Clinical trial NCT05257083: A Study of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma
Official title: A Phase 3 Randomized Study Comparing Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Cellular Therapy
CAR-T Therapy
BCMA CAR-T
Newly Diagnosed Multiple Myeloma
Lead sponsor: European Myeloma Network B.V.
Sponsor class: NETWORK
Collaborators: name: Janssen Research & Development, LLC
First posted: 2022-02-25
Enrollment: 750
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 purpose of this study is to compare the efficacy of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Ciltacabtagene Autoleucel versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Autologous Stem Cell Transplant (ASCT) in newly diagnosed multiple myeloma patients.

Detailed description: Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function.

JNJ-68284528 (ciltacabtagene autoleucel \[cilta-cel\]) is an autologous chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA) that is being evaluated to treat participants with multiple myeloma. The primary hypothesis is that in transplant-eligible participants with newly diagnosed multiple myeloma (NDMM), cilta-cel will significantly improve progression-free survival (PFS) and Sustained MRD-negative CR rate compared with Autologous Stem Cell Transplant (ASCT).

Approximately 750 participants (375 per arm) will be randomly assigned in a 1:1 ratio into 2 arms.

Eligibility criteria: Inclusion Criteria:

* Participants with documented NDMM according to IMWG diagnostic criteria, for whom high-dose therapy and ASCT are part of the intended initial treatment plan.
* Measurable disease, as assessed by central laboratory, at screening as defined by any of the following:

  1. Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
  2. Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
* ECOG performance status of grade 0 or 1
* Clinical laboratory values within prespecified range.

Exclusion Criteria:

* Prior treatment with CAR-T therapy directed at any target.
* Any prior BCMA target therapy.
* Any prior therapy for MM or smoldering myeloma other than a short course of corticosteroids
* Received a strong cytochrome P450 (CYP)3A4 inducer within 5 half-lives prior to randomization
* Received or plans to receive any live, attenuated vaccine (except for COVID-19 vaccines) within 4 weeks prior to randomization.
* Known active, or prior history of central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM
* Stroke or seizure within 6 months of signing Informed Consent Form (ICF)

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: up to 10 years ( or 300 PFS events)
measure: Sustained MRD-negative CR
timeFrame: up to 24 months
Secondary outcomes:
measure: Overall Response (OR)
timeFrame: up to 17 years
measure: Complete Response (CR) or better status
timeFrame: up to 17 years
measure: Overall Minimal Residual Disease (MRD) -negative CR
timeFrame: up to 17 years
measure: Time to subsequent antimyeloma therapy
timeFrame: up to 17 years
measure: Progression Free Survival on Next-line Therapy (PFS2)
timeFrame: up to 17 years
measure: Overall Survival (OS)
timeFrame: up to 17 years
measure: Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score
timeFrame: up to 17 years
measure: Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score
timeFrame: up to 17 years
measure: Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Scor
timeFrame: up to 17 years
measure: Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score
timeFrame: up to 17 years
measure: Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
timeFrame: up to 280 days
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas
state: Arkansas
city: Duarte
country: United States
facility: City of Hope
state: California
city: San Diego
country: United States
facility: UC San Diego Health Moores Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF)
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: University Of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Hospital - Rochester
state: Minnesota
city: Bronx
country: United States
facility: Montefiore M-E Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Venter
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College Wisconsin
state: Wisconsin
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Herston
country: Australia
facility: Royal Brisbane and Womens Hospital
city: Melbourne
country: Australia
facility: Alfred Health
city: Melbourne
country: Australia
facility: Austin Hospital
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
city: Waratah
country: Australia
facility: Calvary Mater Newcastle Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Anderlecht
country: Belgium
facility: Jules Bordet Instituut
city: Antwerpen
country: Belgium
facility: UZA
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Edmonton
country: Canada
facility: Cross Cancer Institute
city: Hamilton
country: Canada
facility: McMaster University
city: Montréal
country: Canada
facility: Hopital Maisonneuve-Rosemont
city: Montréal
country: Canada
facility: Mcgill University Health Centre
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
city: Québec
country: Canada
facility: (CHU) Centre Hospitalier Universitaire de Quebec Laval
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Vancouver
country: Canada
facility: Vancouver General Hospital
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Králová
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Ostrava
country: Czechia
facility: Fakutni nemocnice Ostrava
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen
city: Prague
country: Czechia
facility: Vseobecna fakultni nemocnice v Prague
city: Lille
country: France
facility: CHRU de Lille - Hopital Claude Huriez
city: Lyon
country: France
facility: Hospices Civils De Lyon
city: Nantes
country: France
facility: CHU De Nantes - Hématologie Clinique
city: Poitiers
country: France
facility: CHU Poitiers - Pôle régional de Cancérologie
city: Saint-Louis
country: France
facility: Hopital Saint Louis - Aphp Hôpitaux Universitaires Saint-Louis
city: Toulouse
country: France
facility: CHU de Toulouse
city: Cologne
country: Germany
facility: University Hospital of Cologne
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg - Eppendorf
city: Leipzig
country: Germany
facility: University Hospital of Leipzig
city: Tübingen
country: Germany
facility: Tübingen
city: Würzburg
country: Germany
facility: University Hospital of Würzburg
city: Athens
country: Greece
facility: Attikon University General Hospital of Attica
city: Thessaloníki
country: Greece
facility: 'G. Papanikolaou' Hospital of Thessaloniki
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat Gan
country: Israel
facility: Sheba medical center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bunkyō-Ku
country: Japan
facility: Juntendo University Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital - Hematology/Oncology
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital-Department of Hematology
city: Hyōgo
country: Japan
facility: Hyogo College of Medicine
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Nagoya
country: Japan
facility: Nagoya City University Hospital - Department of Hematology & Oncology
city: Okayama
country: Japan
facility: Okayama University Hospital - Hematology/Oncology
city: Osaka
country: Japan
facility: Osaka metropolitan university hospital
city: Shibuya
country: Japan
facility: Japanese Red Cross Medical Center - Hematology
city: Shinjuku-Ku
country: Japan
facility: Keio University Hospital - Hematology
city: Tōhoku
country: Japan
facility: Tohoku University Hospital - Hematology
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Nijmegen
country: Netherlands
facility: Radboud UMC
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Oslo
country: Norway
facility: Oslo University Hospital Ullevål - Oncology
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Instituto Catalán de Oncología
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Pamplona
country: Spain
facility: CLINICA UNIV. DE NAVARRA, Pamplona
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santiago De Compostela
country: Spain
facility: Hospital de Santiago de Compostela
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario la Fe, Valencia
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Linköping
country: Sweden
facility: Landstinget i Ostergotland-Universitetssjukhuset i Linkoping
city: Lund
country: Sweden
facility: Skånes University Hospital Lund
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Basel
country: Switzerland
facility: Universitaetsspital Basel - Zentrum fur Hamato-Onkologie
city: Bern
country: Switzerland
facility: Universitaetsspital Bern, Inselspital
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)Département d'oncologie
city: Zürich
country: Switzerland
facility: Universitaetsspital Zuerich -Universitaeren Herzzentrum Zuerich
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Medical Centre
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
Study officials:
References: