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

• ClinicalTrials.gov Identifier: NCT03301220
• Recruitment Status: Active, not recruiting
• First Posted: October 4, 2017
• Last Update Posted: March 15, 2023
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Smoldering Multiple Myeloma	Drug: Daratumumab SC: daratumumab + rHuPH20	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 390 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Multicenter Study of Subcutaneous Daratumumab Versus Active Monitoring in Subjects With High-Risk Smoldering Multiple Myeloma
• Actual Study Start Date: November 7, 2017
• Estimated Primary Completion Date: August 15, 2023
• Estimated Study Completion Date: December 22, 2025

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Arm A: Active Monitoring; Participants randomized to active monitoring will receive no study medication, but will undergo the same disease evaluations at the same frequency as participants randomized to daratumumab.
Experimental: Arm B: Daratumumab SC; Participants will receive 1800 milligram (mg) of daratumumab co-formulated with 2000 units per milliliter (U/mL) of recombinant human hyaluronidase (rHuPH20) by subcutaneous (SC) injection 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.	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.; Other Name: JNJ-54767414

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: From the date of randomization to active multiple myeloma (MM) or the date of death, whichever occurs first (up to approximately 8 years) ]
   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.

Secondary Outcome Measures :

1. Time to Biochemical or Diagnostic (SLiM-CRAB) Progression [ Time Frame: Up to biochemical or diagnostic progression (up to approximately 8 years) ]
   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.
2. Overall Response Rate (ORR) [ Time Frame: Up to approximately 8 years ]
   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.
3. Complete Response (CR) Rate [ Time Frame: Up to approximately 8 years ]
   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.
4. Time to First-Line Treatment for Multiple Myeloma (MM) [ Time Frame: Post-progressive disease (PD) follow-up, every 6 months until end of study (up to approximately 8 years) ]
   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).
5. Progression-Free Survival on First-Line Treatment for MM (PFS2) [ Time Frame: Post-PD follow-up, every 6 months until end of study (up to approximately 8 years) ]
   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.
6. Overall Survival (OS) [ Time Frame: Throughout study, and at least every 3 months until PD; post-PD, every 6 months until end of study (up to approximately 8 years) ]
   OS was defined as the time from the date of randomization to the date of the participant's death.
7. Percentage of Participants who Progress to MM With Adverse Prognostic Features [ Time Frame: At screening and PD (up to approximately 8 years) ]
   Adverse prognostic features includes International Staging System Stage III (based on beta2 [β2]-microglobulin >=5.5 milligram per liter [mg/L] [median survival 29 months]) and adverse cytogenetic characteristics.
8. Serum Daratumumab Pharmacokinetic (PK) Concentration [ Time Frame: 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) ]
   PK concentration of Daratumumab will be measured.
9. Maximum Observed Concentration (Cmax) of Daratumumab [ Time Frame: 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) ]
   The Cmax is the maximum observed plasma concentration of Daratumumab.
10. Minimum Observed Concentration (Cmin) of Daratumumab [ Time Frame: 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) ]
    The Cmin is the minimum observed plasma concentration of Daratumumab.
11. Number of Participants With Anti-daratumumab Antibodies [ Time Frame: 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) ]
    Participant's serum samples will be collected and screened for antibodies binding to daratumumab using validated immunoassay methods for evaluation of potential immunogenicity.
12. Number of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies [ Time Frame: 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) ]
    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.
13. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score [ Time Frame: 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) ]
    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
14. 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 [ Time Frame: 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) ]
    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.
15. Change From Baseline in European Quality (EuroQoL) 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire [ Time Frame: 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) ]
    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).
16. Duration of Response [ Time Frame: From the date of initial documentation of a response to the date of first documented evidence of PD (up to approximately 8 years) ]
    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.
17. Time to Response [ Time Frame: Up to End of Treatment (up to approximately 39 cycles [each cycle of 28 days] or 36 months, whichever occurs first) ]
    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.

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United States, Arizona

Arizona Oncology Associates, PC - HAL

Phoenix, Arizona, United States, 85016

United States, California

Innovative Clinical Research, Inc.

Whittier, California, United States, 90805

United States, Florida

Miami Cancer Institute

Miami, Florida, United States, 33176

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Iowa

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States, 52242

United States, Louisiana

East Jefferson General Hospital

Metairie, Louisiana, United States, 70006

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215-5418

United States, Michigan

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110

United States, Nevada

VA Southern Nevada Healthcare

North Las Vegas, Nevada, United States, 89086

United States, New York

New York Oncology Hematology

Albany, New York, United States, 12206

Stony Brook University Medical Center

Stony Brook, New York, United States, 11794

United States, North Carolina

University of North Carolina

Chapel Hill, North Carolina, United States, 27599

Levine Cancer Institute, Carolinas HealthCare System

Charlotte, North Carolina, United States, 28204

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

The Ohio State University

Columbus, Ohio, United States, 43210

United States, Oregon

OHSU/CHM

Portland, Oregon, United States, 97239

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

United States, Texas

Texas Oncology P.A.

Austin, Texas, United States, 78705

VA North Texas Health Care System

Dallas, Texas, United States, 75216

Texas Oncology P.A.

Tyler, Texas, United States, 75702

United States, Washington

University of Washington

Seattle, Washington, United States, 90805

Argentina

Hospital Aleman

Buenos Aires, Argentina, C1118AAT

Hospital Italiano de Buenos Aires

Buenos Aires, Argentina, C1199ABD

CEMIC Saavedra

Ciudad de Buenos Aires, Argentina, 1431

Hospital Privado - Centro Medico de Cordoba

Cordoba, Argentina, X5016KEH

Hospital Italiano de La Plata

La Plata, Argentina, B1900AXI

Sanatorio Britanico de Rosario

Rosario, Argentina, 2000

Australia

Austin Hospital

Heidelberg, Australia, 3150 or 3084

Calvary Mater Newcastle Hospital

Waratah, Australia, 2298

The Perth Blood Institute

West Perth, Australia, 6005

Queen Elizabeth Hospital

Woodville, Australia, 5011

Belgium

ZNA

Antwerpen, Belgium, 2060

AZ St.-Jan Brugge-Oostende AV

Brugge, Belgium, 8000

UZBrussel

Brussel, Belgium, 1090

UZ Gent

Gent, Belgium, 9000

Virga Jessa Ziekenhuis

Hasselt, Belgium, 3500

Az Groeninge

Kortrijk, Belgium, 8500

Brazil

Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN

Florianopolis, Brazil, 88034-000

Universidade Federal de Goias - Hospital das Clinicas da UFG

Goiânia, Brazil, 74605-020

Instituto Joinvilense de Hematologia e Oncologia Ltda - Centro de Hematologia e Oncologia

Joinville, Brazil, 89201-260

Hospital das Clinicas de Porto Alegre

Porto Alegre, Brazil, 90035-003

Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)

Rio de Janeiro, Brazil, 22775-001

Hospital Sao Rafael

Salvador, Brazil, 41235-190

Fundação Faculdade Regional de Medicina de São José do Rio Preto - Hospital de Base

