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

NCT ID: NCT04923893

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 743 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-19
• Study Completion Date: 2036-09-22

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.

Conditions

Multiple Myeloma

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Bortezomib will be administered SC.

Dexamethasone

Intervention Type: DRUG

Dexamethasone will be administered orally.

Lenalidomide

Intervention Type: DRUG

Lenalidomide will be administered orally.

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).

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Bortezomib will be administered SC.

Dexamethasone

Intervention Type: DRUG

Dexamethasone will be administered orally.

Lenalidomide

Intervention Type: DRUG

Lenalidomide will be administered orally.

Cilta-cel

Intervention Type: DRUG

Cilta-cel infusion will be administered.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide will be administered intravenously.

Fludarabine

Intervention Type: DRUG

Fludarabine will be administered intravenously.

Interventions

Bortezomib

Bortezomib will be administered SC.

Intervention Type: DRUG

Dexamethasone

Dexamethasone will be administered orally.

Intervention Type: DRUG

Lenalidomide

Lenalidomide will be administered orally.

Intervention Type: DRUG

Cilta-cel

Cilta-cel infusion will be administered.

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide will be administered intravenously.

Intervention Type: DRUG

Fludarabine

Fludarabine will be administered intravenously.

Intervention Type: DRUG

Other Intervention Names

JNJ-68284528

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

UCSF

San Francisco, California, United States

Yale Cancer Center

New Haven, Connecticut, United States

University of Miami Health System

Miami, Florida, United States

AdventHealth Cancer Institute

Orlando, Florida, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kentucky

Lexington, Kentucky, United States

Norton Cancer Institute

Louisville, Kentucky, United States

University Of Maryland Medical Center

Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Henry Ford Cancer Institute

Detroit, Michigan, United States

Columbia University Medical Center

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

New York Presbyterian-Weill Cornell Medical College

New York, New York, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

University of Virginia

Charlottesville, Virginia, United States

Medical College Of Wisconsin

Milwaukee, Wisconsin, United States

Hospital Aleman

Buenos Aires, , Argentina

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Hospital Privado Universitario De Cordoba

Córdoba, , Argentina

Royal Prince Alfred Hospital

Camperdown, , Australia

St Vincents Hospital Melbourne

Fitzroy, , Australia

Austin Health

Heidelberg, , Australia

Royal Brisbane and Womens Hospital

Herston, , Australia

Alfred Health

Melbourne, , Australia

Peter MacCallum Cancer Centre

Melbourne, , Australia

Fiona Stanley Hospital

Murdoch, , Australia

Calvary Mater Newcastle Hospital

Waratah, , Australia

Western Sydney Local Health District

Westmead, , Australia

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

Graz, , Austria

Krankenhaus der Elisabethinen Linz

Linz, , Austria

LKH - Universitätsklinikum der PMU Salzburg

Salzburg, , Austria

Medical University of Vienna Universitatsklinik fur Innere Medizin I

Vienna, , Austria

Universitair Ziekenhuis - Antwerpen

Antwerp, , Belgium

AZ St.-Jan Brugge-Oostende AV

Bruges, , Belgium

UZ Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman

Liège, , Belgium

Hospital Sao Rafael

Salvador, , Brazil

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, , Brazil

Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein

São Paulo, , Brazil

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Princess Margaret Cancer Centre University Health Network

Toronto, Ontario, Canada

Hopital Maisonneuve Rosemont

Montreal, Quebec, Canada

Fakultni nemocnice Brno

Brno, , Czechia

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Fakultni Nemocnice Ostrava

Ostrava - Poruba, , Czechia

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Aarhus University Hospital

Aarhus C, , Denmark

Rigshospitalet

Copenhagen, , Denmark

Odense Universitetshospital

Odense C, , Denmark

Helsinki University Hospital

Helsinki, , Finland

Oulu University Hospital

Oulu, , Finland

Turku University Hospital

Turku, , Finland

Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez

Lille, , France

C.H.U. Hotel Dieu - France

Nantes, , France

Hopital Saint Louis

Paris, , France

CHU Poitiers - Hopital la Miletrie

Poitiers, , France

Institut Universitaire du cancer de Toulouse-Oncopole

Toulouse, , France

Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin

Berlin, , Germany

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, , Germany

Universitatsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitaetsklinikum Hamburg Eppendorf

Hamburg, , Germany

Universitaetsklinikum Heidelberg

Heidelberg, , Germany

Universitaetsklinikum Leipzig

Leipzig, , Germany

Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Mainz, , Germany

Klinikum Großhadern der Ludwig-Maximilians-Universität

München, , Germany

Universitaetsklinikum Regensburg

Regensburg, , Germany

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

Tübingen, , Germany

Universitatsklinikum Wurzburg

Würzburg, , Germany

Alexandra General Hospital of Athens

Athens, , Greece

Attikon University General Hospital of Attica

Athens, , Greece

G.Papanikolaou

Thessaloniki, , Greece

Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely

Budapest, , Hungary

Debreceni Egyetem Klinikai Kozpont

Debrecen, , Hungary

St James Hospital

Dublin, , Ireland

Hadassah University Hospita Ein Kerem

Jerusalem, , Israel

Sheba Medical Center Tel Hashomer

Ramat Gan, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Juntendo University Hospital

Bunkyō City, , Japan

Kyushu University Hospital

Fukuoka, , Japan

Hyogo Medical University Hospital

Hyôgo, , Japan

Kanazawa University Hospital

Kanazawa, , Japan

University Hospital Kyoto Prefectural University of Medicine

Kyoto, , Japan

Nagoya City University Hospital

Nagoya, , Japan

Okayama University Hospital

Okayama, , Japan

Hokkaido University Hospital

Sapporo, , Japan

Tohoku University Hospital

Sendai, , Japan

Japanese Red Cross Medical Center

Shibuya City, , Japan

VU Medisch Centrum

Amsterdam, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

UMC Radboud

Nijmegen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Oslo universitetssykehus HF, Rikshospitalet

Oslo, , Norway

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

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

Gliwice, , Poland

Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli

Lublin, , Poland

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, , Poland

Instytut Hematologii i Transfuzjologii

Warsaw, , Poland

Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, , Poland

Instituto Portugues de Oncologia

Lisbon, , Portugal

Instituto Portugues de Oncologia

Porto, , Portugal

Chonnam National University Hwasun Hospital

Jeollanam-do, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea Seoul St Marys Hospital

Seoul, , South Korea

Hosp. de La Santa Creu I Sant Pau

Barcelona, , Spain

Hosp Univ Vall D Hebron

Barcelona, , Spain

Instituto Catalan Deoncologia Hospital Duran I Reynals

L'Hospitalet de Llobregat, , Spain

Hosp. Gral. Univ. Gregorio Maranon

Madrid, , Spain

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Hosp. Univ. Virgen de La Arrixaca

Murcia, , Spain

Clinica Univ. de Navarra

Pamplona, , Spain

Hosp Clinico Univ de Salamanca

Salamanca, , Spain

Hosp. Univ. Marques de Valdecilla

Santander, , Spain

Hosp. Virgen Del Rocio

Seville, , Spain

Hosp. Univ. I Politecni La Fe

Valencia, , Spain

Sahlgrenska University Hospital

Gothenburg, , Sweden

Universitetssjukhuset

Linköping, , Sweden

Skane University Hospital

Lund, , Sweden

Universitatsspital Basel

Basel, , Switzerland

Inselspital Universitatsspital Bern

Bern, , Switzerland

Kantonsspital St Gallen

Sankt Gallen, , Switzerland

University Hospitals Birmingham NHS Trust,

Birmingham, , United Kingdom

Bristol Royal Infirmary

Bristol, , United Kingdom

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

University College Hospital

London, , United Kingdom

Kings College Hospital

London, , United Kingdom

Manchester Royal Infirmary

Manchester, , United Kingdom

The Royal Marsden NHS Trust Sutton

Surrey, , United Kingdom

Countries

Italy; United States; Argentina; Australia; Austria; Belgium; Brazil; Canada; Czechia; Denmark; Finland; France; Germany; Greece; Hungary; Ireland; Israel; Japan; Netherlands; Norway; Poland; Portugal; South Korea; Spain; Sweden; Switzerland; United Kingdom

Related Links

https://sparkcures.com/trial/1182/nct04923893?utm_source=ctgov&utm_medium=organic&utm_campaign=cartitude5

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

Other Identifiers

68284528MMY3004

Identifier Type: OTHER

Identifier Source: secondary_id

2021-001242-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-505850-16-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR109015

Identifier Type: -

Identifier Source: org_study_id