A Study of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma

NCT ID: NCT05257083

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

759 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-10

Study Completion Date

2040-08-31

Brief Summary

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The purpose of this study is to compare the efficacy of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Ciltacabtagene Autoleucel versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Autologous Stem Cell Transplant (ASCT) in newly diagnosed multiple myeloma patients.

Detailed Description

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

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

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

Conditions

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Multiple Myeloma

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: DVRd + ASCT+DVRd (Standard Therapy)

Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 4 induction cycles. Followed by ASCT and 2 cycles of DVRd consolidation, and lenalidomide maintenance therapy for 2 years

Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.

Bortezomib SC 1.3 mg/m\^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.

Each cycle will consist 28 days.

Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years

Group Type ACTIVE_COMPARATOR

No interventions assigned to this group

Arm B: DVRd followed by Ciltacabtagene Autoleucel

Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles.

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), followed by lenalidomide post CAR-T cell therapy for 2 years

Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.

Bortezomib SC 1.3 mg/m\^2 on days 1, 4, 8, and 11 of each cycle 1-6.

Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6.

Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.

Each cycle will consist of 28 days.

Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

Daratumumab will be administered SC.

Bortezomib

Intervention Type DRUG

Bortezomib will be administered SC.

Lenalidomide

Intervention Type DRUG

Lenalidomide will be administered orally.

Dexamethasone

Intervention Type DRUG

Dexamethasone will be administered orally.

Cilta-cel

Intervention Type DRUG

Cilta-cel will be administered intravenously

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide will be administered intravenously.

Fludarabine

Intervention Type DRUG

Fludarabine will be administered intravenously.

Interventions

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Daratumumab

Daratumumab will be administered SC.

Intervention Type DRUG

Bortezomib

Bortezomib will be administered SC.

Intervention Type DRUG

Lenalidomide

Lenalidomide will be administered orally.

Intervention Type DRUG

Dexamethasone

Dexamethasone will be administered orally.

Intervention Type DRUG

Cilta-cel

Cilta-cel will be administered intravenously

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide will be administered intravenously.

Intervention Type DRUG

Fludarabine

Fludarabine will be administered intravenously.

Intervention Type DRUG

Other Intervention Names

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JNJ-68284528

Eligibility Criteria

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Inclusion Criteria

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

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

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role collaborator

Stichting European Myeloma Network

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Arkansas

Little Rock, Arkansas, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

UC San Diego Health Moores Cancer Center

San Diego, California, United States

Site Status

University of California San Francisco (UCSF)

San Francisco, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

University Of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Boston Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Karmanos Cancer Center

Detroit, Michigan, United States

Site Status

Mount Sinai Medical Venter

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Montefiore M-E Center

The Bronx, New York, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status

Medical College Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Princess Alexandra Hospital

Brisbane, , Australia

Site Status

Royal Prince Alfred Hospital

Camperdown, , Australia

Site Status

Royal Brisbane and Womens Hospital

Herston, , Australia

Site Status

Alfred Health

Melbourne, , Australia

Site Status

Austin Hospital

Melbourne, , Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, , Australia

Site Status

Fiona Stanley Hospital

Murdoch, , Australia

Site Status

Calvary Mater Newcastle Hospital

Waratah, , Australia

Site Status

Westmead Hospital

Westmead, , Australia

Site Status

Jules Bordet Instituut

Anderlecht, , Belgium

Site Status

UZA

Antwerp, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Cross Cancer Institute

