A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma

NCT ID: NCT04181827

Last Updated: 2025-11-13

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

419 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-12

Study Completion Date

2029-04-09

Brief Summary

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The purpose of this study is to compare the efficacy of ciltacabtagene autoleucel (cilta-cel) with standard therapy, either Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd).

Detailed Description

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Conditions

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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: PVd or DPd (Standard Therapy)

Participants will receive either PVd or DPd as a standard therapy. In PVd treatment, participants will receive oral pomalidomide 4 mg on Days 1 to 14 in each cycle; bortezomib 1.3 mg/meter square (m\^2) SC on Days 1, 4, 8 and 11 (Cycles 1 to 8) and on Days 1 and 8 (Cycle 9 onwards) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 (Cycles 1 to 8) and Days 1, 2, 8 and 9 (Cycle 9 onwards). Each cycle will consist of 21 days. In DPd treatment, participants will receive daratumumab SC 1800 mg weekly on Days 1, 8, 15, and 22 (Cycles 1 and 2), every 2 weeks on Days 1 and 15 (Cycles 3 to 6) and every 4 weeks on Day 1 (Cycle 7 onwards); oral pomalidomide 4 mg on Days 1 to 21 (Cycle 1 onwards); dexamethasone 40 mg oral or IV weekly on Days 1, 8, 15, and 22 (Cycle 1 onwards). Each cycle will consist of 28 days. Participants will continue to receive PVd or DPd until confirmed PD, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs earlier.

Group Type EXPERIMENTAL

Pomalidomide

Intervention Type DRUG

Pomalidomide 4 mg will be administered orally.

Bortezomib

Intervention Type DRUG

Bortezomib 1.3 milligram per meter square (mg/m\^2) will be administered subcutaneously (SC).

Dexamethasone

Intervention Type DRUG

Dexamethasone 20 mg/day (10mg/day for participants \>75 years of age) (on bortezomib treatment days and the days following bortezomib treatment) will be administered orally in PVd treatment; and orally or intravenous (IV) at 40 mg weekly (20mg weekly for participants \>75 years of age) in DPd treatment.

Daratumumab

Intervention Type DRUG

Daratumumab 1800 mg will be administered SC.

Arm B: (Ciltacabtagene Autoleucel [Cilta-cel])

Participants will receive at least one cycle of bridging therapy (PVd or DPd) and additional cycles of bridging therapy may be considered based on participant's clinical status and timing of availability of cilta-cel along with conditioning regimen (cyclophosphamide 300 milligram \[mg\]/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

Cilta-cel

Intervention Type DRUG

Cilta-cel infusion will be administered at a target dose of 0.75 \* 10\^6 CAR-positive viable T cells/kilogram (kg).

Interventions

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Cilta-cel

Cilta-cel infusion will be administered at a target dose of 0.75 \* 10\^6 CAR-positive viable T cells/kilogram (kg).

Intervention Type DRUG

Pomalidomide

Pomalidomide 4 mg will be administered orally.

Intervention Type DRUG

Bortezomib

Bortezomib 1.3 milligram per meter square (mg/m\^2) will be administered subcutaneously (SC).

Intervention Type DRUG

Dexamethasone

Dexamethasone 20 mg/day (10mg/day for participants \>75 years of age) (on bortezomib treatment days and the days following bortezomib treatment) will be administered orally in PVd treatment; and orally or intravenous (IV) at 40 mg weekly (20mg weekly for participants \>75 years of age) in DPd treatment.

Intervention Type DRUG

Daratumumab

Daratumumab 1800 mg will be administered SC.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Measurable disease at screening as defined by any of the following: (a) Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=) 0.5 gram per deciliter (g/dL) or urine M-protein level \>=200 milligram (mg)/24 hours; or (b) Light chain multiple myeloma without measurable M-protein in the serum or the urine: Serum free light chain \>=10 mg/dL and abnormal serum free light chain ratio
* Have received 1 to 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
* Have documented evidence of PD by International Myeloma Working Group (IMWG) criteria based on investigator's determination on or within 6 months of their last regimen
* Be refractory to lenalidomide per IMWG consensus guidelines (failure to achieve minimal response or progression on or within 60 days of completing lenalidomide therapy). Progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion. For participants with more than 1 prior line of therapy, there is no requirement to be lenalidomide refractory to the most recent line of prior therapy. However, participants must be refractory to lenalidomide in at least one prior line
* Have clinical laboratory values meeting the following criteria during the Screening Phase (re testing is allowed but the below criteria must be met in the latest test prior to randomization):

1. Hemoglobin \>=8 gram per deciliter (g/dL) (without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted);
2. Absolute neutrophil count (ANC) \>=1 \* 10\^9 per liter (L) (without recombinant human granulocyte colony-stimulating factor \[G-CSF\] within 7 days and without pegylated G-CSF within 14 days of the laboratory test);
3. Platelet count \>=75 \* 10\^9/L (without prior platelet transfusion within 7 days before the laboratory test) in participants in whom less than (\<) 50 percent (%) of bone marrow nucleated cells are plasma cells; platelet count \>=50 \* 10\^9/L (without prior platelet transfusion within 7 days before the laboratory test) in participants in whom \>=50% of bone marrow nucleated cells are plasma cells;
4. Lymphocyte count \>=0.3 \* 10\^9/L;
5. Aspartate aminotransferase (AST) less than or equal to (\<=)3 \* upper limit of normal (ULN);
6. Alanine aminotransferase (ALT) \<=3 \* ULN;
7. Total bilirubin \<=2.0 \* ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin \<=1.5 \* ULN is required);
8. Estimated glomerular filtration rate \>=40 milliliter per minute (mL/min) per 1.73 meter square (m\^2) (to be calculated using the Modification of Diet in Renal Disease \[MDRD\] formula)

Exclusion Criteria

* Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy directed at any target
* Any previous therapy that is targeted to B-cell maturation antigen (BCMA)
* Ongoing toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade 1 or less; except for alopecia
* Participants with Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy will not be permitted to receive pomalidomide, bortezomib, and dexamethasone (PVd) as standard therapy or bridging therapy; however, participants may receive daratumumab, pomalidomide, and dexamethasone (DPd) as standard therapy or bridging therapy
* Received a cumulative dose of corticosteroids equivalent to \>=70 mg of prednisone within the 7 days prior to randomization
* Monoclonal antibody treatment within 21 days
* Cytotoxic therapy within 14 days
* Proteasome inhibitor therapy within 14 days
* Immunomodulatory drug (IMiD) therapy within 7 days
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Mayo Clinic Cancer Center-Scottsdale

Phoenix, Arizona, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

University Of Miami Leonard M Mille School Of Medicine SCCC

Miami, Florida, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas

Westwood, Kansas, United States

Site Status

University Of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status

Washington University School Of Medicine

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Wisconsin Institutes for Medical Research

Madison, Wisconsin, United States

Site Status

Medical College Of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Royal Adelaide Hospital

Adelaide, , Australia

Site Status

Royal Prince Alfred Hospital

Camperdown, , Australia

Site Status

Royal Brisbane and Womens Hospital

Herston, , Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, , Australia

Site Status

Alfred Health

Melbourne, , Australia

Site Status

Fiona Stanley Hospital

Murdoch, , Australia

Site Status

Universitair Ziekenhuis - Antwerpen

Antwerp, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman

Liège, , Belgium

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

CHRU de Lille Hopital Claude Huriez

Lille, , France

Site Status

CHU de Montpellier Hopital Saint Eloi

Montpellier, , France

Site Status

C.H.U. Hotel Dieu - France

Nantes, , France

Site Status

Hopital Saint Louis

Paris, , France

Site Status

Centre hospitalier Lyon-Sud

Pierre-Bénite, , France

Site Status

CHU De Poitiers

Poitiers, , France

Site Status

Institut Universitaire du cancer de Toulouse-Oncopole

Toulouse, , France

Site Status

Universitaetsklinikum Koeln

Cologne, , Germany

Site Status

Universitatsklinikum Carl Gustvav Carus Dresden an der Technischen Universitat Dresden

Dresden, , Germany

Site Status

Universitaetsklinikum Hamburg Eppendorf

Hamburg, , Germany

Site Status

Universitaetsklinikum Leipzig

Leipzig, , Germany

Site Status

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

Tübingen, , Germany

Site Status

Universitatsklinikum Wurzburg

Würzburg, , Germany

Site Status

Attikon University General Hospital of Attica

Athens, , Greece

Site Status

Hadassah University Hospita Ein Kerem

Jerusalem, , Israel

Site Status

Sheba Medical Center

Ramat Gan, , Israel

Site Status

Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna

Bologna, , Italy

Site Status

IRCCS Ospedale San Raffaele HSR

Milan, , Italy

Site Status

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status

Policlinico Universitario Agostino Gemelli

Roma, , Italy

Site Status

A.O.U. Citta della Salute e della Scienza di Torino - Presidio Molinette

Turin, , Italy

Site Status

Kyushu University Hospital

Fukuoka, , Japan

Site Status

Kanazawa University Hospital

Kanazawa, , Japan

Site Status

University Hospital Kyoto Prefectural University of Medicine

Kyoto, , Japan

Site Status

Nagoya City University Hospital

Nagoya, , Japan

Site Status

Okayama University Hospital

Okayama, , Japan

Site Status

Hokkaido University Hospital

Sapporo, , Japan

Site Status

Tohoku University Hospital

Sendai, , Japan

Site Status

Japanese Red Cross Medical Center

Shibuya City, , Japan

Site Status

VU Medisch Centrum

Amsterdam, , Netherlands

Site Status

University Medical Center Groningen

Groningen, , Netherlands

Site Status

Erasmus MC

Rotterdam, , Netherlands

Site Status

UMC Utrecht

Utrecht, , Netherlands

Site Status

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Site Status

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

Gliwice, , Poland

Site Status

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, , Poland

Site Status

Instytut Hematologii i Transfuzjologii

Warsaw, , Poland

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

The Catholic University of Korea Seoul St Marys Hospital

Seoul, , South Korea

Site Status

Inst. Cat. D'Oncologia-Badalona

Badalona, , Spain

Site Status

Hosp Clinic de Barcelona

Barcelona, , Spain

Site Status

Hosp. Gral. Univ. Gregorio Maranon

Madrid, , Spain

Site Status

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Site Status

Clinica Univ. de Navarra

Pamplona, , Spain

Site Status

Hosp Clinico Univ de Salamanca

Salamanca, , Spain

Site Status

Hosp. Virgen Del Rocio

Seville, , Spain

Site Status

Skane University Hospital

Lund, , Sweden

Site Status

Karolinska Universitetssjukhuset Huddinge, Hematologiska Kliniken, Huddinge

Stockholm, , Sweden

Site Status

Akademiska Sjukhuset

Uppsala, , Sweden

Site Status

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status

Bristol Haematology and Oncology Centre

Bristol, , United Kingdom

Site Status

University Hospital Wales

Cardiff, , United Kingdom

Site Status

University College Hospital

London, , United Kingdom

Site Status

Kings College Hospital

London, , United Kingdom

Site Status

Christie Hospital

Manchester, , United Kingdom

Site Status

Freeman Hospital

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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Austria United States Australia Belgium Denmark France Germany Greece Israel Italy Japan Netherlands Poland South Korea Spain Sweden United Kingdom

References

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Touzeau C, Lipe B, Khan AM, Dhakal B, Nair S, He J, Mendes J, Lee S, Lonardi C, Slaughter A, Lendvai N, Schecter JM, Chen D, Zhao M, Yeh TM, Leleu X, Puig N, Dytfeld D, Zamagni E, Weisel K, Karlin L, Delforge M, Corradini P, Mina R, Roeloffzen W, Sidana S. Comparative Effectiveness of Ciltacabtagene Autoleucel in CARTITUDE-4 Versus Real-World Physician's Choice of Therapy from the Flatiron Registry in Lenalidomide-Refractory Multiple Myeloma. Adv Ther. 2025 Oct;42(10):5023-5041. doi: 10.1007/s12325-025-03308-2. Epub 2025 Aug 6.

