Clinical trial NCT04923893: A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Cilta-cel, a CAR-T Therapy Directed Against BCMA Versus VRd Followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants With Newly Diagnosed Multiple Myeloma for Whom ASCT is Not Planned as Initial Therapy
Official title: A Phase 3 Randomized Study Comparing Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Ciltacabtagene Autoleucel, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA Versus Bortezomib, Lenalidomide, and Dexamethasone (VRd) Followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants With Newly Diagnosed Multiple Myeloma for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Newly Diagnosed Multiple Myeloma
Cellular Therapy
CAR-T Therapy
BCMA CAR-T
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-06-11
Enrollment: 743
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 Bortezomib, Lenalidomide and Dexamethasone (VRd) induction followed by a single administration of ciltacabtagene autoleucel (cilta-cel) versus VRd induction followed by Lenalidomide and Dexamethasone (Rd) maintenance in newly diagnosed multiple myeloma participants for whom ASCT is not planned as initial therapy in terms of Progression Free Survival (PFS).

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), a molecule expressed on the surface of mature B lymphocytes and malignant plasma cells. The primary hypothesis of this study is that in participants with newly diagnosed MM, treatment with VRd induction followed by a single administration of cilta-cel will significantly improve progression free survival compared to Bortezomib, Lenalidomide and Dexamethasone (VRd) induction followed by Rd maintenance. The study will screen participants with newly diagnosed MM who are not planned to receive autologous stem cell transplant (ASCT) as initial therapy. This study will be conducted in 4 phases: Screening (up to 28 days), Pre-randomization Treatment, Treatment, and Follow-up. Assessments like patient-reported outcome(s) (PROs), electrocardiogram (ECG), vital signs and pharmacokinetics will be performed during the study. Safety evaluations will include review of adverse events, laboratory test results, vital sign measurements, physical examination findings, assessment of cardiac function, Immune-Effector Cell-Associated Encephalopathy (ICE) and handwriting assessments (only for Arm B) and Eastern Cooperative Oncology Group (ECOG) performance status. Safety data will be periodically reviewed by an Independent Data Monitoring Committee (IDMC). The duration of the study is approximately 12 years 5 months.

Eligibility criteria: Inclusion Criteria:

* Documented diagnosis of multiple myeloma (MM) according to International Myeloma Working Group (IMWG) diagnostic criteria
* Measurable disease at screening as defined by any of the following: Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=)1.0 gram per deciliter (g/dL) or urine M-protein level \>=200 milligram (mg)/24 hours; or Light chain MM in whom only measurable disease is by serum free light chain (FLC) levels: Serum immunoglobin (Ig) free light chain \>=10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa/lambda FLC ratio
* Eastern Cooperative Oncology Group Performance Status grade of 0 or 1
* Not considered for high-dose chemotherapy with Autologous Stem Cell Transplant (ASCT) due to: Ineligible due to advanced age; or Ineligible due to presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT; or Deferral of high-dose chemotherapy with ASCT as initial treatment
* A woman of childbearing potential (WOCBP) must have 2 negative highly sensitive serum or urine pregnancy tests (beta-human chorionic gonadotropin) prior to starting Bortezomib, Lenalidomide and Dexamethasone (VRd) and must agree to further testing during the study.
* Clinical laboratory values meeting the following criteria during the screening phase: hemoglobin greater than or equal to (\>=) 8.0 g/dL (\>=5 millimoles per liter \[mmol/L\]), recombinant human erythropoietin use is permitted; platelets \>=75 \*10\^9/L; absolute lymphocyte count \>=0.3 \*10\^9/L; absolute neutrophil count (ANC) \>=1.0 ×10\^9/L (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to (\<=) 3.0 \* upper limit of normal (ULN); estimated glomerular filtration rate \>=40 milliliter per minute/1.73 meter square (mL/min/1.73 m\^2) based upon modified diet in renal disease formula (MDRD-4) calculation or a 24-hour urine collection; total bilirubin \<=2.0 \* ULN; except in participants with congenital hyperbilirubinemia, such as Gilbert syndrome (in which case direct bilirubin \<=2.0 \* ULN is required)

Exclusion Criteria:

* Frailty index of \>=2 according to Myeloma Geriatric Assessment score
* Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5
* 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)
* Seropositive for human immunodeficiency virus (HIV)
* Vaccinated with live, attenuated vaccine within 4 weeks prior to first dose of VRd
* Participant must not require continuous supplemental oxygen
* Hepatitis B infection
* Hepatitis C infection
* Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
* Any therapy that is targeted to B-cell maturation antigen (BCMA)

