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

NCT05257083 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: EMN28/68284528MMY30052021-003284-10
• Study Type: interventional
• Target: 759
• Locations: 16 countries
• Sites: 106

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Progression free survival (PFS)

  Progression free survival is defined as the time from the date of randomization to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first

  up to 10 years ( or 300 PFS events)

• Sustained MRD-negative CR

  Sustained MRD-negative CR is defined as being MRD negative by bone marrow aspirate, as determined by NGS with a sensitivity of at least 10-5, and meeting the IMWG criteria for CR, and with MRD-negativity status confirmed at a minimum 12 months apart and without any examination showing MRD-positive status or PD in between.

  up to 24 months

Secondary Outcomes (11)

• Overall Response (OR)

  up to 17 years

• Complete Response (CR) or better status

  up to 17 years

• Overall Minimal Residual Disease (MRD) -negative CR

  up to 17 years

• Time to subsequent antimyeloma therapy

  up to 17 years

• Progression Free Survival on Next-line Therapy (PFS2)

  up to 17 years

Study Arms (2)

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

ACTIVE COMPARATOR

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

Drug: Daratumumab; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone

Arm B: DVRd followed by Ciltacabtagene Autoleucel

EXPERIMENTAL

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

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

Interventions

Daratumumab DRUG

Daratumumab will be administered SC.

Arm A: DVRd + ASCT+DVRd (Standard Therapy); Arm B: DVRd followed by Ciltacabtagene Autoleucel

Bortezomib DRUG

Bortezomib will be administered SC.

Arm A: DVRd + ASCT+DVRd (Standard Therapy); Arm B: DVRd followed by Ciltacabtagene Autoleucel

Lenalidomide DRUG

Lenalidomide will be administered orally.

Arm A: DVRd + ASCT+DVRd (Standard Therapy); Arm B: DVRd followed by Ciltacabtagene Autoleucel

Dexamethasone DRUG

Dexamethasone will be administered orally.

Arm A: DVRd + ASCT+DVRd (Standard Therapy); Arm B: DVRd followed by Ciltacabtagene Autoleucel

Cilta-cel DRUG

Cilta-cel will be administered intravenously

Also known as: JNJ-68284528

Arm B: DVRd followed by Ciltacabtagene Autoleucel

Cyclophosphamide DRUG

Cyclophosphamide will be administered intravenously.

Arm B: DVRd followed by Ciltacabtagene Autoleucel

Fludarabine DRUG

Fludarabine will be administered intravenously.

Arm B: DVRd followed by Ciltacabtagene Autoleucel

Eligibility Criteria

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

You may qualify if:

• 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:
• Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Stichting European Myeloma Network: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (106)

University of Arkansas

Little Rock, Arkansas, 72205, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

UC San Diego Health Moores Cancer Center

San Diego, California, 92093, United States

Location

University of California San Francisco (UCSF)

San Francisco, California, 94117, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Moffit Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University Of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Montefiore M-E Center

The Bronx, New York, 10467, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

University of Washington Medical

Seattle, Washington, 98195, United States

Location

Medical College Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Princess Alexandra Hospital

