

Tzrifin, Israel, 70300

Italy

Presidio Ospedaliero di Pescara

Pescara, Abruzzo, Italy, 65100

Azienda Ospedaliera San Camillo Forlanini

Roma, Lazio, Italy, 152

Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, Lombardia, Italy, 27100

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

Ancona, Marche, Italy, 60020

Azienda Ospedaliera Citta della Salute e della Scienza di Torino

Torino, Piemonte, Italy, 10126

IRCCS Centro Di Riferimento Oncologico Della Basilicata

Rionero In Vulture, Potenza, Italy, 85028

Azienda Ospedaliera S Maria Di Terni

Terni, Umbria, Italy, 5100

Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi

Bologna, Italy, 40138

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

Brescia, Italy, 25123

Azienda Ospedaliera Universitaria Careggi

Firenze, Italy, 50134

IRCCS Az. Osp. Universitaria San Martino- IST

Genova, Italy, 16132

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l - PPDS

Meldola, Italy, 47014

ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda

Milano, Italy, 20162

Ospedale Infermi di Rimini

Rimini, Italy, 47900

Japan

Kobe City Medical Center General Hospital

Kobe-City, Hyogo, Japan, 650-0047

Iwate Medical University Hospital

Morioka-shi, Iwate, Japan, 020-8505

National Hospital Organization Sendai Medical Center

Sendai, Miyagi, Japan, 9838520

Niigata Cancer Center Hospital

Niigata-shi, Niigata, Japan, 951-8566

National Hospital Organization Okayama Medical Center

Okayama-City, Okayama, Japan, 701-1192

Saitama Medical Center

Kawagoe-city, Saitama, Japan, 350-8550

Juntendo University Hospital

Bunkyo, Tokyo, Japan, 113-8431

Chiba University Hospital

Chiba, Tokyo, Japan, 2608677

Japanese Red Cross Medical Center

Shibuya-ku, Tokyo, Japan, 150-8935

Keio University Hospital

Shinjuku-ku, Tokyo, Japan, 160-8582

Center Hospital of the National Center for Global Health and Medicine

Shinjuku, Tokyo, Japan, 162-8655

Kyushu University Hospital

Fukuoka-City, Japan, 812-8582

Nagoya City University Hospital

Nagoya-City, Japan, 467-8602

National Hospital Organization Nagoya Medical Center

Nagoya, Japan, 460-0001

National Hospital Organaization Shibukawa Medical Center

Shibukawa, Japan, 377-0280

National Hospital Organization Disaster Medical Center

Tachikawa, Japan, 1900014

Toyohashi Municipal Hospital

Toyohashi-City, Japan, 441-8570

Korea, Republic of

National Cancer Center

Goyang, Gyeonggido, Korea, Republic of, 410769

Chungnam National University Hospital

Daejeon, Korea, Republic of, 301-721

Gachon University Gil Medical Center Pharmacy

Incheon, Korea, Republic of, 405-760

Seoul National University Hospital

Seoul, Korea, Republic of, 110744

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

Asan Medical Center - PPDS

Seoul, Korea, Republic of, 138-736

Ewha Womans University Mokdong Hospital

Seoul, Korea, Republic of, 158710

Mexico

Centro de Investigacion Farmaceutica Especializada de Occidente, SC - PPDS

Guadalajara, Jalisco, Mexico, 44160

Hospital Universitario Dr. Jose Eleuterio Gonzalez

Monterrey, Nuevo Leon, Mexico, 64460

Netherlands

VU Medisch Centrum

Amsterdam, Noord-Holland, Netherlands, 1081 HV

Albert Schweitzer Ziekenhuis

Dordrecht, Zuid-Holland, Netherlands, 3318 AT

Universitair Medisch Centrum Groningen

Groningen, Netherlands, 9713 GZ

Erasmus MC

Rotterdam, Netherlands, 3015 CE

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands, 3584 CX

Norway

Vestre Viken HF Sykehuset Asker Og Barum

Gjelta, Oppland, Norway, N-1346

St. Olav's University Hospital

Trondheim, Sor-Trondelag, Norway, N-7030

Oslo Universitetssykehus HF, Ulleval

Oslo, Norway, 450

Stavanger Universitetssykehus

Stavanger, Norway, 4011

Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wroclawiu

Wroclaw, Dolnoslaskie, Poland, 50-367

Wojskowy Instytut Medyczny

Warszawa, Mazowieckie, Poland, 04-141

Uniwersyteckie Centrum Kliniczne

Gdansk, Pomorskie, Poland, 80-952

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich

Chorzow, Slaskie, Poland, 41-500

Szpital Specjalistyczny w Brzozowie

Brzozow, Poland, 36-200

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi

Lodz, Poland, 93-510

Portugal

Hospital de Braga

Braga, Portugal, 4710-243

Centro Hospitalar E Universitario de Coimbra EPE

Coimbra, Portugal, 3000-075

Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS

Porto, Portugal, 4200-072

Centro Hospitalar de Sao Joao, E.P.E.

Porto, Portugal, 4200-319

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

Mary Potter Oncology Centre

Pretoria, Gauteng, South Africa, 181

Albert Alberts Stem Cell Transplant Centre

Pretoria, Gauteng, South Africa, 44

Spain

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, Spain, 8916

Hospital General Universitario Gregorio Maranon

Madrid, Madrid, Communidad Delaware, Spain, 28009

Clinica Universidad Navarra

Pamplona, Navarra, Spain, 31008

Hospital Clinic de Barcelona

Barcelona, Spain, 8036

C.H. Regional Reina Sofia - PPDS

Cordoba, Spain, 14004

Institut Catala d'Oncologia Girona

Girona, Spain, 17007

Hospital Universitario de La Princesa

Madrid, Spain, 28006

Hospital Universitario La Paz - PPDS

Madrid, Spain, 28046

Hospital Universitario HM Sanchinarro CIOCC

Madrid, Spain, 28050

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, Spain, 28222

Hospital General Universitario Morales Meseguer

Murcia, Spain, 30008

Complejo Asistencial Universitario de Salamanca H. Clinico

Salamanca, Spain, 37007

Hospital Universitario Virgen del Rocio - PPDS

Sevilla, Spain, 41013

Sweden

Helsingborg Lasarett

Helsingborg, Skane Lan, Sweden

Skanes Universitetssjukhus Lund

Lund, Skane Lan, Sweden

Sahlgrenska Universitetssjukhuset

Goteborg, Vastra Gotalands Lan, Sweden

Karolinska Universitetssjukhuset Huddinge

Stockholm, Sweden, 14186

Akademiska Sjukhuset I Uppsala

Uppsala, Sweden, SE-751 85

Switzerland

Universitatsspital Basel

Basel, Basel-Stadt (de), Switzerland, 4031

Universitatsspital Zurich

Zurich, Zurich (de), Switzerland, 8091

Taiwan

Kaohsiung Medical University Hospital

Kaohsiung, Taiwan, 807

Chang Gung Medical Foundation-Kaoshiung Branch

Kaohsiung, Taiwan

National Taiwan University Hospital

Taipei, Taiwan, 10002

Chang Gung Medical Foundation Chiayi Chang Gung Memorial Hospital

Taipei, Taiwan, 613

Chang Gung Memorial Hospital, Linkou

Taoyuan City, Taiwan, 333

Thailand

Chulalongkorn University

Bangkok, Krung Thep Maha Nakhon-Bangkok, Thailand, 10330

Phramongkutklao Hospital

Bangkok, Krung Thep Maha Nakhon-Bangkok, Thailand, 10400

Turkey

Hacettepe Universitesi Tip Fakultesi Hastanesi

Ankara, Turkey, 6100

Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi

Ankara, Turkey, 6200

Ankara University Medical Faculty PPDS

Ankara, Turkey

Pamukkale Universitesi Tip Fakultesi Hastanesi

Denizli, Turkey, 20070

Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi

Istanbul, Turkey, 34093

Erciyes Universitesi Tip Fakultesi Hastanesi

Kayseri, Turkey, 38039

Karadeniz Technical University Faculty of Medicine

Trabzon, Turkey, 61080

Ukraine

MNPE Kyiv Center of Bone Marrow Transplantation of executive body of Kyiv council

Kyiv, Ukraine, 3115

United Kingdom

Southampton General Hospital

Southampton, Hampshire, United Kingdom, SO16 6YD

Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre

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

Kings College Hospital

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

Imperial College Healthcare NHS Trust

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

Churchill Hospital

Oxford, Oxfordshire, United Kingdom, OX3 7LJ

Royal Marsden Hospital - Surrey

Sutton, Surrey, United Kingdom, SM2 5PT

St James University Hospital

Leeds, Yorkshire, United Kingdom, LS9 7TF

Royal Hallamshire Hospital

Sheffield, Yorkshire, United Kingdom, S10 2JF

University Hospitals Leicester

Leicester, United Kingdom, LE1 5WW

University College London Hospitals (UCLH)

London, United Kingdom, WC1E 6AG

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] February 28, 2019

Statistical Analysis Plan  [PDF] May 31, 2018

More Information

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

Kaiser M, Beksac M, Gulbrandsen N, Schjesvold F, Hajek R, Moreau P, de Arriba de la Fuente F, Mateos MV, West S, Spencer A, Rajkumar SV, Suryanarayan K, Czorniak M, Li C, Teng Z, Labotka R, Dimopoulos MA. Adverse event management in the TOURMALINE-MM3 study of post-transplant ixazomib maintenance in multiple myeloma. Ann Hematol. 2020 Aug;99(8):1793-1804. doi: 10.1007/s00277-020-04149-5. Epub 2020 Jul 1. Erratum In: Ann Hematol. 2021 Jan;100(1):297-302.

Schjesvold F, Goldschmidt H, Maisnar V, Spicka I, Abildgaard N, Rowlings P, Cain L, Romanus D, Suryanarayan K, Rajkumar V, Odom D, Gnanasakthy A, Dimopoulos M. Quality of life is maintained with ixazomib maintenance in post-transplant newly diagnosed multiple myeloma: The TOURMALINE-MM3 trial. Eur J Haematol. 2020 May;104(5):443-458. doi: 10.1111/ejh.13379. Epub 2020 Feb 22.

Dimopoulos MA, Gay F, Schjesvold F, Beksac M, Hajek R, Weisel KC, Goldschmidt H, Maisnar V, Moreau P, Min CK, Pluta A, Chng WJ, Kaiser M, Zweegman S, Mateos MV, Spencer A, Iida S, Morgan G, Suryanarayan K, Teng Z, Skacel T, Palumbo A, Dash AB, Gupta N, Labotka R, Rajkumar SV; TOURMALINE-MM3 study group. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet. 2019 Jan 19;393(10168):253-264. doi: 10.1016/S0140-6736(18)33003-4. Epub 2018 Dec 10.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02181413
• Other Study ID Numbers: C16019; U1111-1155-8695 ( Other Identifier: WHO ); 2013-002076-41 ( EudraCT Number ); C16019CTIL ( Registry Identifier: Israel MOH ); NL.47795.029.14 ( Registry Identifier: CCMO ); 173116 ( Registry Identifier: HC-CTD ); 1036024001 ( Registry Identifier: TCTIN ); SNCTP000001745 ( Registry Identifier: SNCTP )
• First Posted: July 4, 2014
• Results First Posted: May 7, 2019
• Last Update Posted: June 30, 2022
• Last Verified: June 2022

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; Ixazomib citrate

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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protease Inhibitors; Enzyme Inhibitors