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
6 other identifiers
interventional
122
18 countries
111
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Aug 2017
Typical duration for phase_2
111 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 22, 2017
CompletedFirst Posted
Study publicly available on registry
May 31, 2017
CompletedStudy Start
First participant enrolled
August 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2020
CompletedResults Posted
Study results publicly available
October 27, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
November 26, 2021
CompletedDecember 20, 2022
November 1, 2022
3 years
May 22, 2017
July 30, 2021
November 21, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (12)
Overall Survival (OS)
From date of randomization to death due to any cause (Up to approximately 3 years)
Percentage of Participants With Overall Response
From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)
Duration of Response (DOR)
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
From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)
Time to Progression (TTP)
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)
- +7 more secondary outcomes
Study Arms (2)
Pomalidomide 4 mg + Dexamethasone 40 mg
ACTIVE COMPARATORPomalidomide 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.
Ixazomib 4 mg + Dexamethasone 20 mg
EXPERIMENTALIxazomib 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.
Interventions
Dexamethasone tablets
Eligibility Criteria
You may qualify if:
- Must have a confirmed diagnosis of multiple myeloma (MM) requiring therapy according to International Myeloma Working Group (IMWG) criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- 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.
- 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.
- 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.
- 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).
- Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) sampling.
- Recovered (that is, less than or equal to \[\<=\] Grade 1 nonhematologic toxicity) from the reversible effects of prior anticancer therapy.
- 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).
You may not qualify if:
- 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.
- 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.
- 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.
- Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of any cause on clinical examination during the Screening period.
- 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.
- Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of study therapy, including difficulty swallowing.
- Serious infection requiring parenteral antibiotic therapy or any other serious infection within 14 days before randomization.
- Central nervous system involvement with MM (by clinical symptoms and signs).
- 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.
- 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.
- Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (111)
Highlands Oncology Group
Fayetteville, Arkansas, 72703, United States
St Joseph Heritage Healthcare
Santa Rosa, California, 95403, United States
Lynn Cancer Institute
Boca Raton, Florida, 33486, United States
University of Florida
Gainesville, Florida, 32610, United States
University of Maryland
Baltimore, Maryland, 21201, United States
Henry Ford Health System
Detroit, Michigan, 48202, United States
Michigan State University
Lansing, Michigan, 48910, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
San Juan Oncology Associates
Farmington, New Mexico, 87401, United States
University of Toledo Medical Center
Toledo, Ohio, 43614, United States
Icon Cancer Care South Brisbane
South Brisbane, Queensland, 4101, Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, 5011, Australia
Box Hill Hospital
Box Hill, Victoria, 3128, Australia
St Vincents Hospital Melbourne
Fitzroy, Victoria, 3065, Australia
Royal Adelaide Hospital
Adelaide, Australia
GasthuisZusters Antwerpen
Wilrijk, Antwerpen, 2610, Belgium
AZ St Jan Brugge Oostende AV
Bruges, 8000, Belgium
Royal Victoria Regional Health Centre
Barrie, Ontario, L4M 6M2, Canada
Lakeridge Health Center
Ottawa, Ontario, L1G 2B9, Canada
Fakultni nemocnice Hradec Kralove
Hradec Králové, Kralovehradeck Kraj, 500 05, Czechia
University Hospital Olomouc
Olomouc, Olomouck Kraj, 775 20, Czechia
Fakultni nemocnice Kralovske Vinohrady
Prague, Praha, Hlavni Mesto, 100 34, Czechia
Vseobecna fakultni nemocnice v Praze
Prague, Praha, Hlavni Mesto, 128 08, Czechia
Fakultni nemocnice Brno
Brno, 625 00, Czechia
Fakultni nemocnice Ostrava
Ostrava, Czechia
Fakultni nemocnice Plzen
Plzen Lochotin, 304 60, Czechia
Aalborg Universitetshospital
Aalborg, North Denmark, 9100, Denmark
Regionshospitalet Holstebro
Holstebro, 7500, Denmark
Centre Antoine Lacassagne Centre Regional de Lutte Contre Le Cancer
Nice, Alpes-Maritimes, 06189, France
CHRU Dijon Complexe Du Bocage
Dijon, Cote-d'Or, 21034, France
CHRU de Brest - Hopital Morvan
Brest, Finistere, 29609, France
CHRU Nancy
Vandœuvre-lès-Nancy, Meurthe-et-Moselle, 54511, France
Centre Hospitalier Bretagne Atlantique Vannes
Vannes, Morbihan, 56017, France
Centre Hospitalier Le Mans
Le Mans, Sarthe, 72037, France
Groupe Hospitalier du Havre
Montivilliers, Seine-Maritime, 76290, France
CHU Amiens Hopital Sud
Amiens, 80054, France
