A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma

Smoldering Multiple Myeloma Clinical Trial

Official title:

A Phase 3 Randomized, Multicenter Study of Subcutaneous Daratumumab Versus Active Monitoring in Subjects With High-Risk Smoldering Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03301220
• Other study ID #: CR108172
• Secondary ID: 54767414SMM30012
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 7, 2017
• Est. completion date: July 11, 2025

Study information

• Verified date: April 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine whether treatment with daratumumab administered subcutaneously (SC) prolongs progression-free survival (PFS) compared with active monitoring in participants with high-risk smoldering multiple myeloma (SMM).

Description:

This study consists of 3 phases: Screening Phase (up to 35 days), an Active Monitoring Phase or a Treatment Phase of 39 cycles or 36 months (whichever occurs first), and a Follow-up Phase which will continue until death, lost to follow-up, consent withdrawal, or study end (approximately 8 years after the first participant is randomized), whichever occurs first. Active monitoring cycles and treatment cycles are 4 weeks in length. For all participants, disease evaluations will be performed every 12 weeks until confirmed progressive disease (PD). After PD, survival is to be followed at least every 6 months, until the end of the study. Participants will undergo tumor assessments, pharmacokinetics, biomarkers and safety evaluations (adverse events, laboratory tests, vital sign measurements, physical examinations, Eastern Cooperative Oncology Group [ECOG] performance status) over the time.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 390
• Est. completion date: July 11, 2025
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of high risk smoldering multiple myeloma (SMM) (per International Myeloma Working Group [IMWG] criteria) for less than or equal to (<=) 5 years with measurable disease at the time of randomization, defined as serum M protein greater than or equal to (>=) 10 gram per liter (g/L) or urine M protein >= 200 milligram per 24 hours (mg/24 hours) or involved serum free light chain (FLC) >=100 milligram per liter (mg/L) and abnormal serum FLC ratio
• Clonal bone marrow plasma cells (BMPCs) >= 10 percentage (%); and at least 1 of the following risk factors; Serum M protein >= 30 g/L, immunoglobulin (Ig)A SMM, immunoparesis with reduction of 2 uninvolved immunoglobulin isotypes (only IgA, IgM, and IgG should be considered in determination for immunoparesis; IgD and IgE are not considered in this assessment), serum involved: uninvolved FLC ratio >= 8 and less than (<) 100, or clonal BMPCs greater than (>) 50% to <60% with measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use highly effective method of contraception
• A woman of childbearing potential must have a negative serum or urine pregnancy test at screening within 14 days prior to randomization
• During the study and for 3 months after receiving the last dose of daratumumab, a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction

Exclusion Criteria:

• Multiple myeloma (MM), requiring treatment, defined by any of the following:

1. Bone lesions (1 or more osteolytic lesions on low-dose whole body computed tomography [LDCT], positron-emission tomography with computed tomography [PET-CT] or CT). Participants who have benign/post-traumatic bone lesions visible on screening images as well as previous imaging, may be considered for inclusion. Details (diagnosis, location, duration) on benign/post-traumatic pre-existing bone lesions that can be seen on the screening images (example [eg.], old fractures) and were also present on previous imaging are to be reported in the case report form (CRF)

2. 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]). Participants who have clinically stable hypercalcemia attributable to a disease other than multiple myeloma (eg, hyperparathyroidism) may be considered for inclusion after a case by case review by the medical monitor

3. Renal insufficiency, preferably determined by creatinine clearance less than (<)40 milliliter per minute (mL/min) measured or estimated using the Modification of Diet in Renal Disease (MDRD), or serum creatinine >177 micromole per liter (µmol/L). Participants who have clinically stable renal insufficiency attributable to a disease other than multiple myeloma (eg, glomerulonephritis) may be considered for inclusion after a case by case review by the medical monitor

