Clinical trial NCT03170882: A Study of Ixazomib, Given With Dexamethasone in Adults With Multiple Myeloma
Official title: A Phase 2, Randomized, Open-Label Study Comparing Oral Ixazomib/Dexamethasone and Oral Pomalidomide/Dexamethasone in Relapsed and/or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed and/or Refractory Multiple Myeloma
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-05-31
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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:
measure: Overall Survival (OS)
timeFrame: From date of randomization to death due to any cause (Up to approximately 3 years)
measure: Percentage of Participants With Overall Response
timeFrame: From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)
measure: Duration of Response (DOR)
timeFrame: 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)
measure: Time to Response
timeFrame: From date of randomization until first documentation of CR, VGPR or PR (Up to approximately 3 years)
measure: Time to Progression (TTP)
timeFrame: 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)
measure: 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
timeFrame: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
measure: HRQOL Based on EORTC QLQ-C30 SubScale Score
timeFrame: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
measure: HRQOL Based on EORTC Multiple Myeloma Module 20 (EORTC QLQ-MY20) Score
timeFrame: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
measure: Number of Participants With Responses to HRQOL Based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score
timeFrame: End of Treatment (Up to 28 cycles, each cycle was of 28 days)
measure: HRQOL Based on EuroQol Visual Analogue Scale (EQ VAS) Score
timeFrame: Baseline and End of Treatment (Up to 28 cycles, each cycle was of 28 days)
measure: Health Care Utilization (HU): Number of Participants With at Least One Medical Encounter
timeFrame: Up to approximately 3 years
measure: HU: Duration of Medical Encounters
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Santa Rosa
country: United States
facility: St Joseph Heritage Healthcare
state: California
city: Boca Raton
country: United States
facility: Lynn Cancer Institute
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: South Brisbane
country: Australia
facility: Icon Cancer Care South Brisbane
state: Queensland
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Wilrijk
country: Belgium
facility: GasthuisZusters Antwerpen
state: Antwerpen
city: Brugge
country: Belgium
facility: AZ St Jan Brugge Oostende AV
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: Ottawa
country: Canada
facility: Lakeridge Health Center
state: Ontario
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
state: Kralovehradeck Kraj
city: Olomouc
country: Czechia
facility: University Hospital Olomouc
state: Olomouck Kraj
city: Prague
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
state: Praha, Hlavni Mesto
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
state: Praha, Hlavni Mesto
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Plzen Lochotin
country: Czechia
facility: Fakultni nemocnice Plzen
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
state: Nordjylland
city: Holstebro
country: Denmark
facility: Regionshospitalet Holstebro
city: Nice
country: France
facility: Centre Antoine Lacassagne Centre Regional de Lutte Contre Le Cancer
state: Alpes-Maritimes
city: Dijon
country: France
facility: CHRU Dijon Complexe Du Bocage
state: Cote-d'Or
city: Brest
country: France
facility: CHRU de Brest - Hopital Morvan
state: Finistere
city: Vandoeuvre Les Nancy
country: France
facility: CHRU Nancy
state: Meurthe-et-Moselle
city: Vannes
country: France
facility: Centre Hospitalier Bretagne Atlantique Vannes
state: Morbihan
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
state: Sarthe
city: Montivilliers
country: France
facility: Groupe Hospitalier du Havre
state: Seine-Maritime
city: Amiens
country: France
facility: CHU Amiens Hopital Sud
city: Bourg-en- Bresse Cedex
country: France
facility: Centre Hospitalier Fleyriat
city: Chalon sur Saone
country: France
facility: Centre Hospitalier (CH) William Morey
city: Clamart
country: France
facility: Hospital d Instructions des Armees Percy
city: Dunkerque
country: France
facility: Centre Hospitalier de Dunkerque
city: Le Mans cedex 2
country: France
facility: Centre Jean Bernard Clinique Victor Hugo
city: Orleans
country: France
facility: Centre Hospitalier Regional d'Orleans
city: Perigueux
country: France