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to 4 years and 5 months
Secondary outcomes:
measure: Sustained Minimal Residual Disease (MRD) Negative CR
timeFrame: Up to 12 years and 5 months
measure: MRD Negative CR at 9 Months
timeFrame: 9 months
measure: Overall MRD Negative CR
timeFrame: Up to 12 years and 5 months
measure: Overall Survival (OS)
timeFrame: Up to 12 years and 5 months
measure: Complete Response or Better
timeFrame: Up to 12 years and 5 months
measure: Time to Subsequent Anti-myeloma Therapy
timeFrame: Up to 12 years and 5 months
measure: Progression Free Survival on Next-line Therapy (PFS2)
timeFrame: Up to 12 years and 5 months
measure: Number of Participants with Adverse Events (AEs), Abnormalities in Laboratory Parameters, 12-Lead Electrocardiogram (ECG), Physical Examination, and Vital Signs
timeFrame: Up to 12 years and 5 months
measure: Arm B: Systemic Cytokine Concentrations
timeFrame: Up to Day 112
measure: Arm B: Levels of Chimeric Antigen Receptor T cell (CAR-T) Cell Activation Markers
timeFrame: Up to 12 years and 5 months
measure: Arm B: Levels of Soluble B-cell Maturation Antigen (BCMA)
timeFrame: Up to 1 year
measure: Arm B: Levels of Cilta-cel Expansion (proliferation), and Persistence
timeFrame: Up to 12 years and 5 months
measure: Arm B: Number of Participants with Anti-cilta-cel Antibodies
timeFrame: Up to 12 years and 5 months
measure: Arm B: Number of Participants with Presence of Replication Competent Lentivirus
timeFrame: Up to 12 years and 5 months
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: Baseline up to 12 years and 5 months
measure: Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score
timeFrame: Baseline up to 12 years and 5 months
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 Score
timeFrame: Baseline up to 12 years and 5 months
measure: Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score
timeFrame: Baseline up to 12 years and 5 months
measure: Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Items
timeFrame: Up to 161 days
measure: Time to Worsening of Symptoms, Functioning and Overall Well-being
timeFrame: Up to 12 year and 5 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Miami
country: United States
facility: University of Miami Health System
state: Florida
city: Orlando
country: United States
facility: AdventHealth Cancer Institute
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: University Of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian-Weill Cornell Medical College
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Milwaukee
country: United States
facility: Medical College Of Wisconsin
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital Aleman
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Cordoba
country: Argentina
facility: Hospital Privado Universitario De Cordoba
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
city: Heidelberg
country: Australia
facility: Austin Health
city: Herston
country: Australia
facility: Royal Brisbane and Womens Hospital
city: Melbourne
country: Australia
facility: Alfred Health
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: Western Sydney Local Health District
city: Graz
country: Austria
facility: Medizinische Universität Graz, LKH-Univ.Klinikum Graz, Klinische Abteilung für Hämatologie
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen Linz
city: Salzburg
country: Austria
facility: LKH - Universitätsklinikum der PMU Salzburg
city: Vienna
country: Austria
facility: Medical University of Vienna Universitatsklinik fur Innere Medizin I
city: Antwerp
country: Belgium
facility: Universitair Ziekenhuis - Antwerpen
city: Brugge
country: Belgium
facility: AZ St.-Jan Brugge-Oostende AV
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
city: Salvador
country: Brazil
facility: Hospital Sao Rafael
city: Sao Paulo
country: Brazil
facility: Fundacao Antonio Prudente A C Camargo Cancer Center
city: Sao Paulo
country: Brazil
facility: Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
city: Calgary
country: Canada
facility: Arthur J E Child Comprehensive Cancer Centre
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve Rosemont
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Ostrava - Poruba
country: Czechia
facility: Fakultni Nemocnice Ostrava
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Aarhus C
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Lille Cedex
country: France
facility: Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez
city: Nantes
country: France
facility: C.H.U. Hotel Dieu - France
city: Paris cedex 10
country: France
facility: Hopital Saint Louis
city: Poitiers
country: France
facility: CHU Poitiers - Hopital la Miletrie
city: Toulouse cedex 9
country: France
facility: Institut Universitaire du cancer de Toulouse-Oncopole
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg Eppendorf
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Mainz
country: Germany
facility: Universitatsmedizin der Johannes Gutenberg Universitat Mainz
city: München
country: Germany
facility: Klinikum Großhadern der Ludwig-Maximilians-Universität
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg
city: Tubingen
country: Germany
facility: Klinikum der Eberhard Karls Universitaet Abt fur innere Med II Haematologie Onkologie Germany
city: Wuerzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens
city: Athens
country: Greece
facility: Attikon University General Hospital of Attica
city: Thessaloniki
country: Greece
facility: G.Papanikolaou
city: Budapest
country: Hungary
facility: Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Dublin
country: Ireland
facility: St James Hospital
city: Jerusalem
country: Israel
facility: Hadassah University Hospita Ein Kerem
city: Ramat Gan
country: Israel
facility: Sheba Medical Center Tel Hashomer
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Bunkyo Ku
country: Japan
facility: Juntendo University Hospital
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Hyôgo
country: Japan
facility: Hyogo Medical University Hospital
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Kyoto
country: Japan
facility: University Hospital Kyoto Prefectural University of Medicine
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Sendai
country: Japan
facility: Tohoku University Hospital
city: Shibuya
country: Japan
facility: Japanese Red Cross Medical Center
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Nijmegen
country: Netherlands
facility: UMC Radboud
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Oslo
country: Norway
facility: Oslo universitetssykehus HF, Rikshospitalet
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz w Gliwicach
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu
city: Lisboa
country: Portugal
facility: Instituto Portugues de Oncologia
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia
city: Barcelona
country: Spain
facility: Hosp. de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: L'Hospitalet de Llobregat
country: Spain
facility: Instituto Catalan Deoncologia Hospital Duran I Reynals
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Murcia
country: Spain
facility: Hosp. Univ. Virgen de La Arrixaca
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Valencia
country: Spain
facility: Hosp. Univ. I Politecni La Fe
city: Goteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Linköping
country: Sweden
facility: Universitetssjukhuset
city: Lund
country: Sweden
facility: Skane University Hospital
city: Basel
country: Switzerland
facility: Universitatsspital Basel
city: Bern
country: Switzerland
facility: Inselspital Universitatsspital Bern
city: St. Gallen
country: Switzerland
facility: Kantonsspital St Gallen
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Trust,
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
city: Surrey
country: United Kingdom
facility: The Royal Marsden NHS Trust Sutton
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: