A Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Participants With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy
A Phase 3 Study Comparing Daratumumab, VELCADE (Bortezomib), Lenalidomide, and Dexamethasone (D-VRd) With VELCADE, Lenalidomide, and Dexamethasone (VRd) in Subjects With Untreated Multiple Myeloma and for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy
4 other identifiers
interventional
395
13 countries
114
Brief Summary
The purpose of this study to determine if the addition of daratumumab to bortezomib + lenalidomide + dexamethasone (VRd) will improve overall minimal residual disease (MRD) negativity rate compared with VRd alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 multiple-myeloma
Started Nov 2018
Typical duration for phase_3 multiple-myeloma
114 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 17, 2018
CompletedFirst Posted
Study publicly available on registry
August 29, 2018
CompletedStudy Start
First participant enrolled
November 6, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 7, 2024
CompletedResults Posted
Study results publicly available
April 8, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
April 21, 2026
CompletedJune 2, 2026
May 1, 2026
5.5 years
August 17, 2018
March 19, 2026
May 7, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Primary Analysis: Overall Minimal Residual Disease (MRD) Negative Rate
Overall MRD negativity rate was defined as the percentage of participants who achieved complete response (CR) or better response and had MRD negative status (at 10\^5) by bone marrow biopsy or aspirate after randomization but prior to progressive disease (PD), subsequent anti-myeloma therapy, or both. CR or better rate was defined as the percentage of participants achieving CR or stringent complete response (sCR) prior to subsequent anti-myeloma therapy in accordance with the International Myeloma Working Group (IMWG) criteria during or after the study treatment. CR was defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and less than (\<) 5 percent (%) plasma cells (PCs) in bone marrow. sCR was defined as CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.
From randomization (Day 1) up to 27.9 months
Final Progression-Free Survival (PFS) Analysis : Overall Minimal Residual Disease (MRD) Negative Rate
Overall MRD negativity rate was defined as the percentage of participants who achieved CR or better response and had MRD negative status (at 10\^5) by bone marrow biopsy or aspirate after randomization but prior to PD, subsequent anti-myeloma therapy, or both. CR or better rate was defined as the percentage of participants achieving CR or sCR prior to subsequent anti-myeloma therapy in accordance with the IMWG criteria during or after the study treatment. CR was defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and \< 5 % PCs in bone marrow. sCR was defined as CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.
From randomization (Day 1) up to 64.8 months
Secondary Outcomes (19)
Complete Response (CR) or Better Rate
From randomization (Day 1) up to 64.8 months
Progression-Free Survival (PFS)
From randomization (Day 1) up to 64.8 months
MRD Negativity Rate at 1 Year
At 1 Year
Overall Response Rate (ORR)
From randomization (Day 1) up to 64.8 months
Durable MRD Negative Rate
From randomization (Day 1) up to 64.8 months
- +14 more secondary outcomes
Study Arms (2)
Bortezomib + Lenalidomide + Dexamethasone (VRd) and Rd
ACTIVE COMPARATORParticipants will receive bortezomib 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection twice weekly on Days 1, 4, 8, 11 for Cycles 1 through 8 (each cycle is of 21 days); lenalidomide 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9 (cycle of 28 days); dexamethasone 20 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, 12 for Cycles 1 through 8 and 40 mg on Days 1,8, 15 and 22 during Cycle 9 and beyond (each cycle is of 28 days) followed by lenalidomide-dexamethasone (Rd) until disease progression or unacceptable toxicity. Participants aged greater than (\>)75 years or body mass index (BMI) less than (\<) 18.5 kilograms per meters (kg/m\^2) will receive dexamethasone 20 mg oral tablets on Days 1, 4, 8, and 11 of each cycle.
Daratumumab + VRd (D-VRd) and DRd
EXPERIMENTALParticipants will receive daratumumab 1800 mg as SC injection once every week for Cycles 1 to 2, then every 3 weeks for Cycles 3 through 8 and every 4 weeks for Cycle 9 and beyond; bortezomib 1.3 mg/m\^2 as SC injection twice weekly on Days 1, 4, 8, 11 for Cycles 1 through 8 (each cycle is of 21 days); lenalidomide 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9; dexamethasone 20 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, 12 for Cycles 1 through 8 and 40 mg on Days 1,8, 15 and 22 during Cycle 9 and beyond followed by daratumumab-lenalidomide-dexamethasone (DRd) until disease progression or unacceptable toxicity. Participants aged \>75 years or BMI \<18.5 kg/m\^2 will receive Dexamethasone 20 mg oral tablets on Days 1, 4, 8, and 11 of each cycle.
Interventions
Daratumumab (1800 mg) will be administered by SC injection once every week for Cycles 1 to 2, then every 3 weeks for Cycles 3-8. For Cycle 9 and beyond, participants will receive daratumumab 1800 mg SC once every 4 weeks until documented disease progression or unacceptable toxicity.
Bortezomib 1.3 mg/m\^2 will be administered by SC injection twice weekly on Days 1, 4, 8, and 11 of each 21-day cycle for Cycles 1-8.
Lenalidomide will be self-administered at a dose of 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9 and beyond until disease progression or unacceptable toxicity whichever occurs first.
Dexamethasone will be self-administered orally, 20 mg on Days 1, 2, 4, 5, 8, 9, 11, 12 of each 21-day cycle for Cycles 1-8. During Cycle 9 and beyond dexamethasone, will be self-administered orally at a total dose of 40 mg on Days 1, 8, 15, 22 of each 28-day cycle.
Eligibility Criteria
You may qualify if:
- \- Diagnosis of multiple myeloma as documented per International Myeloma Working Group (IMWG) criteria Monoclonal plasma cells in the bone marrow greater than or equal to (\>=)10 percentage (%) or presence of a biopsy proven plasmacytoma and documented multiple myeloma satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria. CRAB criteria: Hypercalcemia: serum calcium greater than (\>) 0.25 millimoles per liter (mmol/L) (\>1 milligram per deciliter \[mg/dL\]) higher than upper limit of normal (ULN) or \>2.75 mmol/L (\>11 mg/dL); Renal insufficiency: creatinine clearance less than (\<) 40 milliliter per minute (mL/min) or serum creatinine \>177 micro millimoles per liter (umol/L) (\>2 mg/dL); Anemia: hemoglobin \>2 g/dL below the lower limit of normal or hemoglobin \<10 g/dL; Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)-CT.
- Biomarkers of Malignancy: Clonal bone marrow plasma cell percentage \>=60%; Involved: uninvolved serum free light chain (FLC) ratio \>=100; \>1 focal lesion on magnetic resonance imaging (MRI) studies
- Must have measurable disease, as assessed by central laboratory
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 10 to 14 days prior to dosing and the second within 24 hours prior to dosing
- A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 3 months after receiving the last dose of any component of the treatment regimen
You may not qualify if:
- Frailty index of \>=2 according to Myeloma Geriatric Assessment score
- Prior therapy for multiple myeloma other than a short course of corticosteroids (not to exceed 40 mg of dexamethasone, or equivalent per day, total of 160 mg dexamethasone or equivalent)
- Prior or concurrent invasive malignancy (other than multiple myeloma) within 5 years of date of randomization (exceptions are adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)
- 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
- Focal radiation therapy within 14 days of randomization with the exception of palliative radiotherapy for symptomatic pain management. Radiotherapy within 14 days prior to randomization on measurable extramedullary plasmacytoma is not permitted even in the setting of palliation for symptomatic management
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (114)
Innovative Clinical Research Inc
Cerritos, California, 90703, United States
Baptist MD Anderson
Jacksonville, Florida, 32207, United States
Fort Wayne Medical Oncology and Hematology, Inc.
Fort Wayne, Indiana, 46804, United States
Norton Healthcare
Louisville, Kentucky, 40207, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Boston University Medical Center
Boston, Massachusetts, 02118, United States
Cancer And Hematology Centers of Western Michigan PC
Grand Rapids, Michigan, 49503, United States
Saint Lukes Hospital Saint Lukes Cancer Specialists
Kansas City, Missouri, 64111, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901, United States
San Juan Oncology Associates
Farmington, New Mexico, 87401, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
NYU Winthrop
Mineola, New York, 11501, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Good Samaritan Hospital Corvallis
Corvallis, Oregon, 97330, United States
University Of Pittsburgh Medical Center UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232 1301, United States
Gibbs Cancer Center
Spartanburg, South Carolina, 29303, United States
University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030, United States
University of Virginia
Charlottesville, Virginia, 22908, United States
Universidade Estadual De Campinas
Campinas, 13083-878, Brazil
Liga Norte Riograndense Contra O Cancer
Natal, 59062 000, Brazil
Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
Porto Alegre, 90610-000, Brazil
Ministerio da Saude Instituto Nacional do Cancer
Rio de Janeiro, 20230-130, Brazil
Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
Rio de Janeiro, 22775 001, Brazil
Instituto de Ensino e Pesquisa São Lucas
São Paulo, 01227-200, Brazil
Real e Benemerita Associacao Portuguesa de Beneficencia
São Paulo, 01323 900, Brazil
Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncologia
São Paulo, 03102-002, Brazil
Hospital Santa Cruz
São Paulo, 04122-000, Brazil
Clinica Medica Sao Germano S/S LTDA
São Paulo, 04537-081, Brazil
Arthur J E Child Comprehensive Cancer Centre
Calgary, Alberta, T2N 5G2, Canada
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
The Gordon & Leslie Diamond Health Care Center
Vancouver, British Columbia, V5Z 1M9, Canada
QEII Health Sciences Centre
Halifax, Nova Scotia, B3H 1V7, Canada
Brampton Civic Hospital
Brampton, Ontario, L6R 3J7, Canada
Victoria Hospital
London, Ontario, N6A 5W9, Canada
Lakeridge Health Oshawa
Oshawa, Ontario, L1G-2B9, Canada
McGill University Health Centre
Montreal, Quebec, H4A 3J1, Canada
CHU de Quebec L Hotel Dieu de Quebec
Québec, Quebec, G1J 1Z4, Canada
Fakultni nemocnice Brno
Brno, 625 00, Czechia
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05, Czechia
Fakultni Nemocnice Ostrava
Ostrava, 708 52, Czechia
Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
Pilsen, 323 00, Czechia
Vseobecna fakultni nemocnice v Praze
Prague, 128 08, Czechia
CHU Henri Mondor
Créteil, 94010, France
Centre Hospitalier Départmental La Roche sur Yon
La Roche-sur-Yon, 85925, France
Hopital Claude Huriez
Lille, 59037, France
Institut Paoli Calmettes
Marseille, 13009, France
CHU de Montpellier Hopital Saint Eloi
Montpellier, 34295, France
CHU de Bordeaux - Hospital Haut-Leveque
Pessac, 33604, France
Strasbourg Oncologie Libérale
Strasbourg, 67000, France
Institut Universitaire du cancer de Toulouse-Oncopole
Toulouse, 31059, France
phase 3 - Hämatoonkologischer Studienkreis am Klinikum Aschaffenburg
Aschaffenburg, 63739, Germany
Universitatsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
St. Josef-Krankenhaus Hamm-Bockum-Hövel
Hamm, 59075, Germany
Institut für Versorgungsforschung
Koblenz, 56068, Germany
Universitatsmedizin Leipzig
Leipzig, 4103, Germany
Klinikum Großhadern der Ludwig-Maximilians-Universität
München, 81377, Germany
Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,
Tübingen, 72076, Germany
Barzilai Medical Center
Ashkelon, 78741, Israel
Hillel Yaffe Medical Center
Hadera, 38100, Israel
Rambam Med.Center - Hematology Institute
Haifa, 3109601, Israel
Carmel Medical Center
Haifa, 3436212, Israel
Meir Hospital
Kfar Saba, 44281, Israel
Rabin Medical Center
Petah Tikva, 49100, Israel
Sheba Medical Center
Ramat Gan, 52621, Israel
Sourasky (Ichilov) Medical Center
Tel Aviv, 64239, Israel
Fukuoka University Hospital
Fukuoka, 814-0180, Japan
Ogaki Municipal Hospital
Gifu, 503-8502, Japan
Kanazawa University Hospital
Kanazawa, 920 8641, Japan
Kobe City Medical Center General Hospital
Kobe, 650 0047, Japan
National Hospital Organization Kumamoto Medical Center
Kumamoto, 860-0008, Japan
University Hospital Kyoto Prefectural University of Medicine
Kyoto, 602-8566, Japan
National Hospital Organization Matsumoto Medical Center
Matsumoto, 399-8701, Japan
Matsuyama Red Cross Hospital
Matsuyama, 790-8524, Japan
Nagoya City University Hospital
Nagoya, 467 8602, Japan
National Hospital Organization Okayama Medical Center
Okayama, 701-1192, Japan
Japanese Red Cross Osaka Hospital
Osaka, 543 8555, Japan
National Hospital Organization Shibukawa Medical Center
Shibukawa, 377-0280, Japan
Japanese Red Cross Medical Center
Shibuya City, 150-8935, Japan
VU Medisch Centrum
Amsterdam, 1081 HV, Netherlands
Albert Schweitzer ziekenhuis-lokatie Dordwijk
Dordrecht, 3318 AT, Netherlands
Erasmus MC
Rotterdam, 3015CE, Netherlands
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza
Brzozów, 36-200, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
Chorzów, 41-500, Poland
Uniwersyteckie Centrum Kliniczne
Gdansk, 80 214, Poland
Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
Kielce, 25 734, Poland
NSSU Szpital Uniwersytecki w Krakowie
Krakow, 30 688, Poland
Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli
Lublin, 20090, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
Poznan, 60-569, Poland
Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka
Słupsk, 76-200, Poland
Instytut Hematologii i Transfuzjologii
Warsaw, 02 776, Poland
Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
Warsaw, 02-781, Poland
Hosp. Univ. Fundacion Alcorcon
Alcorcón, 28922, Spain
Hosp. Del Mar
Barcelona, 08003, Spain
Hosp. Univ. de Guadalajara
Guadalajara, 19002, Spain
Hosp. Univ. Pta. de Hierro Majadahonda
Majadahonda, 28222, Spain
Hosp. Quiron Madrid Pozuelo
Pozuelo de Alarcón, 28223, Spain
Hosp. Mutua Terrassa
Terrassa, 08221, Spain
Gulhane Egitim ve Arastirma Hastanesi
Ankara, 06010, Turkey (Türkiye)
Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital
Ankara, 06200, Turkey (Türkiye)
Hacettepe Universitesi Tip Fakultesi
Ankara, 06230, Turkey (Türkiye)
Ankara University School of Medicine Cebeci Hospital
Ankara, 06590, Turkey (Türkiye)
Istanbul University Istanbul Medical Faculty
Istanbul, 34093, Turkey (Türkiye)
Dokuz Eylul University Medical Faculty
Izmir, 35340, Turkey (Türkiye)
On Dokuz Mayis Universitesi Tip Fakultesi
Samsun, 55200, Turkey (Türkiye)
Monklands District General Hospital
Airdrie, ML6 0JS, United Kingdom
Blackpool Victoria Hospital
Blackpool, FY3 8NR, United Kingdom
University Hospital Wales
Cardiff, CF14 4XN, United Kingdom
Colchester Hospital University NHS
Colchester, CO4 5JL, United Kingdom
Leicester Royal Infirmary - Haematology
Leicester, LE1 5WW, United Kingdom
Altnagelvin Hospital
Londonderry, BT47 6SB, United Kingdom
The Royal Oldham Hospital
Oldham, OL1 2JH, United Kingdom
Derriford Hospital
Plymouth, PL6 8DH, United Kingdom
New Cross Hospital
Wolverhampton, WV10 0QP, United Kingdom
Related Publications (2)
Usmani SZ, Facon T, Hungria V, Bahlis NJ, Venner CP, Braunstein M, Pour L, Marti JM, Basu S, Cohen YC, Matsumoto M, Suzuki K, Hulin C, Grosicki S, Legiec W, Beksac M, Maiolino A, Takamatsu H, Perrot A, Turgut M, Ahmadi T, Liu W, Wang J, Chastain K, Vermeulen J, Krevvata M, Lopez-Masi L, Carey J, Rowe M, Carson R, Zweegman S. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial. Nat Med. 2025 Apr;31(4):1195-1202. doi: 10.1038/s41591-024-03485-7. Epub 2025 Feb 5.
PMID: 39910273DERIVEDAbdallah N, Kumar SK. Up-Front Treatment of Elderly (Age >/=75 Years) and Frail Patients With Multiple Myeloma. J Natl Compr Canc Netw. 2024 Nov;22(9):e247039. doi: 10.6004/jnccn.2024.7039.
PMID: 39536451DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Janssen Research & Development, LLC
Study Officials
- STUDY DIRECTOR
Janssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 17, 2018
First Posted
August 29, 2018
Study Start
November 6, 2018
Primary Completion
May 7, 2024
Study Completion
April 21, 2026
Last Updated
June 2, 2026
Results First Posted
April 8, 2026
Record last verified: 2026-05