Centre Hospitalier Fleyriat
Bourg-en-Bresse, 01012, France
Centre Hospitalier (CH) William Morey
Chalon-sur-Saône, 71100, France
Hospital d Instructions des Armees Percy
Clamart, 92140, France
Centre Hospitalier de Dunkerque
Dunkirk, 59240, France
Centre Jean Bernard Clinique Victor Hugo
Le Mans, 72015, France
Centre Hospitalier Regional d'Orleans
Orléans, 45100, France
Centre Hospitalier de Perigueux
Périgueux, 24000, France
CHRU de Poitiers La Miletrie
Poitiers, 86021, France
CHRU Rennes
Rennes, 35033, France
Centre Henri Becquerel
Rouen, 76038, France
Uberortliche Gemeinschaftspraxis Pasing und Furstenfeldbruck
München, Bavaria, 81241, Germany
Universitatsklinikum Dusseldorf
Düsseldorf, 40225, Germany
Asklepios Klinik Altona
Hamburg, 22763, Germany
Universitatsklinikum Tubingen
Tübingen, 72076, Germany
University General Hospital of Patras
Pátrai, Achaia, 26500, Greece
University Hospital of Alexandroupolis
Alexandroupoli, 68100, Greece
Evangelismos General Hospital of Athens
Athens, 10676, Greece
Alexandra Hospital
Athens, 11528, Greece
University General Hospital of Ioannina
Ioannina, 45500, Greece
Theageneio Anticancer Oncology Hospital of Thessaloniki
Thessaloniki, 54007, Greece
Soroka University Medical Centre
Beersheba, 84001, Israel
Bnai Zion Medical Center
Haifa, 31048, Israel
Rambam Health Corporation
Haifa, 31096, Israel
Lady Davis Carmel Medical Center
Haifa, 34362, Israel
Hadassah Medical Center
Jerusalem, 91120, Israel
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
Bologna, Emilia-Romagna, 40138, Italy
Ospedale Santa Maria Delle Croci
Ravenna, Emilia-Romagna, 48100, Italy
Arcispedale Santa Maria Nuova
Reggio Emilia, Emilia-Romagna, 42123, Italy
Ospedale Infermi di Rimini
Rimini, Emilia-Romagna, 47900, Italy
Fondazione del Piemonte per lOncologia (IRCCS)
Candiolo, Piedmont, 10060, Italy
Azienda Sanitaria Ospedaliera S Luigi Gonzaga
Orbassano, Piedmont, 10043, Italy
Azienda Ospedaliera Citta della Salute e della Scienza di Torino
Turin, Piedmont, 10126, Italy
Centro Di Riferimento Oncologico Della Basilicata
Rionero in Vulture, PZ, Italy
Azienda Ospedaliera Ospedali Riuniti Marche Nord
Pesaro, The Marches, 61122, Italy
Centro Di Riferimento Oncologico
Aviano, 33081, Italy
ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
Brescia, 25123, Italy
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST
Meldola, 47014, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Milan, 20122, Italy
Azienda Ospedaliero Universitaria Di Modena Policlinico
Modena, 41100, Italy
Azienda Ospedaliero Universitaria di Parma
Parma, 43100, Italy
Ospedale Santa Maria Della Misericordia
Udine, 33100, Italy
Azienda ULSS 6 Vicenza
Vicenza, 36100, Italy
Albert Schweitzer Ziekenhuis
Dordrecht, South Holland, 3318 AT, Netherlands
Zuyderland Medisch Centrum
Sittard, 6162 BG, Netherlands
Oslo Universitetssykehus HF Rikshospitalet
Oslo, Oppland, N-1346, Norway
Haukeland Universitetssykehus
Bergen, N-5021, Norway
Forde Sentralsjukehus
Førde, 6812, Norway
Stavanger Universitetssykehus
Stavanger, N-4011, Norway
St Olavs Hospital
Trondheim, N-7006, Norway
Kirov Research Institute of Haematology and Blood Transfusion
Kirov, 610027, Russia
Moscow Clinical Scientific Center
Moscow, 111123, Russia
City Clinical Hospital n a S P Botkin
Moscow, 125284, Russia
City Clinical Hospital # 40
Moscow, 129301, Russia
Samara State Medical University
Samara, 433021, Russia
Hospital Universitario Infanta Leonor
Madrid, Madrid, Communidad Delaware, 28031, Spain
Hospital Universitari de Girona Dr Josep Trueta
Girona, 17007, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Helsingborg Lasarett
Helsingborg, Skåne County, SE-25187, Sweden
Sodra Alvsborgs Sjukhus Boras
Borås, SE-50182, Sweden
Norrlands Universitetssjukhus
Umeå, 901 85, Sweden
Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
Ankara, 06200, Turkey (Türkiye)
Gazi University Medical Faculty Gazi Hospital
Ankara, 06500, Turkey (Türkiye)
Ankara University Medical Faculty Cebeci Hospital
Ankara, 06590, Turkey (Türkiye)
Dokuz Eylul University Medical Faculty
Izmir, 35340, Turkey (Türkiye)
Ege Universitesi Tip Fakultesi Hastanesi
Izmir, Turkey (Türkiye)
Erciyes Universitesi Tip Fakultesi Hastanesi
Kayseri, 38039, Turkey (Türkiye)
Royal Cornwall Hospital
Truro, Cornwall, TR1 3LJ, United Kingdom
Betsi Cadwaladr University Health Board
Bodelwyddan, Denbighshire-SirDdinbych, LL18 5UJ, United Kingdom
Royal Bournemouth Hospital
Bournemouth, Dorset, BH7 7DW, United Kingdom
Kent and Canterbury Hospital
Canterbury, Kent, CT1 3NG, United Kingdom
GenesisCare Oxford
Oxford, Oxfordshire, OX4 6LB, United Kingdom
Royal Stoke University Hospital
Stoke-on-Trent, Staffordshire, ST4 6QG, United Kingdom
Leicester Royal Infirmary
Leicester, LE1 5WW, United Kingdom
Singleton Hospital
Swansea, SA2 8QA, United Kingdom
New Cross Hospital
Wolverhampton, WV10 0QP, United Kingdom
Related Publications (1)
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.
PMID: 35075109DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 22, 2017
First Posted
May 31, 2017
Study Start
August 1, 2017
Primary Completion
August 1, 2020
Study Completion
November 26, 2021
Last Updated
December 20, 2022
Results First Posted
October 27, 2021
Record last verified: 2022-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, 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.
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.