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 (CARTITUDE-5)

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

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).

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bortezomib; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Cilta-cel; Drug: Cyclophosphamide; Drug: Fludarabine

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.

• Study Type: Interventional
• Enrollment (Estimated): 650
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: SparkCures Patient Support (US only); Phone Number: (888) 676-2873; Email: support+nct@sparkcures.com
• Study Contact Backup: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1118AAT
    • Recruiting
    • Hospital Aleman
  • Buenos Aires, Argentina, C1199ABD
    • Recruiting
    • Hospital Italiano de Buenos Aires
  • Cordoba, Argentina, X5016KEH
    • Recruiting
    • Hospital Privado Centro Medico de Cordoba
• Australia
  • Camperdown, Australia, 2050
    • Active, not recruiting
    • Royal Prince Alfred Hospital
  • Fitzroy, Australia, 3065
    • Active, not recruiting
    • St. Vincent's Hospital Melbourne
  • Heidelberg, Australia, 3084
    • Active, not recruiting
    • Austin Health
  • Herston, Australia, 4029
    • Active, not recruiting
    • Royal Brisbane and Womens Hospital
  • Melbourne, Australia, 3004
    • Active, not recruiting
    • Alfred Health
  • Melbourne, Australia, 8006
    • Active, not recruiting
    • Peter MacCallum Cancer Centre
  • Murdoch, Australia, 6150
    • Active, not recruiting
    • Fiona Stanley Hospital
  • Waratah, Australia, 2298
    • Active, not recruiting
    • Calvary Mater Newcastle Hospital
  • Westmead, Australia, 2145
    • Active, not recruiting
    • Western Sydney Local Health District
• Austria
  • Graz, Austria, 8036
    • Completed
    • Medizinische Universität Graz, LKH-Univ.Klinikum Graz, Klinische Abteilung für Hämatologie
  • Linz, Austria, 4020
    • Active, not recruiting
    • Krankenhaus der Elisabethinen Linz
  • Salzburg, Austria, 5020
    • Active, not recruiting
    • LKH - Universitätsklinikum der PMU Salzburg
  • Vienna, Austria, 1090
    • Active, not recruiting
    • Medical University of Vienna,Universitätsklinik für Innere Medizin I
• Belgium
  • Antwerp, Belgium, 2650
    • Active, not recruiting
    • Universitair Ziekenhuis - Antwerpen
  • Brugge, Belgium, 8000
    • Active, not recruiting
    • AZ St.-Jan Brugge-Oostende AV
  • Gent, Belgium, 9000
    • Completed
    • UZ Gent
  • Leuven, Belgium, 3000
    • Completed
    • UZ Leuven
  • Liege, Belgium, B-4000
    • Completed
    • Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
• Brazil
  • Salvador, Brazil, 41253-190
    • Active, not recruiting
    • Hospital Sao Rafael
  • Sao Paulo, Brazil, 01509 900
    • Active, not recruiting
    • Fundacao Antonio Prudente A C Camargo Cancer Center
  • São Paulo, Brazil, 05652-900
    • Active, not recruiting
    • Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Active, not recruiting
      • Tom Baker Cancer Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Active, not recruiting
      • Vancouver General Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8V5C2
      • Active, not recruiting
      • Juravinski Cancer Centre
    • Toronto, Ontario, Canada, M5G2M9
      • Active, not recruiting
      • Princess Margaret Cancer Centre University Health Network
  • Quebec
    • Montréal, Quebec, Canada, H1T 2M4
      • Active, not recruiting
      • Hôpital Maisonneuve-Rosemont
• Czechia
  • Brno, Czechia, 625 00
    • Recruiting
    • Fakultní Nemocnice Brno
  • Hradec Kralove, Czechia, 500 05
    • Recruiting
    • Fakultni nemocnice Hradec Kralove
  • Ostrava - Poruba, Czechia, 708 52
    • Recruiting
    • Fakultni nemocnice Ostrava
  • Praha 2, Czechia, 128 08
    • Recruiting
    • Vseobecna fakultni nemocnice v Praze
• Denmark
  • Aarhus C, Denmark, 8000
    • Recruiting
    • Aarhus University Hospital
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
  • Odense C, Denmark, 5000
    • Recruiting
    • Odense Universitetshospital
• Finland
  • Helsinki, Finland, 00029 HUS
    • Active, not recruiting
    • Helsinki University Hospital
  • Oulu, Finland, 90220
    • Active, not recruiting
    • Oulu University Hospital
  • Turku, Finland, 20520
    • Active, not recruiting
    • Turku University Hospital
• France
  • Lille Cedex, France, 59000
    • Active, not recruiting
    • Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez
  • Nantes, France, 44093
    • Completed
    • C.H.U. Hotel Dieu - France
  • Paris cedex 10, France, 75475
    • Active, not recruiting
    • Hopital Saint Louis
  • Poitiers, France, 86021
    • Active, not recruiting
    • CHU Poitiers - Hôpital la Milétrie
  • Toulouse cedex 9, France, 31059
    • Active, not recruiting
    • Institut Universitaire du Cancer de Toulouse-Oncopole
• Germany
  • Berlin, Germany, 12203
    • Active, not recruiting
    • Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin
  • Dresden, Germany, 01307
    • Active, not recruiting
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Freiburg, Germany, 79106
    • Active, not recruiting
    • Universitätsklinikum Freiburg
  • Hamburg, Germany, 20246
    • Active, not recruiting
    • Universitaetsklinikum Hamburg Eppendorf
  • Heidelberg, Germany, 69120
    • Active, not recruiting
    • Universitaetsklinikum Heidelberg
  • Leipzig, Germany, 04103
    • Active, not recruiting
    • Universitaetsklinikum Leipzig
  • Mainz, Germany, 55131
    • Active, not recruiting
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • München, Germany, 81377
    • Active, not recruiting
    • Klinikum Großhadern der Ludwig-Maximilians-Universität
  • Regensburg, Germany, 93053
    • Active, not recruiting
    • Universitaetsklinikum Regensburg
  • Tubingen, Germany, 72076
    • Active, not recruiting
    • Klinikum der Eberhard Karls Universitaet Abt fur innere Med II Haematologie Onkologie Germany
  • Wuerzburg, Germany, 97080
    • Active, not recruiting
    • Universitätsklinikum Würzburg
• Greece
  • Athens, Greece, 12462
    • Active, not recruiting
    • Attikon University General Hospital of Attica
  • Athens, Greece, 11528
    • Active, not recruiting
    • Alexandra General Hospital of Athens
  • Thessaloniki, Greece, 57010
    • Active, not recruiting
    • G.Papanikolaou
• Hungary
  • Budapest, Hungary, 1097
    • Recruiting
    • Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet, Szent László Telephely
  • Debrecen, Hungary, 4032
    • Recruiting
    • Debreceni Egyetem Klinikai Kozpont
• Ireland
  • Dublin, Ireland, D08 NHY1
    • Recruiting
    • St James Hospital
• Israel
  • Jerusalem, Israel, P.O.B. 12000
    • Recruiting
    • Hadassah University Hospita - Ein Kerem
  • Ramat Gan, Israel, 52621
    • Recruiting
    • Sheba Medical Center Tel Hashomer
  • Tel Aviv, Israel, 64239
    • Recruiting
    • Tel Aviv Sourasky Medical Center
• Japan
  • Bunkyo-Ku, Japan, 113-8431
    • Active, not recruiting
    • Juntendo University Hospital
  • Fukuoka, Japan, 812-8582
    • Active, not recruiting
    • Kyushu University Hospital
  • Hyôgo, Japan, 663-8501
    • Active, not recruiting
    • Hyogo Medical University Hospital
  • Kanazawa, Japan, 920-8641
    • Active, not recruiting
    • Kanazawa University Hospital
  • Kyoto, Japan, 602-8566
    • Active, not recruiting
    • University Hospital Kyoto Perfectural University of Medicine
  • Nagoya, Japan, 467 8602
    • Completed
    • Nagoya City University Hospital
  • Okayama, Japan, 700-8558
    • Active, not recruiting
    • Okayama University Hospital
  • Sapporo, Japan, 060-8648
    • Active, not recruiting
    • Hokkaido University Hospital
  • Sendai, Japan, 980-8574
    • Active, not recruiting
    • Tohoku University Hospital
  • Shibuya, Japan, 150-8935
    • Active, not recruiting
    • Japanese Red Cross Medical Center
• Korea, Republic of
  • Jeollanam-do, Korea, Republic of, 58128
    • Active, not recruiting
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of, 03080
    • Active, not recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Active, not recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Active, not recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Active, not recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Active, not recruiting
    • The Catholic University of Korea Seoul St. Mary'S Hospital
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Completed
    • VU Medisch Centrum
  • Groningen, Netherlands, 9713 GZ
    • Active, not recruiting
    • University Medical Center Groningen
  • Nijmegen, Netherlands, 6500 HB
    • Active, not recruiting
    • UMC Radboud
  • Rotterdam, Netherlands, 3075 EA
    • Active, not recruiting
    • Erasmus MC
• Norway
  • Oslo, Norway, 0372
    • Active, not recruiting
    • Oslo Universitetssykehus HF, Rikshospitalet
• Poland
  • Gdansk, Poland, 80-214
    • Active, not recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Gliwice, Poland, 44102
    • Active, not recruiting
    • Narodowy Instytut Onkologii im.Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz. w Gliwicach
  • Lublin, Poland, 20-090
    • Active, not recruiting
    • Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli
  • Poznan, Poland, 60-569
    • Active, not recruiting
    • Uniwersytecki Szpital Kliniczny w Poznaniu
  • Warszawa, Poland, 02-776
    • Active, not recruiting
    • Instytut Hematologii i Transfuzjologii
  • Wroclaw, Poland, 52-007
    • Active, not recruiting
    • Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
• Portugal
  • Lisboa, Portugal, 1099-023
    • Active, not recruiting
    • Instituto Português de Oncologia
  • Porto, Portugal, 4200072
    • Active, not recruiting
    • Instituto Português de Oncologia
• Spain
  • Barcelona, Spain, 8035
    • Active, not recruiting
    • Hosp. Univ. Vall D Hebron
  • Barcelona, Spain, 08025
    • Active, not recruiting
    • Hosp. de La Santa Creu I Sant Pau
  • L'Hospitalet de Llobregat, Spain, 08908
    • Active, not recruiting
    • Instituto Catalan Deoncologia Hospital Duran I Reynals
  • Madrid, Spain, 28041
    • Active, not recruiting
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28007
    • Active, not recruiting
    • Hosp. Gral. Univ. Gregorio Maranon
  • Murcia, Spain, 30120
    • Active, not recruiting
    • Hosp. Univ. Virgen de La Arrixaca
  • Pamplona, Spain, 31008
    • Active, not recruiting
    • Clinica Univ. de Navarra
  • Salamanca, Spain, 37007
    • Active, not recruiting
    • Hosp. Clinico Univ. de Salamanca
  • Santander, Spain, 39008
    • Active, not recruiting
    • Hosp. Univ. Marques de Valdecilla
  • Sevilla, Spain, 41013
    • Active, not recruiting
    • Hosp. Virgen Del Rocio
  • Valencia, Spain, 46026
    • Active, not recruiting
    • Hosp. Univ. I Politecni La Fe
• Sweden
  • Goteborg, Sweden, 413 45
    • Completed
    • Sahlgrenska University hospital
  • Linköping, Sweden, 58185
    • Recruiting
    • Universitetssjukhuset
  • Lund, Sweden, 221 85
    • Recruiting
    • Skåne University Hospital
• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • Universitätsspital Basel
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital, Universitätsspital Bern
  • St. Gallen, Switzerland, 9007
    • Recruiting
    • Kantonsspital St.Gallen
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Active, not recruiting
    • University Hospitals Birmingham NHS Trust,
  • Bristol, United Kingdom, BS2 8BJ
    • Active, not recruiting
    • Bristol Royal Infirmary
  • Leeds,, United Kingdom, LS9 7TF
    • Active, not recruiting
    • Leeds Teaching Hospitals NHS Trust
  • London, United Kingdom, NW1 2BU
    • Active, not recruiting
    • University College Hospital
  • London, United Kingdom, SE5 9RS
    • Active, not recruiting
    • King's College Hospital
  • Manchester, United Kingdom, M13 9WL
    • Active, not recruiting
    • Manchester Royal Infirmary
  • Surrey, United Kingdom, SM2 5PT
    • Active, not recruiting
    • The Royal Marsden NHS Trust Sutton
• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • UCSF
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Health System
    • Orlando, Florida, United States, 32832
      • Recruiting
      • AdventHealth Cancer Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals & Clinics
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0293
      • Completed
      • University of Kentucky
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Cancer Institute
  • Maryland
    • Baltimore, Maryland, United States, 21201-1595
      • Recruiting
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48202-2608
      • Recruiting
      • Henry Ford Cancer Institute
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10065
      • Recruiting
      • New York Presbyterian-Weill Cornell Medical College
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • University of Pittsburgh Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel); Participants will receive VRd regimen for 6 cycles before randomization. Following randomization, participants in Arm B will undergo apheresis and receive two more cycles of VRd as bridging therapy. In VRd treatment, participants will receive bortezomib 1.3 mg/m^2 SC on Days 1, 4, 8 and 11 of each cycle for Cycles 1 to 8; oral lenalidomide 25 mg on days 1 to 14 of each cycle for Cycles 1 to 8 and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle for Cycles 1 to 8. Each cycle will consist of 21 days. After 8 cycles of VRd, participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg).	Drug: Bortezomib; Bortezomib will be administered SC.; Drug: Dexamethasone; Dexamethasone will be administered orally.; Drug: Lenalidomide; Lenalidomide will be administered orally.; Drug: Cilta-cel; Cilta-cel infusion will be administered.; Other Names: JNJ-68284528; Drug: Cyclophosphamide; Cyclophosphamide will be administered intravenously.; Drug: Fludarabine; Fludarabine will be administered intravenously.
Experimental: Arm A: VRd+Rd (Standard Therapy); Participants will receive bortezomib, lenalidomide, and dexamethasone (VRd) regimen for 6 cycles before randomization. Following randomization, participants in Arm A will receive 2 more cycles of VRd. In VRd treatment, participants will receive bortezomib 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8 and 11 of each cycle (Cycles 1 to 8), oral lenalidomide 25 mg on Days 1 to 14 of each cycle (Cycles 1 to 8) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle (Cycles 1 to 8). Each cycle will consist of 21 days. After 8 cycles of VRd, treatment will continue with lenalidomide and dexamethasone (Rd) maintenance therapy. In Rd treatment, participants will receive oral lenalidomide 25 mg on Days 1 to 21 of each cycle and oral dexamethasone 40 mg on Days 1, 8, 15, and 22 of each cycle. Each cycle will consist of 28 days. Participants will continue to receive Rd until confirmed progressive disease or unacceptable toxicity.	Drug: Bortezomib; Bortezomib will be administered SC.; Drug: Dexamethasone; Dexamethasone will be administered orally.; Drug: Lenalidomide; Lenalidomide will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression-free survival is defined as the time from the date of randomization to the date of first documented Progressive Disease (PD), as defined in the International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first.	Up to 4 years and 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Minimal Residual Disease (MRD) Negative CR	Sustained MRD negative complete response (CR) as determined by next generation sequencing (NGS) with sensitivity of 10^-5, and defined by MRD negative CR plus at least 12 months durability of the MRD negative CR status.	Up to 12 years and 5 months
MRD Negative CR at 9 Months	MRD negative CR rate at 9 months is defined as the percentage of participants who achieve MRD negative CR status at 9±3 months after the randomization date.	9 months
Overall MRD Negative CR	Overall MRD negative is defined as the percentage of participants who achieve MRD negativity at any time after the date of randomization before initiation of subsequent therapy.	Up to 12 years and 5 months
Overall Survival (OS)	Overall survival is measured from the date of randomization to the date of the participant's death.	Up to 12 years and 5 months
Complete Response or Better	CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response according to the IMWG criteria.	Up to 12 years and 5 months
Time to Subsequent Anti-myeloma Therapy	Time to subsequent anti-myeloma therapy is defined as the time from randomization to the start of subsequent anti-myeloma therapy.	Up to 12 years and 5 months
Progression Free Survival on Next-line Therapy (PFS2)	PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as PD as assessed by investigator that starts after the next line of subsequent therapy, or death from any cause, whichever occurs first.	Up to 12 years and 5 months