Edmonton, , Canada

Site Status

McMaster University

Hamilton, , Canada

Site Status

Hopital Maisonneuve-Rosemont

Montreal, , Canada

Site Status

Mcgill University Health Centre

Montreal, , Canada

Site Status

Ottawa Hospital Research Institute

Ottawa, , Canada

Site Status

(CHU) Centre Hospitalier Universitaire de Quebec Laval

Québec, , Canada

Site Status

Princess Margaret Cancer Centre

Toronto, , Canada

Site Status

Vancouver General Hospital

Vancouver, , Canada

Site Status

Fakultni nemocnice Brno

Brno, , Czechia

Site Status

Fakultni nemocnice Hradec Kralove

Králová, , Czechia

Site Status

Fakutni nemocnice Ostrava

Ostrava, , Czechia

Site Status

Fakultni nemocnice Plzen

Pilsen, , Czechia

Site Status

CHRU de Lille - Hopital Claude Huriez

Lille, , France

Site Status

Hospices Civils De Lyon

Lyon, , France

Site Status

CHU De Nantes - Hématologie Clinique

Nantes, , France

Site Status

CHU Poitiers - Pôle régional de Cancérologie

Poitiers, , France

Site Status

Hopital Saint Louis - Aphp Hôpitaux Universitaires Saint-Louis

Saint-Louis, , France

Site Status

CHU de Toulouse

Toulouse, , France

Site Status

University Hospital of Cologne

Cologne, , Germany

Site Status

Universitätsklinikum Hamburg - Eppendorf

Hamburg, , Germany

Site Status

University Hospital of Leipzig

Leipzig, , Germany

Site Status

Tübingen

Tübingen, , Germany

Site Status

University Hospital of Würzburg

Würzburg, , Germany

Site Status

Attikon University General Hospital of Attica

Athens, , Greece

Site Status

'G. Papanikolaou' Hospital of Thessaloniki

Thessaloniki, , Greece

Site Status

Hadassah Medical Center

Jerusalem, , Israel

Site Status

Sheba medical center

Ramat Gan, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Kyushu University Hospital - Hematology/Oncology

Fukuoka, , Japan

Site Status

Hokkaido University Hospital-Department of Hematology

Hokkaido, , Japan

Site Status

Hyogo College of Medicine

Hyōgo, , Japan

Site Status

Kanazawa University Hospital

Kanazawa, , Japan

Site Status

Nagoya City University Hospital - Department of Hematology & Oncology

Nagoya, , Japan

Site Status

Okayama University Hospital - Hematology/Oncology

Okayama, , Japan

Site Status

Osaka metropolitan university hospital

Osaka, , Japan

Site Status

Japanese Red Cross Medical Center - Hematology

Shibuya City, , Japan

Site Status

Keio University Hospital - Hematology

Shinjuku-Ku, , Japan

Site Status

Tohoku University Hospital - Hematology

Tōhoku, , Japan

Site Status

VU Medisch Centrum

Amsterdam, , Netherlands

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Radboud UMC

Nijmegen, , Netherlands

Site Status

Erasmus MC

Rotterdam, , Netherlands

Site Status

UMC Utrecht

Utrecht, , Netherlands

Site Status

Oslo University Hospital Ullevål - Oncology

Oslo, , Norway

Site Status

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Spain

Site Status

Hospital Universitario Germans Trias i Pujol

Badalona, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Instituto Catalán de Oncología

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

CLINICA UNIV. DE NAVARRA, Pamplona

Pamplona, , Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital de Santiago de Compostela

Santiago de Compostela, , Spain

Site Status

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status

Hospital Universitario la Fe, Valencia

Valencia, , Spain

Site Status

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Site Status

Landstinget i Ostergotland-Universitetssjukhuset i Linkoping

Linköping, , Sweden

Site Status

Skånes University Hospital Lund

Lund, , Sweden

Site Status

Akademiska Sjukhuset

Uppsala, , Sweden

Site Status

Universitaetsspital Basel - Zentrum fur Hamato-Onkologie

Basel, , Switzerland

Site Status

Universitaetsspital Bern, Inselspital

Bern, , Switzerland

Site Status

Centre Hospitalier Universitaire Vaudois (CHUV)Département d'oncologie

Lausanne, , Switzerland

Site Status

Universitaetsspital Zuerich -Universitaeren Herzzentrum Zuerich

Zurich, , Switzerland

Site Status

Queen Elizabeth Medical Centre

Birmingham, , United Kingdom

Site Status

University Hospital of Wales

Cardiff, , United Kingdom

Site Status

Countries

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Italy South Korea United States Australia Belgium Canada Czechia France Germany Greece Israel Japan Netherlands Norway Spain Sweden Switzerland United Kingdom

Other Identifiers

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2021-003284-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMN28/68284528MMY3005

Identifier Type: -

Identifier Source: org_study_id