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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Daratumumab

Detailed Description

This study will evaluate participants with newly diagnosed multiple myeloma (MM) for whom hematopoietic stem cell transplant is not planned as initial therapy. The data available from other available studies suggests that addition of daratumumab with Velcade (bortezomib), lenalidomide, and dexamethasone [VRd] is anticipated to improve the response rates and the depth of response and may lead to improved long-term outcomes in newly diagnosed participants with MM. Daratumumab targets CD38, a protein expressed on the surface of MM cells and other hematopoietic cells. Bortezomib is a proteasome inhibitor, which plays a critical role in the pathogenesis of MM. Lenalidomide has cytotoxic effects on myeloma cells and is capable of inducing apoptosis, or programmed cell death and dexamethasone induces apoptosis in MM cells. The rationale for the study is to utilize the subcutaneous (SC) formulation of daratumumab instead of the intravenous (IV) formulation, which is expected to provide similar exposure and is expected to limit additional toxicity to participants, treated with this quadruplet regimen. The study will consist of 3 phases: Screening (up to 28 days before randomization), Treatment phase (from Cycle 1 [21 days] Day 1 and continues until disease progression) and Follow up (Postintervention). Efficacy evaluations will include measurements of tumor burden/residual disease, myeloma proteins, bone marrow examinations, skeletal surveys, extramedullary plasmacytomas, and serum calcium corrected for albumin. Participants will undergo procedures like electrocardiogram (ECG), chest x-rays or full dose chest CT scans, Pulmonary function test (PFT), spirometry etc. during the course of study. Participants will also be monitored closely for adverse events (AEs), laboratory abnormalities, and clinical response. The duration of the study will be approximately 6.5 years.

• Study Type: Interventional
• Enrollment (Actual): 395
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Campinas, Brazil, 13083-878
    • Universidade Estadual De Campinas
  • Natal, Brazil, 59062 000
    • Liga Norte Riograndense Contra o Câncer
  • Porto Alegre, Brazil, 90610-000
    • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
  • Rio de Janeiro, Brazil, 20230-130
    • Ministerio da Saude Instituto Nacional do Cancer
  • Rio de Janeiro, Brazil, 22775 001
    • Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
  • São Paulo, Brazil, 04122-000
    • Hospital Santa Cruz
  • São Paulo, Brazil, 01323 900
    • Real e Benemerita Associacao Portuguesa de Beneficencia
  • São Paulo, Brazil, 01227-200
    • Instituto de Ensino e Pesquisa São Lucas
  • São Paulo, Brazil, 03102-002
    • Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncologia
  • São Paulo, Brazil, 04537-081
    • Clínica Médica São Germano S/S Ltda
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J E Child Comprehensive Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • The Gordon & Leslie Diamond Health Care Center
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Centre
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Brampton Civic Hospital
    • London, Ontario, Canada, N6A 5W9
      • Victoria Hospital
    • Oshawa, Ontario, Canada, L1G-2B9
      • Lakeridge Health Oshawa
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
    • Québec, Quebec, Canada, G1J 1Z4
      • CHU de Quebec L Hotel Dieu de Quebec
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni Nemocnice Brno
  • Hradec Králové, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Ostrava, Czechia, 708 52
    • Fakultní nemocnice Ostrava
  • Pilsen, Czechia, 323 00
    • Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
  • Prague, Czechia, 128 08
    • Vseobecna Fakultni nemocnice v Praze
• France
  • Créteil, France, 94010
    • CHU Henri Mondor
  • La Roche-sur-Yon, France, 85925
    • Centre Hospitalier Départmental La Roche sur Yon
  • Lille, France, 59037
    • Hopital Claude Huriez
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Montpellier, France, 34295
    • CHU de Montpellier Hopital Saint Eloi
  • Pessac, France, 33604
    • CHU de Bordeaux - Hospital Haut-Leveque
  • Strasbourg, France, 67000
    • Strasbourg Oncologie Libérale
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer de Toulouse-Oncopole
• Germany
  • Aschaffenburg, Germany, 63739
    • phase 3 - Hämatoonkologischer Studienkreis am Klinikum Aschaffenburg
  • Freiburg im Breisgau, Germany, 79106
    • Universitätsklinikum Freiburg
  • Hamm, Germany, 59075
    • St. Josef-Krankenhaus Hamm-Bockum-Hövel
  • Koblenz, Germany, 56068
    • Institut für Versorgungsforschung
  • Leipzig, Germany, 4103
    • Universitatsmedizin Leipzig
  • München, Germany, 81377
    • Klinikum Grosshadern Der Ludwig-Maximilians-Universitat
  • Tübingen, Germany, 72076
    • Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,
• Israel
  • Ashkelon, Israel, 78741
    • Barzilai Medical Center
  • Hadera, Israel, 38100
    • Hillel Yaffe Medical Center
  • Haifa, Israel, 3436212
    • Carmel Medical Center
  • Haifa, Israel, 3109601
    • Rambam Med.Center - Hematology Institute
  • Kfar Saba, Israel, 44281
    • Meir Hospital
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Sourasky (Ichilov) Medical Center
• Japan
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Gifu, Japan, 503-8502
    • Ogaki Municipal Hospital
  • Kanazawa, Japan, 920 8641
    • Kanazawa University Hospital
  • Kobe, Japan, 650 0047
    • Kobe City Medical Center General Hospital
  • Kumamoto, Japan, 860-0008
    • National Hospital Organization Kumamoto Medical Center
  • Kyoto, Japan, 602-8566
    • University Hospital Kyoto Prefectural University of Medicine
  • Matsumoto, Japan, 399-8701
    • National Hospital Organization Matsumoto Medical Center
  • Matsuyama, Japan, 790-8524
    • Matsuyama Red Cross Hospital
  • Nagoya, Japan, 467 8602
    • Nagoya City University Hospital
  • Okayama, Japan, 701-1192
    • National Hospital Organization Okayama Medical Center
  • Osaka, Japan, 543 8555
    • Japanese Red Cross Osaka Hospital
  • Shibukawa, Japan, 377-0280
    • National Hospital Organization Shibukawa Medical Center
  • Shibuya City, Japan, 150-8935
    • Japanese Red Cross Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum
  • Dordrecht, Netherlands, 3318 AT
    • Albert Schweitzer ziekenhuis-lokatie Dordwijk
  • Rotterdam, Netherlands, 3015CE
    • Erasmus MC
• Poland
  • Brzozów, Poland, 36-200
    • Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza
  • Chorzów, Poland, 41-500
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
  • Gdansk, Poland, 80 214
    • Uniwersyteckie Centrum Kliniczne
  • Kielce, Poland, 25 734
    • Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
  • Krakow, Poland, 30 688
    • NSSU Szpital Uniwersytecki w Krakowie
  • Lublin, Poland, 20090
    • Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli
  • Poznan, Poland, 60-569
    • Uniwersytecki Szpital Kliniczny W Poznaniu
  • Słupsk, Poland, 76-200
    • Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka
  • Warsaw, Poland, 02-781
    • Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
  • Warsaw, Poland, 02 776
    • Instytut Hematologii i Transfuzjologii
• Spain
  • Alcorcón, Spain, 28922
    • Hosp. Univ. Fundacion Alcorcon
  • Barcelona, Spain, 08003
    • Hosp. Del Mar
  • Guadalajara, Spain, 19002
    • Hosp. Univ. de Guadalajara
  • Majadahonda, Spain, 28222
    • Hosp. Univ. Pta. de Hierro Majadahonda
  • Pozuelo de Alarcón, Spain, 28223
    • Hosp. Quiron Madrid Pozuelo
  • Terrassa, Spain, 08221
    • Hosp. Mutua Terrassa
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06200
    • Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital
  • Ankara, Turkey (Türkiye), 06010
    • Gulhane Egitim ve Arastirma Hastanesi
  • Ankara, Turkey (Türkiye), 06590
    • Ankara University School of Medicine Cebeci Hospital
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Universitesi Tip Fakultesi
  • Istanbul, Turkey (Türkiye), 34093
    • Istanbul University Istanbul Medical Faculty
  • Izmir, Turkey (Türkiye), 35340
    • Dokuz Eylul University Medical Faculty
  • Samsun, Turkey (Türkiye), 55200
    • On Dokuz Mayis Universitesi Tip Fakultesi
• United Kingdom
  • Airdrie, United Kingdom, ML6 0JS
    • Monklands District General Hospital
  • Blackpool, United Kingdom, FY3 8NR
    • Blackpool Victoria Hospital
  • Cardiff, United Kingdom, CF14 4XN
    • University Hospital Wales
  • Colchester, United Kingdom, CO4 5JL
    • Colchester Hospital University NHS
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary - Haematology
  • Londonderry, United Kingdom, BT47 6SB
    • Altnagelvin Hospital
  • Oldham, United Kingdom, OL1 2JH
    • The Royal Oldham Hospital
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital
• United States
  • California
    • Cerritos, California, United States, 90703
      • Innovative Clinical Research Inc
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology, Inc.
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Healthcare
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Cancer And Hematology Centers of Western Michigan PC
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Lukes Hospital Saint Lukes Cancer Specialists
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • New Mexico
    • Farmington, New Mexico, United States, 87401
      • San Juan Oncology Associates
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Mineola, New York, United States, 11501
      • NYU Winthrop
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • Good Samaritan Hospital Corvallis
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232 1301
      • University Of Pittsburgh Medical Center UPMC Hillman Cancer Center
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas, MD Anderson Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bortezomib + Lenalidomide + Dexamethasone (VRd) and Rd; Participants 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.	Drug: Bortezomib; 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.; Other Names: Velcade; Drug: Lenalidomide; 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.; Other Names: Revlimid; Drug: Dexamethasone; 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.
Experimental: Daratumumab + VRd (D-VRd) and DRd; Participants 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.	Drug: Bortezomib; 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.; Other Names: Velcade; Drug: Lenalidomide; 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.; Other Names: Revlimid; Drug: Dexamethasone; 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.; Drug: Daratumumab; 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.; Other Names: JNJ-54767414; DARZALEX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Very Good Partial Response (VGPR) or Better Rate	From randomization (Day 1) up to 64.8 months
Duration of Response (DOR)	From randomization (Day 1) up to 64.8 months
Time to Response	From randomization (Day 1) up to 64.8 months
PFS on the Next Line of Therapy	From randomization (Day 1) up to 64.8 months
Overall Survival (OS)	From screening (-28 Days) up to 64.8 months
Overall MRD Negativity Rate in High-risk Molecular Subgroups	From randomization (Day 1) up to 64.8 months
PFS in High-risk Molecular Subgroups	From randomization (Day 1) up to 64.8 months
Maximum Observed Serum Concentration (Cmax) of Daratumumab	Predose on Day 1 and post dose on Day 4 of Cycles 1, 3 (each cycle consisted of 21 days); Predose on Day 1 of Cycles 9 and 12 (each cycle consisted of 28 days); Post treatment Week 8
Minimum Observed Serum Concentration (Cmin) of Daratumumab	Predose on Day 1 and post dose on Day 4 of Cycles 1 and 3 (each cycle consisted of 21 days); Predose on Day 1 of Cycles 9 and 12 (each cycle consisted of 28 days); Post treatment Week 8
Number of Participants With Anti-daratumumab Antibodies	Predose on Day 1 of Cycles 1, 9, and 12 (Cycle 1 consisted of 21 days, Cycles 9 and 12 consisted of 28 days); and Post-Treatment Week 8
Number of Participants With Anti-recombinant Human Hyaluronidase PH20 (Anti-rHuPH20) Antibodies	Predose on Day 1 of Cycles 1, 9, and 12 (Cycle 1 consisted of 21 days, Cycles 9 and 12 consisted of 28 days); and Post-Treatment Week 8
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Item (EORTC QLQ-C30)	From screening (-28 Days) up to 64.8 months
Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma 20-item (EORTC QLQ-MY20)	From screening (-28 Days) up to 64.8 months
Mean Change From Baseline in EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L)	From screening (-28 Days) up to 64.8 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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.
• Abdallah 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2018
• Primary Completion (Actual): May 7, 2024
• Study Completion (Actual): April 21, 2026

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: August 28, 2018
• First Posted (Actual): August 29, 2018

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Polycyclic Compounds; Piperidines; Inorganic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Bortezomib; Dexamethasone; daratumumab
• Other Study ID Numbers: CR108529; 2018-001545-13 (EudraCT Number); 54767414MMY3019 (Other Identifier: Janssen Research & Development, LLC); 2023-507312-13-00 (Registry Identifier: EUCT number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No