Number of Participants with Adverse Events (AEs), Abnormalities in Laboratory Parameters, 12-Lead Electrocardiogram (ECG), Physical Examination, and Vital Signs	Number of participants with AEs, abnormalities in laboratory parameters (complete blood count [CBC] with differential, coagulation, chimeric antigen receptor T cell [CAR-T] chemistry, full metabolic panel etc.), 12-lead ECG, physical examination, and vital signs will be reported.	Up to 12 years and 5 months
Arm B: Systemic Cytokine Concentrations	Serum or plasma proteomic profiling of cytokines (such as interleukin [IL] 6, IL-15, and IL 10) concentrations will be measured for biomarker assessment.	Up to Day 112
Arm B: Levels of Chimeric Antigen Receptor T cell (CAR-T) Cell Activation Markers	CAR-T cell activation markers including, but not limited to, CD4+, CD8+, CD25+, central memory, effector memory cells will be reported. An evaluation of cell populations may be performed by flow cytometry, cytometry by time of flight (CyTOF), single cell RNA sequencing (scRNAseq) or similar technologies and be correlated with response.	Up to 12 years and 5 months
Arm B: Levels of Soluble B-cell Maturation Antigen (BCMA)	Levels of soluble BCMA will be reported.	Up to 1 year
Arm B: Levels of Cilta-cel Expansion (proliferation), and Persistence	Levels of cilta-cel expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.	Up to 12 years and 5 months
Arm B: Number of Participants with Anti-cilta-cel Antibodies	Number of participants with anti-cilta-cel antibodies will be reported.	Up to 12 years and 5 months
Arm B: Number of Participants with Presence of Replication Competent Lentivirus	Number of participants with presence of replication competent lentivirus will be reported.	Up to 12 years and 5 months
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	The EORTC QLQ-C30 includes 30 items in 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The responses are reported using a verbal rating scale. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.	Baseline up to 12 years and 5 months
Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score	The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items with recall period of "7 days" and responses are reported on a 5-point verbal rating scale. Item responses are scored from 0 to 4. Higher scores indicate greater severity/impact.	Baseline up to 12 years and 5 months
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	The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems, where Level 1: no problem, Level 2: slight problems, Level 3: moderate problems, Level 4: severe problems and Level 5: extreme problems, plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).	Baseline up to 12 years and 5 months
Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score	The PGIS uses 2 items to assess the participant's perception of the severity of their disease symptoms and impact using a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).	Baseline up to 12 years and 5 months
Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Items	The National Cancer Institute's PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference that ranges from 0 to 4 with higher scores indicating higher frequency or greater severity/impact.	Up to 161 days
Time to Worsening of Symptoms, Functioning and Overall Well-being	Time to worsening is measured as the interval from the date of randomization to the start date of worsening in MySIm-Q symptom, impact, or total scores.	Up to 12 year and 5 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

Helpful Links

• Click here to learn more about the 68284528MMY3004 (CARTITUDE-5) trial (US only)

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2021
• Primary Completion (Estimated): June 11, 2026
• Study Completion (Estimated): December 13, 2034

Study Registration Dates

• First Submitted: June 10, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Cellular Therapy; BCMA CAR-T; Newly Diagnosed Multiple Myeloma; CAR-T Therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Cyclophosphamide; Lenalidomide; Bortezomib; Fludarabine
• Other Study ID Numbers: CR109015; 2021-001242-35 (EudraCT Number); 68284528MMY3004 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No