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

NCT ID: NCT03170882

Last Updated: 2022-12-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-01
• Study Completion Date: 2021-11-26

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.

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).

Conditions

Relapsed and/or Refractory Multiple Myeloma

Keywords

Drug therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Pomalidomide

Intervention Type: DRUG

Pomalidomide capsules

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets

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.

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets

Interventions

Ixazomib

Ixazomib capsules

Intervention Type: DRUG

Pomalidomide

Pomalidomide capsules

Intervention Type: DRUG

Dexamethasone

Dexamethasone tablets

Intervention Type: DRUG

Other Intervention Names

NINLARO; MLN9708

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Highlands Oncology Group

Fayetteville, Arkansas, United States

St Joseph Heritage Healthcare

Santa Rosa, California, United States

Lynn Cancer Institute

Boca Raton, Florida, United States

University of Florida

Gainesville, Florida, United States

University of Maryland

Baltimore, Maryland, United States

Henry Ford Health System

Detroit, Michigan, United States

Michigan State University

Lansing, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

San Juan Oncology Associates

Farmington, New Mexico, United States

University of Toledo Medical Center

Toledo, Ohio, United States

Icon Cancer Care South Brisbane

South Brisbane, Queensland, Australia

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

St Vincents Hospital Melbourne

Fitzroy, Victoria, Australia

Royal Adelaide Hospital

Adelaide, , Australia

GasthuisZusters Antwerpen

Wilrijk, Antwerpen, Belgium

AZ St Jan Brugge Oostende AV

Bruges, , Belgium

Royal Victoria Regional Health Centre

Barrie, Ontario, Canada

Lakeridge Health Center

Ottawa, Ontario, Canada

Fakultni nemocnice Hradec Kralove

Hradec Králové, Kralovehradeck Kraj, Czechia

University Hospital Olomouc

Olomouc, Olomouck Kraj, Czechia

Fakultni nemocnice Kralovske Vinohrady

Prague, Praha, Hlavni Mesto, Czechia

Vseobecna fakultni nemocnice v Praze

Prague, Praha, Hlavni Mesto, Czechia

Fakultni nemocnice Brno

Brno, , Czechia

Fakultni nemocnice Ostrava

Ostrava, , Czechia

Fakultni nemocnice Plzen

Plzen Lochotin, , Czechia

Aalborg Universitetshospital

Aalborg, North Denmark, Denmark

Regionshospitalet Holstebro

Holstebro, , Denmark

Centre Antoine Lacassagne Centre Regional de Lutte Contre Le Cancer

Nice, Alpes-Maritimes, France

CHRU Dijon Complexe Du Bocage

Dijon, Cote-d'Or, France

CHRU de Brest - Hopital Morvan

Brest, Finistere, France

CHRU Nancy

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France

Centre Hospitalier Bretagne Atlantique Vannes

Vannes, Morbihan, France

Centre Hospitalier Le Mans

Le Mans, Sarthe, France

Groupe Hospitalier du Havre

Montivilliers, Seine-Maritime, France

CHU Amiens Hopital Sud

Amiens, , France

Centre Hospitalier Fleyriat

Bourg-en-Bresse, , France

Centre Hospitalier (CH) William Morey

Chalon-sur-Saône, , France

Hospital d Instructions des Armees Percy

Clamart, , France

Centre Hospitalier de Dunkerque

Dunkirk, , France

Centre Jean Bernard Clinique Victor Hugo

Le Mans, , France

Centre Hospitalier Regional d'Orleans

Orléans, , France

Centre Hospitalier de Perigueux

Périgueux, , France

CHRU de Poitiers La Miletrie

Poitiers, , France

CHRU Rennes

Rennes, , France

Centre Henri Becquerel

Rouen, , France

Uberortliche Gemeinschaftspraxis Pasing und Furstenfeldbruck

München, Bavaria, Germany

Universitatsklinikum Dusseldorf

Düsseldorf, , Germany

Asklepios Klinik Altona

Hamburg, , Germany

Universitatsklinikum Tubingen

Tübingen, , Germany

University General Hospital of Patras

Pátrai, Achaia, Greece

University Hospital of Alexandroupolis

Alexandroupoli, , Greece

Evangelismos General Hospital of Athens

Athens, , Greece

Alexandra Hospital

Athens, , Greece

University General Hospital of Ioannina

Ioannina, , Greece

Theageneio Anticancer Oncology Hospital of Thessaloniki

Thessaloniki, , Greece

Soroka University Medical Centre

Beersheba, , Israel

Bnai Zion Medical Center

Haifa, , Israel

Rambam Health Corporation

Haifa, , Israel

Lady Davis Carmel Medical Center

Haifa, , Israel

Hadassah Medical Center

Jerusalem, , Israel

Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi

Bologna, Emilia-Romagna, Italy

Ospedale Santa Maria Delle Croci

Ravenna, Emilia-Romagna, Italy

Arcispedale Santa Maria Nuova

Reggio Emilia, Emilia-Romagna, Italy

Ospedale Infermi di Rimini

Rimini, Emilia-Romagna, Italy

Fondazione del Piemonte per lOncologia (IRCCS)