4. Anemia, defined as hemoglobin <10 gram per deciliter (g/dL) or >2 g/dL below lower limit of normal or both; transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted. Participants who have clinically stable anemia attributable to a disease other than multiple myeloma (eg, thalassemia, vitamin B12 deficiency, iron deficiency) may be considered for inclusion after a case by case review by the medical monitor

5. Clonal BMPC percentage >=60%

6. Serum FLC ratio (involved:uninvolved) >=100 (the involved FLC must be >=100 mg/L)

7. More than 1 focal lesion >=5 millimeter (mm) in diameter by magnetic resonance imaging (MRI)

• Primary systemic amyloid light-chain (AL) (immunoglobulin light chain) amyloidosis
• Exposure to any of the following:

1. Prior exposure to daratumumab or prior exposure to other anti-Cluster of Differentiation 38 (anti-CD38) therapies

2. Prior exposure to approved or investigational treatments for SMM or MM (including but not limited to conventional chemotherapies, immunomodulatory agent [IMiDs], or proteasome inhibitor [PIs]). Stable standard dosing of bisphosphonate and denosumab as indicated for osteoporosis is acceptable

3. Exposure to investigational drug (including investigational vaccines) or invasive investigational medical device for any indication within 4 weeks or 5 half-lives, whichever is longer, before Cycle 1, Day 1

4. Ongoing treatment with corticosteroids with a dose >10 milligram (mg) prednisone or equivalent per day at the time of randomization; or >280 mg cumulative prednisone dose or equivalent for any 4-week period in the year prior to randomization

5. Ongoing treatment with other monoclonal antibodies (eg, infliximab, rituximab), immunomodulators (eg, abatacept, methotrexate, azathioprine, cyclosporine) or other treatments that are likely to interfere with the study procedures or results

• Received treatment (chemotherapy, surgery, et cetera [etc]) for a malignancy (other than SMM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion), which is considered cured with minimal risk of recurrence within 3 years
• Medical or psychiatric condition or disease (for example, active systemic disease [including presence of auto-antibodies], uncontrolled diabetes) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study
• Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies, hyaluronidase, or other human proteins, or their excipients, or known sensitivity to mammalian-derived products (including dairy allergy)

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Smoldering Multiple Myeloma

Intervention

Drug:
• Daratumumab SC: daratumumab + rHuPH20
Participants will receive daratumumab SC injection (daratumumab 1800 mg + rHuPH20 [2000 U/mL]) once weekly for Cycles 1 and 2 (Days 1, 8, 15, and 22 of each week), every 2 weeks for Cycle 3 to Cycle 6 (Days 1 and 15), and thereafter every 4 weeks (Day 1) until 39 cycles or up to 36 months or until confirmed disease progression, unacceptable toxicity or withdrawal from the study treatment, study termination or study completion. Each cycle is 28 days in duration.

Locations

Country	Name	City	State
Argentina	Hospital Aleman	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	CEMIC Saavedra	Ciudad de Buenos Aires
Argentina	Hospital Privado - Centro Medico de Cordoba	Cordoba
Argentina	Hospital Italiano de La Plata	La Plata
Argentina	Sanatorio Britanico de Rosario	Rosario
Australia	Austin Hospital	Heidelberg
Australia	Calvary Mater Newcastle Hospital	Waratah
Australia	The Perth Blood Institute	West Perth
Australia	Queen Elizabeth Hospital	Woodville
Belgium	ZNA	Antwerpen
Belgium	AZ St.-Jan Brugge-Oostende AV	Brugge
Belgium	UZBrussel	Brussel
Belgium	UZ Gent	Gent
Belgium	Virga Jessa Ziekenhuis	Hasselt
Belgium	Az Groeninge	Kortrijk
Brazil	Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN	Florianopolis
Brazil	Universidade Federal de Goias - Hospital das Clinicas da UFG	Goiania
Brazil	Instituto Joinvilense de Hematologia e Oncologia Ltda-Centro de Hematologia e Oncologia	Joinville
Brazil	Hospital das Clinicas de Porto Alegre	Porto Alegre
Brazil	Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)	Rio de Janeiro
Brazil	Hospital Sao Rafael	Salvador
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - Hospital de Base	Sao Jose do Rio Preto
Brazil	Instituto de Ensino e Pesquisa São Lucas	Sao Paulo
Brazil	Clinica Sao Germano	São Paulo
Brazil	Hospital Santa Cruz	São Paulo
Canada	Tom Baker Cancer Center, University of Calgary	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Ostrava	Ostrava
Czechia	Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni	Plzen
Czechia	Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie	Praha 2
Denmark	Aarhus University Hospital	Aarhus N.
Denmark	Ålborg Universitetshospital	Ålborg
Denmark	Rigshospitalet	Copenhagen
Denmark	Odense Universitetshospital	Odense C
France	CHU de Limoges - Fédération Hépatologie	Limoges
France	Chu Hotel Dieu	Nantes cedex 01
France	CHU de Bordeaux - Hospital Haut-Leveque	Pessac cedex
France	Centre hospitalier Lyon-Sud	Pierre Benite cedex
France	CHU De Poitiers	Poitiers
France	l'Hôpital Pontchaillou	Rennes
France	CHU Bretonneau	Tours Cedex 9
Germany	Helios Kliniken Berlin Buch Gmbh	Berlin
Germany	St. Barbara-Klinik Hamm GmbH	Hamm
Germany	Universitaetsklinikum Heidelberg Medizinische Klinik V	Heidelberg
Germany	Medizinische Klinik A	Muenster
Germany	Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,	Tübingen
Germany	Universitaetsklinikum Ulm	Ulm
Greece	Alexandra General Hospital of Athens	Athens Attica
Hungary	Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely	Budapest
Hungary	Semmelweis Egyetem I.Belgyogyaszati Klinika	Budapest
Hungary	Semmelweis Egyetem, I. Belgyogyaszati Klinika	Budapest N/a
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Israel	Haemek	Afula
Israel	Barzilai Medical Center	Ashkelon
Israel	Bnai Zion Medical Center	Haifa
Israel	Carmel Medical Center	Haifa
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Galilee Medical Center	Nahariya
Israel	Rabin Medical Center	Petah-Tiqva
Israel	Sheba Medical Center	Ramat Gan
Israel	Sourasky Medical Center	Tel-Aviv
Italy	Policlinico Sant'Orsola Malpighi	Bologna
Italy	Businco Cancer Hospital	Cagliari
Italy	A.O. Santa Croce e Carle	Cuneo
Italy	Ospedale S. Eugenio	Roma
Italy	Università di Roma 'La Sapienza' - Ospedale Umberto 1°	Roma
Italy	A.O.U. Città della Salute e della Scienza di Torino- Divisione di Ematologia	Torino
Italy	ASST dei Sette Laghi, Ospedale di Circolo e Fonazione Macchi	Varese
Japan	Fukuoka University Hospital	Fukuoka
Japan	Chugoku Central Hospital	Fukuyama
Japan	Ogaki Municipal Hospital	Gifu
Japan	Kobe City Medical Center General Hospital	Hyogo
Japan	Kagoshima University Hospital	Kagoshima
Japan	Kanazawa University Hospital	Kanazawa
Japan	National Hospital Organization Osaka Minami Medical Center	Kawachi-Nagano
Japan	National Hospital Organization Kumamoto Medical Center	Kumamoto-shi
Japan	Kurume University Hospital	Kurume
Japan	Kyoto Kuramaguchi Medical Center	Kyoto
Japan	National Hospital Organization Matsumoto Medical Center	Matsumoto
Japan	Matsuyama Red Cross Hospital	Matsuyama
Japan	Nagoya City University Hospital	Nagoya
Japan	Niigata Cancer Center Hospital	Niigata
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	National Hospital Organization Sendai Medical Center	Sendai-City
Japan	National Hospital Organization Shibukawa Medical Center	Shibukawa
Japan	Japanese Red Cross Medical Center	Shibuya
