A Study of Ixazomib, Given With Dexamethasone in Adults With Multiple Myeloma

A Phase 2, Randomized, Open-Label Study Comparing Oral Ixazomib/Dexamethasone and Oral Pomalidomide/Dexamethasone in Relapsed and/or Refractory Multiple Myeloma

The main aim of this study is to learn if ixazomib, given with dexamethasone, stops the cancer from getting worse in people with relapsed or refractory multiple myeloma. It will be compared to another medicine called pomalidomide, given with dexamethasone with people with the same condition. Relapsed means the previous cancer treatment stopped working, over time. Refractory means they did not respond to previous cancer treatment. Another aim is to check for side effects from the study medicines.

At the first visit, the study doctor will check who can take part. Participants who can take part will be picked for 1 of 2 treatments by chance.

• Ixazomib capsules, given with dexamethasone tablets
• Pomalidomide capsules, given with dexamethasone tablets

All participants will take their study medicine on specific days during a 28-day cycle.

The 1st dose of study medicines in each 28-day cycle will take place in the clinic, The other doses of the study medicines will be taken at home. This will happen for 6 cycles. After this, all study medicines will be taken at home.

After treatment, participants will visit the clinic every 12 weeks for a check-up.

If participants cannot attend their clinic for an important reason (for example, due to the COVID-19 pandemic), the clinic will make alternative arrangements using their local procedures.

Study Overview

• Status: Completed
• Conditions: Relapsed and/or Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Ixazomib; Drug: Pomalidomide; Drug: Dexamethasone

Detailed Description

The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have relapsed and/or refractory multiple myeloma (RRMM). This study will compare the efficacy and safety in participants who take ixazomib and dexamethasone to pomalidomide and dexamethasone. It is an open-label, Phase 2 study.

The study will enroll approximately 120 participants. Participants will receive:

• Ixazomib 4 mg + dexamethasone 20 mg (or 10 mg if participant is aged >=75 years) OR
• Pomalidomide 4 mg + dexamethasone 40 mg (or 20 mg if participant is aged >=75 years)

All participants will be asked to take either ixazomib plus dexamethasone (in cases where only 4 mg tablets for dexamethasone are available, the following dexamethasone schedule is recommended for participants aged >=75 years: 12 mg dexamethasone will be given on Days 1, 8, 15, and 22 of every 28-day cycle; and 8 mg dexamethasone will be given on Days 2, 9, 16, and 23 of every 28-day cycle) or pomalidomide 4 mg + dexamethasone 40 mg at recommended doses.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 28 months after the first participant enters the study.

Participants will make multiple visits to the clinic, and will be contacted for progression free-survival (PFS) follow-up, in case of study drug discontinuation for up to 4 years from first dose administration. After disease progression, participants will be followed-up for overall survival (OS) every 12 weeks until death or up to 4 years.

Alternative methods for administering study procedures/assessments may be considered when it is not possible for the participants to come to the study site due to extenuating circumstances (e.g., due to the COVID-19 pandemic).