Brisbane, Australia

Location

Royal Prince Alfred Hospital

Camperdown, Australia

Location

Royal Brisbane and Womens Hospital

Herston, Australia

Location

Alfred Health

Melbourne, Australia

Location

Austin Hospital

Melbourne, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Australia

Location

Fiona Stanley Hospital

Murdoch, Australia

Location

Calvary Mater Newcastle Hospital

Waratah, Australia

Location

Westmead Hospital

Westmead, Australia

Location

Jules Bordet Instituut

Anderlecht, Belgium

Location

UZA

Antwerp, Belgium

Location

UZ Gent

Ghent, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

Cross Cancer Institute

Edmonton, Canada

Location

McMaster University

Hamilton, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Canada

Location

Mcgill University Health Centre

Montreal, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Canada

Location

(CHU) Centre Hospitalier Universitaire de Quebec Laval

Québec, Canada

Location

Princess Margaret Cancer Centre

Toronto, Canada

Location

Vancouver General Hospital

Vancouver, Canada

Location

Fakultni nemocnice Brno

Brno, Czechia

Location

Fakultni nemocnice Hradec Kralove

Králová, Czechia

Location

Fakutni nemocnice Ostrava

Ostrava, Czechia

Location

Fakultni nemocnice Plzen

Pilsen, Czechia

Location

CHRU de Lille - Hopital Claude Huriez

Lille, France

Location

Hospices Civils De Lyon

Lyon, France

Location

CHU De Nantes - Hématologie Clinique

Nantes, France

Location

CHU Poitiers - Pôle régional de Cancérologie

Poitiers, France

Location

Hopital Saint Louis - Aphp Hôpitaux Universitaires Saint-Louis

Saint-Louis, France

Location

CHU de Toulouse

Toulouse, France

Location

University Hospital of Cologne

Cologne, Germany

Location

Universitätsklinikum Hamburg - Eppendorf

Hamburg, Germany

Location

University Hospital of Leipzig

Leipzig, Germany

Location

Tübingen

Tübingen, Germany

Location

University Hospital of Würzburg

Würzburg, Germany

Location

Attikon University General Hospital of Attica

Athens, Greece

Location

'G. Papanikolaou' Hospital of Thessaloniki

Thessaloniki, Greece

Location

Hadassah Medical Center

Jerusalem, Israel

Location

Sheba medical center

Ramat Gan, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Juntendo University Hospital

Bunkyō City, Japan

Location

Kyushu University Hospital - Hematology/Oncology

Fukuoka, Japan

Location

Hokkaido University Hospital-Department of Hematology

Hokkaido, Japan

Location

Hyogo College of Medicine

Hyōgo, Japan

Location

Kanazawa University Hospital

Kanazawa, Japan

Location

Nagoya City University Hospital - Department of Hematology & Oncology

Nagoya, Japan

Location

Okayama University Hospital - Hematology/Oncology

Okayama, Japan

Location

Osaka metropolitan university hospital

Osaka, Japan

Location

Japanese Red Cross Medical Center - Hematology

Shibuya City, Japan

Location

Keio University Hospital - Hematology

Shinjuku-Ku, Japan

Location

Tohoku University Hospital - Hematology

Tōhoku, Japan

Location

VU Medisch Centrum

Amsterdam, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

Radboud UMC

Nijmegen, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

UMC Utrecht

Utrecht, Netherlands

Location

Oslo University Hospital Ullevål - Oncology

Oslo, Norway

Location

Hospital Universitario Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Instituto Catalán de Oncología

Barcelona, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

CLINICA UNIV. DE NAVARRA, Pamplona

Pamplona, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital de Santiago de Compostela

Santiago de Compostela, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

Hospital Universitario la Fe, Valencia

Valencia, Spain

Location

Sahlgrenska Universitetssjukhuset

Gothenburg, Sweden

Location

Landstinget i Ostergotland-Universitetssjukhuset i Linkoping

Linköping, Sweden

Location

Skånes University Hospital Lund

Lund, Sweden

Location

Akademiska Sjukhuset

Uppsala, Sweden

Location

Universitaetsspital Basel - Zentrum fur Hamato-Onkologie

Basel, Switzerland

Location

Universitaetsspital Bern, Inselspital

Bern, Switzerland

Location

Centre Hospitalier Universitaire Vaudois (CHUV)Département d'oncologie

Lausanne, Switzerland

Location

Universitaetsspital Zuerich -Universitaeren Herzzentrum Zuerich

Zurich, Switzerland

Location

Queen Elizabeth Medical Centre

Birmingham, United Kingdom

Location

University Hospital of Wales

Cardiff, United Kingdom

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Bortezomib; Lenalidomide; Dexamethasone; 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; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Design

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

Study Record Dates

• First Submitted: February 16, 2022
• First Posted: February 25, 2022
• Study Start: October 10, 2023
• Primary Completion (Estimated): June 1, 2033
• Study Completion (Estimated): August 1, 2040
• Last Updated: March 17, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (9); BE (4); GR (2); CH (4); SE (4); NO (1); NL (5); US (27); IL (3); ES (11); CA (8); FR (6); JP (11); GB (2); DE (5); CZ (4)