Mexico	iBiomed Research Unit	Aguascalientes
Mexico	JM Research, SC	Cuernavaca
Mexico	Centro de Investigación Farmacéutica Especializada	Guadalajara
Mexico	Centro de Atención e Investigación Clínica en Oncología	Merida
Mexico	Hospital Universitario de Nuevo León	Monterrey
Netherlands	Gelre Ziekenhuis	Apeldoorn
Netherlands	Haga ziekenhuis	Den Haag
Netherlands	Albert Schweitzer Ziekenhuis	Dordrecht
Netherlands	ETZ TweeSteden	Tilburg
Norway	Oslo University Hospital HF Ulleval sykehus	Oslo
Poland	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza	Brzozow
Poland	Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy	Bydgoszcz
Poland	Wojewodzki Szpital Specjalistyczny w Legnicy	Legnica
Poland	Clinical Research Center sp z o o MEDIC R s k	Poznan
Poland	Instytut Hematologii i Transfuzjologii	Warszawa
Russian Federation	Emergency Hospital of Dzerzhinsk	Dzerzhinsk
Russian Federation	City Clinical Hospital # 40	Moscow
Russian Federation	City clinical hospital n.a. S.P.Botkin	Moscow
Russian Federation	Nizhniy Novgorod Region Clinical Hospital	Nizhny Novgorod
Russian Federation	Perm Medical Sanitary Unit#1	Perm
Russian Federation	Republican Hospital n.a.V.A.Baranov	Petrozavodsk
Russian Federation	Ryazan Regional Clinical Hospital	Ryazan
Russian Federation	Clinical Research Institute of Hematology and Transfusiology	St-Petersburg
Russian Federation	Oncology Dispensary of Komi Republic	Syktyvkar
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona
Spain	Hosp. Clinic de Barcelona	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. Infanta Leonor	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp. Quiron Madrid Pozuelo	Pozuelo De Alarcon, Madrid
Spain	Hosp. Clinico Univ. de Salamanca	Salamanca
Spain	Hosp. Univ. Dr. Peset	Valencia
Sweden	Falu Lasarett	Falun
Sweden	Sunderby Sjukhus Medicinkliniken	Luelå
Sweden	Karolinska Universitetssjukhuset Huddinge	Stockholm
Turkey	Ankara Numune Egitim ve Arastirma Hastanesi	Ankara
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Trakya University Hospital	Edirne
Turkey	Istanbul University Istanbul Medical Faculty	Istanbul
Turkey	Erciyes University Medical Faculty	Kayseri
Turkey	On Dokuz Mayis University Medical Faculty Department of Hematology	Samsun
United Kingdom	Heart of England NHS Foundation Trust	Birmingham
United Kingdom	University Hospitals Bristol NHS Trust	Bristol
United Kingdom	Kent and Canterbury Hospital	Canterbury
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	Christie Hospital NHS Trust	Manchester
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Royal Stoke University Hospital	Stoke-On-Trent
United States	New York Oncology Hematology	Albany	New York
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Texas Oncology P.A.	Austin	Texas
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Levine Cancer Institute, Carolinas HealthCare System	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	VA North Texas Health Care System	Dallas	Texas
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	Miami Cancer Institute	Miami	Florida
United States	VA Southern Nevada Healthcare	North Las Vegas	Nevada
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Arizona Oncology Associates, PC - HAL	Phoenix	Arizona
United States	OHSU/CHM	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	University of Washington	Seattle	Washington
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Texas Oncology P.A.	Tyler	Texas
United States	Innovative Clinical Research, Inc.	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Mexico,  Netherlands,  Norway,  Poland,  Russian Federation,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	PFS is time from randomization to active MM according to International Myeloma Working Group (IMWG) criteria or death. Per IMWG criteria, active MM (SLiM-CRAB) is defined as: greater than or equal to (>=)60 percent (%) bone marrow plasma cells (BMPCs), free light chain (FLC) involved/uninvolved ratio >=100, greater than (>)1 focal bone lesions on magnetic resonance imaging (MRI), calcium elevation, renal insufficiency by creatinine clearance, anemia, or bone disease due to lytic bone lesions.	From the date of randomization to active multiple myeloma (MM) or the date of death, whichever occurs first (up to approximately 8 years)
Secondary	Time to Biochemical or Diagnostic (SLiM-CRAB) Progression	Time to biochemical or diagnostic progression is defined as the earlier of time to biochemical progression or diagnostic (SLiM-CRAB) progression. SLiM-CRAB is defined as >=60% bone marrow plasma cells, free light chain involved/uninvolved ratio >=100, >1 focal bone lesions on magnetic resonance imaging (MRI), calcium elevation, renal insufficiency by creatinine clearance, anemia, or bone disease due to lytic bone lesions.	Up to biochemical or diagnostic progression (up to approximately 8 years)
Secondary	Overall Response Rate (ORR)	ORR is defined as percentage of participants with partial response (PR) or better (very good partial response [VGPR], complete response [CR], and stringent complete response [sCR]) as defined by IMWG criteria. PR: >=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to less than (<)200 mg/24 hours; if serum and urine M-protein are not measurable, >=50% decrease in difference between involved and uninvolved free light chain (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, a >=50% reduction in BMPC, with baseline BMPC percentage >=30%. VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. CR: negative immunofixation on serum and urine, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4- color flow cytometry.	Up to approximately 8 years
Secondary	Complete Response (CR) Rate	CR rate was defined as the percentage of participants with a CR (or better [sCR]) as defined by the IMWG response criteria. IMWG criteria for CR: negative immunofixation on serum and urine, and <5% PCs in bone marrow. IMWG criteria for sCR: CR as defined above, plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.	Up to approximately 8 years
Secondary	Time to First-Line Treatment for Multiple Myeloma (MM)	Time to first-line treatment for MM was defined as the time from the date of randomization to the date of the first-line treatment given for MM (post disease progression).	Post-progressive disease (PD) follow-up, every 6 months until end of study (up to approximately 8 years)
Secondary	Progression-Free Survival on First-Line Treatment for MM (PFS2)	PFS2 is time from date of randomization to date of documented PD on first line treatment given for MM or death, whichever comes first. IMWG criteria for PD: >=25% from lowest response level in serum M-component (the absolute increase must be >=0.5 gram per deciliter [g/dL]) and/or in urine M-component (the absolute increase must be >=200 mg/24 hour); only in participants without measurable serum and urine M-protein levels: increase of >=25% in the difference between involved and uninvolved free light chain levels and the absolute increase must be >10 mg/dL. BMPC%: the absolute % must be >=10%; definite increase in size of existing bone lesions or soft tissue plasmacytomas; definite development of new bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 millimoles per liter [mmol/L]) that can be attributed solely to PC proliferative disorder.	Post-PD follow-up, every 6 months until end of study (up to approximately 8 years)
Secondary	Overall Survival (OS)	OS was defined as the time from the date of randomization to the date of the participant's death.	Throughout study, and at least every 3 months until PD; post-PD, every 6 months until end of study (up to approximately 8 years)
Secondary	Percentage of Participants who Progress to MM With Adverse Prognostic Features	Adverse prognostic features includes International Staging System Stage III (based on beta2 [ß2]-microglobulin >=5.5 milligram per liter [mg/L] [median survival 29 months]) and adverse cytogenetic characteristics.	At screening and PD (up to approximately 8 years)
Secondary	Serum Daratumumab Pharmacokinetic (PK) Concentration	PK concentration of Daratumumab will be measured.	Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)
Secondary	Maximum Observed Concentration (Cmax) of Daratumumab	The Cmax is the maximum observed plasma concentration of Daratumumab.	Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)
Secondary	Minimum Observed Concentration (Cmin) of Daratumumab	The Cmin is the minimum observed plasma concentration of Daratumumab.	Cycles 1 and 3: Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; end of the treatment (EOT: 28 days after the last daratumumab dose); and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)