facility: Centre Hospitalier de Perigueux
city: Poitiers
country: France
facility: CHRU de Poitiers La Miletrie
city: Rennes Cedex 9
country: France
facility: CHRU Rennes
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Munchen
country: Germany
facility: Uberortliche Gemeinschaftspraxis Pasing und Furstenfeldbruck
state: Bayern
city: Dusseldorf
country: Germany
facility: Universitatsklinikum Dusseldorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Tubingen
country: Germany
facility: Universitatsklinikum Tubingen
city: Patra
country: Greece
facility: University General Hospital of Patras
state: Achaia
city: Alexandroupoli
country: Greece
facility: University Hospital of Alexandroupolis
city: Athens
country: Greece
facility: Evangelismos General Hospital of Athens
city: Athens
country: Greece
facility: Alexandra Hospital
city: Ioannina
country: Greece
facility: University General Hospital of Ioannina
city: Thessaloniki
country: Greece
facility: Theageneio Anticancer Oncology Hospital of Thessaloniki
city: Beer Sheva
country: Israel
facility: Soroka University Medical Centre
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Haifa
country: Israel
facility: Rambam Health Corporation
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
state: Emilia-Romagna
city: Ravenna
country: Italy
facility: Ospedale Santa Maria Delle Croci
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
state: Emilia-Romagna
city: Rimini
country: Italy
facility: Ospedale Infermi di Rimini
state: Emilia-Romagna
city: Pesaro
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Marche Nord
state: Marche
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per lOncologia (IRCCS)
state: Piemonte
city: Orbassano
country: Italy
facility: Azienda Sanitaria Ospedaliera S Luigi Gonzaga
state: Piemonte
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta della Salute e della Scienza di Torino
state: Piemonte
city: Rionero in Vulture
country: Italy
facility: Centro Di Riferimento Oncologico Della Basilicata
state: PZ
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria Di Modena Policlinico
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Udine
country: Italy
facility: Ospedale Santa Maria Della Misericordia
city: Vicenza
country: Italy
facility: Azienda ULSS 6 Vicenza
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
state: Zuid-Holland
city: Sittard
country: Netherlands
facility: Zuyderland Medisch Centrum
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF Rikshospitalet
state: Oppland
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus
city: Forde
country: Norway
facility: Forde Sentralsjukehus
city: Stavanger
country: Norway
facility: Stavanger Universitetssykehus
city: Trondheim
country: Norway
facility: St Olavs Hospital
city: Kirov
country: Russian Federation
facility: Kirov Research Institute of Haematology and Blood Transfusion
city: Moscow
country: Russian Federation
facility: Moscow Clinical Scientific Center
city: Moscow
country: Russian Federation
facility: City Clinical Hospital n a S P Botkin
city: Moscow
country: Russian Federation
facility: City Clinical Hospital # 40
city: Samara
country: Russian Federation
facility: Samara State Medical University
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
state: Madrid, Communidad Delaware
city: Girona
country: Spain
facility: Hospital Universitari de Girona Dr Josep Trueta
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Helsingborg
country: Sweden
facility: Helsingborg Lasarett
state: Skane Lan
city: Boras
country: Sweden
facility: Sodra Alvsborgs Sjukhus Boras
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty Gazi Hospital
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty Cebeci Hospital
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medical Faculty
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Hastanesi
city: Kayseri
country: Turkey
facility: Erciyes Universitesi Tip Fakultesi Hastanesi
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
state: Cornwall
city: Bodelwyddan
country: United Kingdom
facility: Betsi Cadwaladr University Health Board
state: Denbighshire-SirDdinbych
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: Dorset
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: Kent
city: Oxford
country: United Kingdom
facility: GenesisCare Oxford
state: Oxfordshire
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke University Hospital
state: Staffordshire
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Swansea
country: United Kingdom
facility: Singleton Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.