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Royal Adelaide Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Care South Brisbane
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Fitzroy, Victoria, Australia, 3065
      • St Vincents Hospital Melbourne
• Belgium
  • Brugge, Belgium, 8000
    • AZ ST JAn Brugge Oostende AV
  • Antwerpen
    • Wilrijk, Antwerpen, Belgium, 2610
      • GasthuisZusters Antwerpen
• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre
    • Ottawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Center
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno
  • Ostrava, Czechia
    • Fakultni nemocnice Ostrava
  • Plzen Lochotin, Czechia, 304 60
    • Fakultni nemocnice Plzen
  • Kralovehradeck Kraj
    • Hradec Kralove, Kralovehradeck Kraj, Czechia, 500 05
      • Fakultni nemocnice Hradec Kralove
  • Olomouck Kraj
    • Olomouc, Olomouck Kraj, Czechia, 775 20
      • University Hospital Olomouc
  • Praha, Hlavni Mesto
    • Prague, Praha, Hlavni Mesto, Czechia, 100 34
      • Fakultni nemocnice Kralovske Vinohrady
    • Praha, Praha, Hlavni Mesto, Czechia, 128 08
      • Vseobecna fakultni nemocnice v Praze
• Denmark
  • Holstebro, Denmark, 7500
    • Regionshospitalet Holstebro
  • Nordjylland
    • Aalborg, Nordjylland, Denmark, 9100
      • Aalborg Universitetshospital
• France
  • Amiens, France, 80054
    • CHU Amiens Hôpital sud
  • Bourg-en- Bresse Cedex, France, 01012
    • Centre Hospitalier Fleyriat
  • Chalon sur Saone, France, 71100
    • Centre Hospitalier (CH) William Morey
  • Clamart, France, 92140
    • Hospital d Instructions des Armees Percy
  • Dunkerque, France, 59240
    • Centre Hospitalier de Dunkerque
  • Le Mans cedex 2, France, 72015
    • Centre Jean Bernard Clinique Victor Hugo
  • Orleans, France, 45100
    • Centre Hospitalier Régional D'orléans
  • Perigueux, France, 24000
    • Centre Hospitalier de Perigueux
  • Poitiers, France, 86021
    • CHRU de Poitiers La Miletrie
  • Rennes Cedex 9, France, 35033
    • CHRU Rennes
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06189
      • Centre Antoine Lacassagne Centre Régional de Lutte Contre Le Cancer
  • Cote-d'Or
    • Dijon, Cote-d'Or, France, 21034
      • CHRU Dijon Complexe Du Bocage
  • Finistere
    • Brest, Finistere, France, 29609
      • CHRU de Brest - Hôpital Morvan
  • Meurthe-et-Moselle
    • Vandoeuvre Les Nancy, Meurthe-et-Moselle, France, 54511
      • CHRU Nancy
  • Morbihan
    • Vannes, Morbihan, France, 56017
      • Centre Hospitalier Bretagne Atlantique Vannes
  • Sarthe
    • Le Mans, Sarthe, France, 72037
      • Centre Hospitalier Le Mans
  • Seine-Maritime
    • Montivilliers, Seine-Maritime, France, 76290
      • Groupe Hospitalier Du Havre
• Germany
  • Dusseldorf, Germany, 40225
    • Universitatsklinikum Dusseldorf
  • Hamburg, Germany, 22763
    • Asklepios Klinik Altona
  • Tubingen, Germany, 72076
    • Universitatsklinikum Tubingen
  • Bayern
    • Munchen, Bayern, Germany, 81241
      • Uberortliche Gemeinschaftspraxis Pasing und Furstenfeldbruck
• Greece
  • Alexandroupoli, Greece, 68100
    • University Hospital of Alexandroupolis
  • Athens, Greece, 11528
    • Alexandra Hospital
  • Athens, Greece, 10676
    • Evangelismos General Hospital of Athens
  • Ioannina, Greece, 45500
    • University General Hospital of Ioannina
  • Thessaloniki, Greece, 54007
    • Theageneio Anticancer Oncology Hospital of Thessaloniki
  • Achaia
    • Patra, Achaia, Greece, 26500
      • University General Hospital of Patras
• Israel
  • Beer Sheva, Israel, 84001
    • Soroka University Medical Centre
  • Haifa, Israel, 34362
    • Lady Davis Carmel Medical Center
  • Haifa, Israel, 31048
    • Bnai Zion Medical Center
  • Haifa, Israel, 31096
    • Rambam Health Corporation
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
• Italy
  • Aviano, Italy, 33081
    • Centro di Riferimento Oncologico
  • Brescia, Italy, 25123
    • ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
  • Meldola, Italy, 47014
    • Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST
  • Milano, Italy, 20122
    • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
  • Modena, Italy, 41100
    • Azienda Ospedaliero Universitaria Di Modena Policlinico
  • Parma, Italy, 43100
    • Azienda Ospedaliero Universitaria di Parma
  • Udine, Italy, 33100
    • Ospedale Santa Maria della Misericordia
  • Vicenza, Italy, 36100
    • Azienda ULSS 6 Vicenza
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
    • Ravenna, Emilia-Romagna, Italy, 48100
      • Ospedale Santa Maria delle Croci
    • Reggio Emilia, Emilia-Romagna, Italy, 42123
      • Arcispedale Santa Maria Nuova
    • Rimini, Emilia-Romagna, Italy, 47900
      • Ospedale Infermi di Rimini
  • Marche
    • Pesaro, Marche, Italy, 61122
