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

NCT04923893 | Active Not Recruiting Phase 3 DMC FDA Drug

• 4 other identifiers: CR10901568284528MMY30042021-001242-352023-505850-16-00
• Study Type: interventional
• Target: 743
• Locations: 25 countries
• Sites: 127

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).

Conditions

Multiple Myeloma

Keywords

Newly Diagnosed Multiple Myeloma; Cellular Therapy; CAR-T Therapy; BCMA CAR-T

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (20)

• Sustained Minimal Residual Disease (MRD) Negative CR

  Up to 12 years and 5 months

• MRD Negative CR at 9 Months

  9 months

• Overall MRD Negative CR

  Up to 12 years and 5 months

• Overall Survival (OS)

  Up to 12 years and 5 months

• Complete Response or Better

  Up to 12 years and 5 months

Study Arms (2)

Arm A: VRd+Rd (Standard Therapy)

EXPERIMENTAL

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; Drug: Dexamethasone; Drug: Lenalidomide

Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel)

EXPERIMENTAL

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; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Cilta-cel; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Bortezomib DRUG

Bortezomib will be administered SC.

Arm A: VRd+Rd (Standard Therapy); Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel)

Dexamethasone DRUG

Dexamethasone will be administered orally.

Arm A: VRd+Rd (Standard Therapy); Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel)

Lenalidomide DRUG

Lenalidomide will be administered orally.

Arm A: VRd+Rd (Standard Therapy); Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel)

Cilta-cel DRUG

Cilta-cel infusion will be administered.

Also known as: JNJ-68284528

Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel)

Cyclophosphamide DRUG

Cyclophosphamide will be administered intravenously.

Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel)

Fludarabine DRUG

Fludarabine will be administered intravenously.

Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (136)

UCSF

San Francisco, California, 94143, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

University of Miami Health System

Miami, Florida, 33136, United States

Location

AdventHealth Cancer Institute

Orlando, Florida, 32832, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kentucky

Lexington, Kentucky, 40536-0293, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

University Of Maryland Medical Center

Baltimore, Maryland, 21201-1595, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Cancer Institute

Detroit, Michigan, 48202-2608, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

New York Presbyterian-Weill Cornell Medical College

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Medical College Of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hospital Aleman

Buenos Aires, C1118AAT, Argentina

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1199ABD, Argentina

Location

Hospital Privado Universitario De Cordoba

Córdoba, 5016, Argentina

Location

Royal Prince Alfred Hospital

Camperdown, 2050, Australia

Location

St Vincents Hospital Melbourne

Fitzroy, 3065, Australia

Location

Austin Health

Heidelberg, 3084, Australia

Location

Royal Brisbane and Womens Hospital

Herston, 4029, Australia

Location

Alfred Health

Melbourne, 3004, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, 8006, Australia

Location

Fiona Stanley Hospital

Murdoch, 6150, Australia

Location

Calvary Mater Newcastle Hospital

Waratah, 2298, Australia

Location

Western Sydney Local Health District

Westmead, 2145, Australia

Location

Medizinische Universitat Graz, LKH-Univ.Klinikum Graz, Klinische Abteilung für Hämatologie

Graz, 8036, Austria

Location

Krankenhaus der Elisabethinen Linz

Linz, 4020, Austria

Location

LKH - Universitätsklinikum der PMU Salzburg

Salzburg, 5020, Austria

Location

Medical University of Vienna Universitatsklinik fur Innere Medizin I

Vienna, 1090, Austria

Location

Universitair Ziekenhuis - Antwerpen

Antwerp, 2650, Belgium

Location

AZ St.-Jan Brugge-Oostende AV

Bruges, 8000, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman

Liège, B-4000, Belgium

Location

Hospital Sao Rafael

Salvador, 41253-190, Brazil

Location

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, 01509 900, Brazil

Location

Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein

São Paulo, 05652 900, Brazil

Location

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V5C2, Canada

Location

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, M5G2M9, Canada

Location

Hopital Maisonneuve Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Fakultni nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Fakultni Nemocnice Ostrava

Ostrava - Poruba, 708 52, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 08, Czechia

Location

Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Odense Universitetshospital

Odense C, 5000, Denmark

Location

Helsinki University Hospital

Helsinki, 00290, Finland

Location

Oulu University Hospital

Oulu, 90220, Finland

Location

Turku University Hospital

Turku, 20520, Finland

Location

Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez

Lille, 59000, France

Location

C.H.U. Hotel Dieu - France

Nantes, 44093, France

Location

Hopital Saint Louis

Paris, 75475, France

Location

CHU Poitiers - Hopital la Miletrie

Poitiers, 86021, France

Location

Institut Universitaire du cancer de Toulouse-Oncopole

Toulouse, 31059, France

Location

Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin

Berlin, 12203, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, 01307, Germany

Location

Universitatsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitaetsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Mainz, 55131, Germany

Location

Klinikum Großhadern der Ludwig-Maximilians-Universität

München, 81377, Germany

Location

Universitaetsklinikum Regensburg

Regensburg, 93053, Germany

Location

Klinikum der Eberhard Karls Universitaet Abt fur innere Med II Haematologie Onkologie Germany

Tübingen, 72076, Germany

Location

Universitatsklinikum Wurzburg

Würzburg, 97080, Germany

Location

Alexandra General Hospital of Athens

Athens, 11528, Greece

Location

Attikon University General Hospital of Attica

Athens, 12462, Greece

Location

G.Papanikolaou

Thessaloniki, 57010, Greece

Location

Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely

Budapest, 1097, Hungary

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

St James Hospital

Dublin, D08 NHY1, Ireland

Location

Hadassah University Hospita Ein Kerem

Jerusalem, P.O.B. 12000, Israel

Location

Sheba Medical Center Tel Hashomer

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Juntendo University Hospital

Bunkyō City, 113 8431, Japan

Location

Kyushu University Hospital

Fukuoka, 812 8582, Japan

Location

Hyogo Medical University Hospital

Hyôgo, 663-8501, Japan

Location

Kanazawa University Hospital

Kanazawa, 920 8641, Japan

Location

University Hospital Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

Nagoya City University Hospital

Nagoya, 467 8602, Japan

Location

Okayama University Hospital

Okayama, 700 8558, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

Tohoku University Hospital

Sendai, 980 8574, Japan

Location

Japanese Red Cross Medical Center

Shibuya City, 150-8935, Japan

Location

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

UMC Radboud

Nijmegen, 6500 HB, Netherlands

Location

Erasmus MC

Rotterdam, 3075 EA, Netherlands

Location

Oslo universitetssykehus HF, Rikshospitalet

Oslo, 0372, Norway

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80 214, Poland

Location

Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz w Gliwicach

Gliwice, 44102, Poland

Location

Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli

Lublin, 20 090, Poland

Location

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, 60-569, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02 776, Poland

Location

Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, 50 367, Poland

Location

Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.P.E. 1

Lisbon, 1099-023, Portugal

Location

Instituto Portugues de Oncologia do Porto Francisco Gentil, E.P.E.

Porto, 4200072, Portugal

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

The Catholic University of Korea Seoul St Marys Hospital

Seoul, 06591, South Korea

Location

Hosp. de La Santa Creu I Sant Pau

Barcelona, 08025, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 8035, Spain

Location

Instituto Catalan Deoncologia Hospital Duran I Reynals

L'Hospitalet de Llobregat, 08908, Spain

Location

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Univ. Virgen de La Arrixaca

Murcia, 30120, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Hosp. Univ. Marques de Valdecilla

Santander, 39008, Spain

Location

Hosp. Virgen Del Rocio

Seville, 41013, Spain

Location

Hosp. Univ. I Politecni La Fe

Valencia, 46026, Spain

Location

Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

Universitetssjukhuset

Linköping, 58185, Sweden

Location

Skane University Hospital

Lund, 221 85, Sweden

Location

Universitatsspital Basel

Basel, 4031, Switzerland

Location

Inselspital Universitatsspital Bern

Bern, 3010, Switzerland

Location

Kantonsspital St Gallen

Sankt Gallen, 9007, Switzerland

Location

University Hospitals Birmingham NHS Trust,

Birmingham, B15 2TH, United Kingdom

Location

Bristol Royal Infirmary

Bristol, BS2 8BJ, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

Location

University College Hospital

London, NW1 2BU, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

The Royal Marsden NHS Trust Sutton

Surrey, SM2 5PT, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Dexamethasone; Lenalidomide; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 10, 2021
• First Posted: June 11, 2021
• Study Start: August 19, 2021
• Primary Completion (Estimated): February 14, 2029
• Study Completion (Estimated): September 22, 2036
• Last Updated: May 8, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

DK (3); BE (5); NL (4); IE (1); BR (3); HU (2); ES (11); DE (11); JP (10); PL (6); PT (2); IL (3); KR (6); GR (3); GB (7); CH (3); AR (3); US (19); AU (4); FI (3); CA (5); FR (5); NO (1); SE (3); CZ (4)