Reference Type DERIVED
PMID: 40768190 (View on PubMed)

Fonseca R, Diels J, Ghilotti F, Mendes J, Van Hoorenbeeck S, Lee S, Schecter JM, Lendvai N, Patel N, Triguero A, Alsdorf W, van de Donk NWCJ, Ursi M. Survival Outcomes with Cilta-cel Versus Conventional Treatment Regimens for Patients with Lenalidomide-Refractory Multiple Myeloma Using Inverse Probability of Treatment Weighting. Adv Ther. 2025 Sep;42(9):4418-4431. doi: 10.1007/s12325-025-03278-5. Epub 2025 Jul 4.

Reference Type DERIVED
PMID: 40613875 (View on PubMed)

Harrison SJ, Touzeau C, Kint N, Li K, Nguyen T, Mayeur-Rousse C, Rahman M, Le Bris Y, Er J, Eugene-Lamer J, Haynes NM, Li J, Abbott RC, Bodet-Milin C, Moreau A, Letouze E, Lendvai N, Schecter JM, Deraedt W, Banerjee A, Lengil T, Vogel M, Foulk B, Zhao H, Smirnov D, Slaughter A, Lonardi C, Lee E, Marquez L, Sankari A, Plaks V, Filho JOC, Patel N, Geng D, Gastinne T, Kelly H, Tiong IS, Eveillard M, Chevallier P, Lade S, Moreau P, Grimmond S, Oliaro J, Tessoulin B, Blombery P. CAR+ T-Cell Lymphoma after Cilta-cel Therapy for Relapsed or Refractory Myeloma. N Engl J Med. 2025 Feb 13;392(7):677-685. doi: 10.1056/NEJMoa2309728.

Reference Type DERIVED
PMID: 39938094 (View on PubMed)

Mina R, Mylin AK, Yokoyama H, Magen H, Alsdorf W, Minnema MC, Shune L, Isufi I, Harrison SJ, Shah UA, Schecter JM, Vogel M, Lendvai N, Gries KS, Katz EG, Slaughter A, Lonardi C, Gilbert J, Li Q, Deraedt W, Filho OC, Patel N, Florendo E, Karlin L, Weisel K. Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial. Lancet Haematol. 2025 Jan;12(1):e45-e56. doi: 10.1016/S2352-3026(24)00320-X.

Reference Type DERIVED
PMID: 39756844 (View on PubMed)

San-Miguel J, Dhakal B, Patel N, Schecter JM, Lendvai N, Einsele H. Plain language summary of the CARTITUDE-4 study of ciltacabtagene autoleucel for the treatment of people with relapsed or refractory multiple myeloma. Future Oncol. 2024;20(33):2509-2520. doi: 10.1080/14796694.2024.2376973. Epub 2024 Aug 7.

Reference Type DERIVED
PMID: 39110421 (View on PubMed)

San-Miguel J, Dhakal B, Yong K, Spencer A, Anguille S, Mateos MV, Fernandez de Larrea C, Martinez-Lopez J, Moreau P, Touzeau C, Leleu X, Avivi I, Cavo M, Ishida T, Kim SJ, Roeloffzen W, van de Donk NWCJ, Dytfeld D, Sidana S, Costa LJ, Oriol A, Popat R, Khan AM, Cohen YC, Ho PJ, Griffin J, Lendvai N, Lonardi C, Slaughter A, Schecter JM, Jackson CC, Connors K, Li K, Zudaire E, Chen D, Gilbert J, Yeh TM, Nagle S, Florendo E, Pacaud L, Patel N, Harrison SJ, Einsele H. Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. N Engl J Med. 2023 Jul 27;389(4):335-347. doi: 10.1056/NEJMoa2303379. Epub 2023 Jun 5.

Reference Type DERIVED
PMID: 37272512 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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68284528MMY3002

Identifier Type: OTHER

Identifier Source: secondary_id

2019-001413-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506588-32-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR108695

Identifier Type: -

Identifier Source: org_study_id