      • Azienda Ospedaliera Ospedali Riuniti Marche Nord
  • PZ
    • Rionero in Vulture, PZ, Italy
      • Centro di Riferimento Oncologico della Basilicata
  • Piemonte
    • Candiolo, Piemonte, Italy, 10060
      • Fondazione del Piemonte per lOncologia (IRCCS)
    • Orbassano, Piemonte, Italy, 10043
      • Azienda Sanitaria Ospedaliera S Luigi Gonzaga
    • Torino, Piemonte, Italy, 10126
      • Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino
• Netherlands
  • Sittard, Netherlands, 6162 BG
    • Zuyderland Medisch Centrum
  • Zuid-Holland
    • Dordrecht, Zuid-Holland, Netherlands, 3318 AT
      • Albert Schweitzer Ziekenhuis
• Norway
  • Bergen, Norway, N-5021
    • Haukeland Universitetssykehus
  • Forde, Norway, 6812
    • Forde Sentralsjukehus
  • Stavanger, Norway, N-4011
    • Stavanger Universitetssykehus
  • Trondheim, Norway, N-7006
    • St Olavs Hospital
  • Oppland
    • Oslo, Oppland, Norway, N-1346
      • Oslo Universitetssykehus HF Rikshospitalet
• Russian Federation
  • Kirov, Russian Federation, 610027
    • Kirov Research Institute of Haematology and Blood Transfusion
  • Moscow, Russian Federation, 129301
    • City Clinical Hospital # 40
  • Moscow, Russian Federation, 111123
    • Moscow Clinical Scientific Center
  • Moscow, Russian Federation, 125284
    • City Clinical Hospital n a S P Botkin
  • Samara, Russian Federation, 433021
    • Samara State Medical University
• Spain
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Dr Josep Trueta
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Madrid, Communidad Delaware
    • Madrid, Madrid, Communidad Delaware, Spain, 28031
      • Hospital Universitario Infanta Leonor
• Sweden
  • Boras, Sweden, SE-50182
    • Södra Älvsborgs Sjukhus Borås
  • Umea, Sweden, 901 85
    • Norrlands universitetssjukhus
  • Skane Lan
    • Helsingborg, Skane Lan, Sweden, SE-25187
      • Helsingborg Lasarett
• Turkey
  • Ankara, Turkey, 06590
    • Ankara University Medical Faculty Cebeci Hospital
  • Ankara, Turkey, 06200
    • Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
  • Ankara, Turkey, 06500
    • Gazi University Medical Faculty Gazi Hospital
  • Izmir, Turkey, 35340
    • Dokuz Eylul University Medical Faculty
  • Izmir, Turkey
    • Ege Universitesi Tip Fakultesi Hastanesi
  • Kayseri, Turkey, 38039
    • Erciyes Universitesi Tip Fakultesi Hastanesi
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • Swansea, United Kingdom, SA2 8QA
    • Singleton Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospital
  • Denbighshire-SirDdinbych
    • Bodelwyddan, Denbighshire-SirDdinbych, United Kingdom, LL18 5UJ
      • Betsi Cadwaladr University Health Board
  • Dorset
    • Bournemouth, Dorset, United Kingdom, BH7 7DW
      • Royal Bournemouth Hospital
  • Kent
    • Canterbury, Kent, United Kingdom, CT1 3NG
      • Kent and Canterbury Hospital
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX4 6LB
      • GenesisCare Oxford
  • Staffordshire
    • Stoke-on-Trent, Staffordshire, United Kingdom, ST4 6QG
      • Royal Stoke University Hospital
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Santa Rosa, California, United States, 95403
      • St Joseph Heritage Healthcare
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Lansing, Michigan, United States, 48910
      • Michigan State University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Mexico
    • Farmington, New Mexico, United States, 87401
      • San Juan Oncology Associates
  • Ohio
    • Toledo, Ohio, United States, 43614
      • University of Toledo Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Must have a confirmed diagnosis of multiple myeloma (MM) requiring therapy according to International Myeloma Working Group (IMWG) criteria.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
3. Must have had a relapse or progressive disease (PD) after having received 2 or more prior lines of systemic therapy. Note: A line of therapy is defined as 1 or more cycles of a planned treatment program; this may consist of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation (SCT), followed by maintenance is considered 1 line of therapy. Typically each line of therapy is separated by PD. Discussion with the medical monitor may help clarify the number of lines of therapy that a prospective study participant had.
4. Must be refractory to lenalidomide, defined as having received at least 2 consecutive cycles of lenalidomide as a single agent or within a lenalidomide-containing regimen and having had PD during treatment with or within 60 days after the last dose of lenalidomide. The starting dose of lenalidomide should have been 25 mg (or as low as 10 mg in the case of renal function impairment or other safety concern), and the final dose should have been a minimum of 10 mg.

5. Must have received at least 2 consecutive cycles of a bortezomib- or carfilzomib-containing regimen, and either:

   • Achieved at least a partial response (PR) and did not have PD during treatment with or within 60 days after the last dose of bortezomib or carfilzomib, OR
   • Had bortezomib and/or carfilzomib intolerance (defined as discontinuation because of drug-related adverse events [AEs] before completion of the planned treatment course) without PD before the start of the next regimen.

6. Must have measurable disease defined by:

   • Serum M-protein >=1 g/dL (>=10 g/L), OR
   • Urine M-protein >=200 mg/24 hours and must have documented MM isotype by immunofixation (central laboratory).
7. Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) sampling.
8. Recovered (that is, less than or equal to [<=] Grade 1 nonhematologic toxicity) from the reversible effects of prior anticancer therapy.
9. Must be willing and able to adhere to pomalidomide-related risk mitigation activities if randomized to the pom+dex arm (example, Risk Evaluation and Mitigation Strategies [REMS], pregnancy prevention programs).

Exclusion Criteria:

1. Prior allogenic bone marrow transplantation in any prior line of therapy or prior autologous SCT in the last prior line of therapy- unless the autologous SCT was performed a year or more before disease progression.
2. Diagnosed with or treated for another malignancy within 2 years before randomization, or previously diagnosed with another malignancy and have any evidence of residual, persistent, or recurrent disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
3. Diagnosis of smoldering MM, Waldenström's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
4. Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of any cause on clinical examination during the Screening period.
5. Treatment with any investigational products or with chimeric or fully human monoclonal antibodies within 30 days before randomization, systemic anticancer therapy or radiotherapy within 14 days before randomization (Note: "spot" radiation for areas of pain is permitted), and major surgery within 14 days before randomization.
6. Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of study therapy, including difficulty swallowing.
7. Serious infection requiring parenteral antibiotic therapy or any other serious infection within 14 days before randomization.
8. Central nervous system involvement with MM (by clinical symptoms and signs).
9. Ongoing or active systemic infection, known human immunodeficiency virus-ribonucleic acid (RNA) positive, known hepatitis B surface antigen seropositive, or known hepatitis C virus-RNA positive.
10. Systemic treatment with strong cytochrome P-450 3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort within 14 days before randomization.
11. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
12. History of severe cutaneous reactions, including hypersensitivity reactions such as Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), in the context of treatment with lenalidomide or thalidomide.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pomalidomide 4 mg + Dexamethasone 40 mg; Pomalidomide 4 mg, capsules, orally, once daily on Days 1 to 21 of each 28-day cycle, plus dexamethasone 40 mg, (or 20 mg if participant is aged >=75 years), tablets, orally, once daily on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years.	Drug: Pomalidomide; Pomalidomide capsules; Drug: Dexamethasone; Dexamethasone tablets
Experimental: Ixazomib 4 mg + Dexamethasone 20 mg; Ixazomib 4 mg as starting dose, capsules, orally, once daily on Days 1, 8, and 15 of each 28-day cycle, with escalation to 5.5 mg at the start of Cycle 2 for participants who tolerated the 4 mg dose in Cycle 1, plus dexamethasone 20 mg (or 10 mg if participant is aged >=75 years), tablets, orally, once daily on Days 1, 2, 8, 9, 15, 16, 22, and 23 of every 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study up to 2 years.	