Secondary	Number of Participants With Anti-daratumumab Antibodies	Participant's serum samples will be collected and screened for antibodies binding to daratumumab using validated immunoassay methods for evaluation of potential immunogenicity.	Cycles 1,3,5,7,12, and 24: Predose on Day 1; end of treatment (28 days after the last daratumumab dose), and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)
Secondary	Number of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies	Participant's plasma samples will be collected and screened for antibodies binding to rHuPH20 and will be assessed in confirmatory and titer assays as necessary for the rHuPH20 immunogenicity assessment.	Cycles 1,3,5,7,12, and 24: Predose on Day 1; end of treatment (28 days after the last daratumumab dose), and 8 weeks after the last daratumumab dose (up to approximately 3 years and 8 weeks)
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score	EORTC QLQ-C30 is a questionnaire to assess quality of life of cancer participants. It is composed of 30 items, multiitem measure (28 items) and 2 single-item measures. For the multiple item measure, 4 point scale is used and the score for each item range from "1 = not at all" to "4 = very much". Higher scores indicate worsening. The 2 single-item measure involves question about the overall health and overall quality of life which will be rated on a 7 point scale ranging from "1 = very poor" to "7 = excellent". Lower scores indicate worsening. Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning	Baseline, Weeks 12, 24, and 60, every year until end of treatment (EOT)/active monitoring, pre-PD follow-up (every year until end of study or PD), PD, and Months 3, 6, 12, and 18 post-PD (up to approximately 8 years)
Secondary	Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale	EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. EORTC QLQ-MY20 includes two scales: disease symptoms (6 questions) and future perspective (3 questions). Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the future perspective scale, a higher score indicates a better perspective of the future; and higher score for the disease symptoms scale indicates higher level of symptomatology.	Baseline, Weeks 12, 24, and 60, every year until end of treatment (EOT)/active monitoring, pre-PD follow-up (every year until end of study or PD), PD, and Months 3, 6, 12, and 18 post-PD (up to approximately 8 years)
Secondary	Change From Baseline in European Quality (EuroQoL) 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire	The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health).	Baseline, Weeks 12, 24, and 60, every year until end of treatment (EOT)/active monitoring, pre-PD follow-up (every year until end of study or PD), PD, and Months 3, 6, 12, and 18 post-PD (up to approximately 8 years)
Secondary	Duration of Response	Duration of response is defined as date of onset of first response (PR or better [VGPR, CR, sCR]) until date of disease progression or death. PR: >=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to <200 mg/24 hours; if the serum and urine M-protein are not measurable, >=50% decrease in difference between involved and uninvolved free light chain (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, a >=50% reduction in bone marrow PC, with baseline bone marrow PC percentage >=30%. VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. CR: negative immunofixation on serum and urine, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.	From the date of initial documentation of a response to the date of first documented evidence of PD (up to approximately 8 years)
Secondary	Time to Response	Time to response is defined as the time from randomization until onset of first response (PR or better [VGPR, CR, sCR]). PR: >=50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to <200 mg/24 hours; if the serum and urine M-protein are not measurable, >=50% decrease in difference between involved and uninvolved free light chain (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, a >=50% reduction in bone marrow PC, with baseline bone marrow PC percentage >=30%. VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours. CR: negative immunofixation on serum and urine, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.	Up to End of Treatment (up to approximately 39 cycles [each cycle of 28 days] or 36 months, whichever occurs first)