Candiolo, Piedmont, Italy

Azienda Sanitaria Ospedaliera S Luigi Gonzaga

Orbassano, Piedmont, Italy

Azienda Ospedaliera Citta della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Centro Di Riferimento Oncologico Della Basilicata

Rionero in Vulture, PZ, Italy

Azienda Ospedaliera Ospedali Riuniti Marche Nord

Pesaro, The Marches, Italy

Centro Di Riferimento Oncologico

Aviano, , Italy

ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia

Brescia, , Italy

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST

Meldola, , Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, , Italy

Azienda Ospedaliero Universitaria Di Modena Policlinico

Modena, , Italy

Azienda Ospedaliero Universitaria di Parma

Parma, , Italy

Ospedale Santa Maria Della Misericordia

Udine, , Italy

Azienda ULSS 6 Vicenza

Vicenza, , Italy

Albert Schweitzer Ziekenhuis

Dordrecht, South Holland, Netherlands

Zuyderland Medisch Centrum

Sittard, , Netherlands

Oslo Universitetssykehus HF Rikshospitalet

Oslo, Oppland, Norway

Haukeland Universitetssykehus

Bergen, , Norway

Forde Sentralsjukehus

Førde, , Norway

Stavanger Universitetssykehus

Stavanger, , Norway

St Olavs Hospital

Trondheim, , Norway

Kirov Research Institute of Haematology and Blood Transfusion

Kirov, , Russia

Moscow Clinical Scientific Center

Moscow, , Russia

City Clinical Hospital n a S P Botkin

Moscow, , Russia

City Clinical Hospital # 40

Moscow, , Russia

Samara State Medical University

Samara, , Russia

Hospital Universitario Infanta Leonor

Madrid, Madrid, Communidad Delaware, Spain

Hospital Universitari de Girona Dr Josep Trueta

Girona, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Helsingborg Lasarett

Helsingborg, Skåne County, Sweden

Sodra Alvsborgs Sjukhus Boras

Borås, , Sweden

Norrlands Universitetssjukhus

Umeå, , Sweden

Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi

Ankara, , Turkey (Türkiye)

Gazi University Medical Faculty Gazi Hospital

Ankara, , Turkey (Türkiye)

Ankara University Medical Faculty Cebeci Hospital

Ankara, , Turkey (Türkiye)

Dokuz Eylul University Medical Faculty

Izmir, , Turkey (Türkiye)

Ege Universitesi Tip Fakultesi Hastanesi

Izmir, , Turkey (Türkiye)

Erciyes Universitesi Tip Fakultesi Hastanesi

Kayseri, , Turkey (Türkiye)

Royal Cornwall Hospital

Truro, Cornwall, United Kingdom

Betsi Cadwaladr University Health Board

Bodelwyddan, Denbighshire-SirDdinbych, United Kingdom

Royal Bournemouth Hospital

Bournemouth, Dorset, United Kingdom

Kent and Canterbury Hospital

Canterbury, Kent, United Kingdom

GenesisCare Oxford

Oxford, Oxfordshire, United Kingdom

Royal Stoke University Hospital

Stoke-on-Trent, Staffordshire, United Kingdom

Leicester Royal Infirmary

Leicester, , United Kingdom

Singleton Hospital

Swansea, , United Kingdom

New Cross Hospital

Wolverhampton, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Czechia; Denmark; France; Germany; Greece; Israel; Italy; Netherlands; Norway; Russia; Spain; Sweden; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 35075109 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.takeda.com/study-detail/5f6b60204db2bf003ab49572

Related Info

Other Identifiers

2016-004742-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1188-2677

Identifier Type: OTHER

Identifier Source: secondary_id

2017/1235

Identifier Type: REGISTRY

Identifier Source: secondary_id

N-20170083

Identifier Type: REGISTRY

Identifier Source: secondary_id

17/NW/0546

Identifier Type: REGISTRY

Identifier Source: secondary_id

C16029

Identifier Type: -

Identifier Source: org_study_id