Drug: Ixazomib; Ixazomib capsules; Other Names: MLN9708; NINLARO; Drug: Dexamethasone; Dexamethasone tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS: Time from randomization to first occurrence of confirmed progressive disease (PD) as assessed by investigator by International Myeloma Working Group(IMWG) response criteria/death from any cause, whichever occurs first. PD requires following: Increase of >=25 % from nadir in: Serum M component (increase must be >=0.5 gram per deciliter [g/dl]); Urine M-component (increase must be >=200 milligram [mg]/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved free light chain (FLC) increase of >10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: bone marrow plasma cell percentage must be >=10%; Development of new/increase in size of existing bone lesions/soft tissue plasmacytomas; development of hypercalcemia (>11.5mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease.	From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to death from any cause, up to 3 years are reported.	From date of randomization to death due to any cause (Up to approximately 3 years)
Percentage of Participants With Overall Response	Overall Response Rate (ORR) was defined as the percentage of participants who achieved partial response (PR), very good partial response (VGPR), or complete response (CR) based on laboratory results and IRC assessment using modified IMWG criteria. PR: >=50% reduction of serum M protein + reduction in 24-hour urinary M protein by >=90% or to <200 mg/24-hour; if M protein is not measurable, >=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, >=50% reduction in bone marrow plasma cells, when baseline value >=30% and; if present at baseline, >=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein + urine M-protein level <100 mg/24-hour. CR: negative immunofixation on serum + urine; disappearance of soft tissue plasmacytomas; <5 % plasma cells in bone marrow.	From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)
Duration of Response (DOR)	DOR: Time from first documentation of CR/PR/VGPR to first documentation of PD. Per IMWG criteria, PR:>=50% reduction of serum M protein+reduction in 24-hour urinary M protein by >=90% to <200 mg/24-hour or >=50% decrease in difference between involved and uninvolved FLC levels/ >=50% reduction in bone marrow plasma cells, if >=30% at Baseline/ >=50% reduction in size of soft tissue plasmacytomas. VGPR: serum+urine M-protein detectable by immunofixation but not on electrophoresis/ >=90% reduction in serum M-protein + urine M-protein level <100 mg/24-hour. CR:negative immunofixation on serum + urine+disappearance of soft tissue plasmacytomas+<5% plasma cells in bone marrow. PD:serum M-component increase >=0.5 g/dl or urine M-component increase >=200 mg/24-hour/ difference between involved and uninvolved FLC levels increase >10 mg/dl or bone marrow plasma cell >=10%/development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia.	From date of first documentation of CR, VGPR or PR until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)
Time to Response	Time to response was defined as the time from randomization to the first documentation of PR/VGPR/CR. Per IMWG criteria, PR: >=50% reduction of serum M protein + reduction in 24-hour urinary M protein by >=90% or to <200 mg/24-hour; if M-protein is not measurable, >=50% decrease in difference between involved and uninvolved FLC levels is required; if not measurable by FLC, >=50% reduction in bone marrow plasma cells, when Baseline value >=30% and; if present at Baseline, >=50% reduction in size of soft tissue plasmacytomas is required. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein + urine M-protein level <100 mg/24-hour. CR: negative immunofixation on serum + urine; disappearance of soft tissue plasmacytomas; <5% plasma cells in bone marrow.	From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)
Time to Progression (TTP)	TTP was defined as the time from the date of randomization to first documentation of PD. Per IMWG criteria, PD required 1 of the following: Increase of >=25% from nadir in: Serum M-component (increase must be >=0.5 g/dl; Urine M-component (increase must be >=200 mg/24-hour); In participants without measurable serum and urine M-protein levels difference between involved and uninvolved FLC levels increase of >10 mg/dl; In participants without measurable serum and urine M protein levels and without measurable disease by FLC level: Bone marrow plasma cell percentage must be >=10%; Development of new or increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (>11.5 mg/dL corrected serum calcium) attributed solely to plasma cell proliferative disease.	From date of randomization until first occurrence of confirmed disease progression or death due to any cause, whichever occurs first (Up to approximately 3 years)
Health-Related Quality of Life (HRQOL) Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score	The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/quality of life (QOL) scale. The physical domain consisted of 5 items covering participant's daily physical activities on a scale from 1 (not at all) to 4 (very much). Raw scores were linearly transformed to a total score between 0-100, with a high score indicating better physical functioning.	Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score	The EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 symptoms scales (disease symptoms, side effects of treatment), and 2 functional subscales (body image, future perspective). Scores were averaged and transformed to 0-100 scale. Higher scores for the future perspective scale indicate better perspective of the future, for the body image scale indicate better body image and for the disease symptoms scale indicate higher level of symptomatology.	Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score	EQ-5D-5L comprises of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extremely severe problems. Higher scores indicated greater levels of problems across the five dimensions.	End of Treatment (Up to 28 cycles, each cycle was of 28 days)
HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score	The EQ VAS records the respondent's self-rated health on a 20 centimeter (cm), vertical, visual analogue scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores from all dimensions were combined into a single index score that was reported, where higher score was better quality of life.	Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter	Healthcare resources used during medical encounters included hospitalizations, emergency room stays, or outpatient visits. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice).	Up to approximately 3 years
HU: Duration of Medical Encounters	Duration of healthcare resources used during medical encounters including hospitalizations, emergency room stays, or outpatient visits was reported in days. A hospitalization was defined as at least 1 overnight stay in an Intensive Care Unit and/or non-Intensive Care Unit (acute care unit, palliative care unit, and hospice).	Up to approximately 3 years
HRQOL Based on EORTC QLQ-C30 SubScale Score	The EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a QOL scale. Most of the 30 items had 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Each subscale raw score were linearly transformed to a total score between 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL. The Physical domain of the functional subscale is reported in the secondary outcome measure 7.	Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Dimopoulos MA, Schjesvold F, Doronin V, Vinogradova O, Quach H, Leleu X, Montes YG, Ramasamy K, Pompa A, Levin MD, Lee C, Mellqvist UH, Fenk R, Demarquette H, Sati H, Vorog A, Labotka R, Du J, Darif M, Kumar S. Oral ixazomib-dexamethasone vs oral pomalidomide-dexamethasone for lenalidomide-refractory, proteasome inhibitor-exposed multiple myeloma: a randomized Phase 2 trial. Blood Cancer J. 2022 Jan 24;12(1):9. doi: 10.1038/s41408-021-00593-2.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): November 26, 2021

Study Registration Dates

• First Submitted: May 22, 2017
• First Submitted That Met QC Criteria: May 26, 2017
• First Posted (Actual): May 31, 2017

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: November 21, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Pomalidomide; Ixazomib
• Other Study ID Numbers: C16029; 2016-004742-28 (EudraCT Number); U1111-1188-2677 (Other Identifier: WHO); 2017/1235 (Registry Identifier: Norwegian Medicines Agency); N-20170083 (Registry Identifier: Danish Medicines Agency); 17/NW/0546 (Registry Identifier: NRES)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No