Sao Jose do Rio Preto, Brazil, 15090-000

Instituto de Ensino e Pesquisa São Lucas

Sao Paulo, Brazil, 01236-030

Clinica Sao Germano

São Paulo, Brazil, 01455-010

Hospital Santa Cruz

São Paulo, Brazil, 04122-000

Canada, Alberta

Tom Baker Cancer Center, University of Calgary

Calgary, Alberta, Canada, T2N 4N2

Cross Cancer Institute

Edmonton, Alberta, Canada, T6G 1Z2

Canada, Ontario

Lakeridge Health Oshawa

Oshawa, Ontario, Canada, L1G-2B9

Czechia

Fakultni nemocnice Hradec Kralove

Hradec Kralove, Czechia, 500 05

Fakultni nemocnice Ostrava

Ostrava, Czechia, 70852

Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni

Plzen, Czechia, 323 00

Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie

Praha 2, Czechia, 128 08

Denmark

Aarhus University Hospital

Aarhus N., Denmark, 8200

Rigshospitalet

Copenhagen, Denmark, 2100

Odense Universitetshospital

Odense C, Denmark, 5000

Ålborg Universitetshospital

Ålborg, Denmark, 9000

France

CHU de Limoges - Fédération Hépatologie

Limoges, France, 87000

Chu Hotel Dieu

Nantes cedex 01, France, 44035

CHU de Bordeaux - Hospital Haut-Leveque

Pessac cedex, France, 33604

Centre hospitalier Lyon-Sud

Pierre Benite cedex, France, 69495

CHU De Poitiers

Poitiers, France, 86021

l'Hôpital Pontchaillou

Rennes, France, 35033

CHU Bretonneau

Tours Cedex 9, France, 37044

Germany

Helios Kliniken Berlin Buch Gmbh

Berlin, Germany, 13125

St. Barbara-Klinik Hamm GmbH

Hamm, Germany, 59073

Universitaetsklinikum Heidelberg Medizinische Klinik V

Heidelberg, Germany, 69120

Medizinische Klinik A

Muenster, Germany, 48149

Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,

Tübingen, Germany, 72076

Universitaetsklinikum Ulm

Ulm, Germany, 89081

Greece

Alexandra General Hospital of Athens

Athens Attica, Greece, 115 28

Hungary

Semmelweis Egyetem, I. Belgyogyaszati Klinika

Budapest N/a, Hungary, 1083

Semmelweis Egyetem I.Belgyogyaszati Klinika

Budapest, Hungary, 1088

Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet, Szent László Telephely

Budapest, Hungary, 1097

Debreceni Egyetem Klinikai Kozpont

Debrecen, Hungary, 4032

Israel

Haemek

Afula, Israel, 18101

Barzilai Medical Center

Ashkelon, Israel, 78741

Bnai Zion Medical Center

Haifa, Israel, 31048

Carmel Medical Center

Haifa, Israel, 3436212

Rambam Medical Center

Haifa, Israel, 3525408

Hadassah Medical Center

Jerusalem, Israel, 9112001

Galilee Medical Center

Nahariya, Israel, 22100

Rabin Medical Center

Petah-Tiqva, Israel, 49100

Sheba Medical Center

Ramat Gan, Israel, 52621

Sourasky Medical Center

Tel-Aviv, Israel, 6423906

Italy

Policlinico Sant'Orsola Malpighi

Bologna, Italy, 40138

Businco Cancer Hospital

Cagliari, Italy, 09121

A.O. Santa Croce e Carle

Cuneo, Italy, 12100

Ospedale S. Eugenio

Roma, Italy, 00144

Università di Roma 'La Sapienza' - Ospedale Umberto 1°

Roma, Italy, 00161

A.O.U. Città della Salute e della Scienza di Torino- Divisione di Ematologia

Torino, Italy, 10126

ASST dei Sette Laghi, Ospedale di Circolo e Fonazione Macchi

Varese, Italy, 21100

Japan

Fukuoka University Hospital

Fukuoka, Japan, 814-0180

Chugoku Central Hospital

Fukuyama, Japan, 720-0001

Ogaki Municipal Hospital

Gifu, Japan, 503-8502

Kobe City Medical Center General Hospital

Hyogo, Japan, 650-0047

Kagoshima University Hospital

Kagoshima, Japan, 890-8520

Kanazawa University Hospital

Kanazawa, Japan, 920-8641

National Hospital Organization Osaka Minami Medical Center

Kawachi-Nagano, Japan, 586-8521

National Hospital Organization Kumamoto Medical Center

Kumamoto-shi, Japan, 860-0008

Kurume University Hospital

Kurume, Japan, 830-0011

Kyoto Kuramaguchi Medical Center

Kyoto, Japan, 603-8151

National Hospital Organization Matsumoto Medical Center

Matsumoto, Japan, 399-8701

Matsuyama Red Cross Hospital

Matsuyama, Japan, 790-8524

Nagoya City University Hospital

Nagoya, Japan, 467-8602

Niigata Cancer Center Hospital

Niigata, Japan, 951-8566

National Hospital Organization Okayama Medical Center

Okayama, Japan, 701-1192

National Hospital Organization Sendai Medical Center

Sendai-City, Japan, 983-8520

National Hospital Organization Shibukawa Medical Center

Shibukawa, Japan, 377-0280

Japanese Red Cross Medical Center

Shibuya, Japan, 150-8935

Mexico

iBiomed Research Unit

Aguascalientes, Mexico, 20121

JM Research, SC

Cuernavaca, Mexico, 62290

Centro de Investigación Farmacéutica Especializada

Guadalajara, Mexico, 44160

Centro de Atención e Investigación Clínica en Oncología

Merida, Mexico, 97134

Hospital Universitario de Nuevo León

Monterrey, Mexico, 64460

Netherlands

Gelre Ziekenhuis

Apeldoorn, Netherlands, 7334 DZ

Haga ziekenhuis

Den Haag, Netherlands, 2545 AA

Albert Schweitzer Ziekenhuis

Dordrecht, Netherlands, 3318 AT

ETZ TweeSteden

Tilburg, Netherlands, 5042 AD

Norway

Oslo University Hospital HF Ullevål sykehus

Oslo, Norway, 0450

Poland

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza

Brzozow, Poland, 36-200

Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy

Bydgoszcz, Poland, 85-168

Wojewodzki Szpital Specjalistyczny w Legnicy

Legnica, Poland, 59-220

Clinical Research Center sp. z o.o MEDIC-R s.k.

Poznań, Poland, 60-848

Instytut Hematologii i Transfuzjologii

Warszawa, Poland, 02-776

Russian Federation

Emergency Hospital of Dzerzhinsk

Dzerzhinsk, Russian Federation, 606019

City clinical hospital n.a. S.P.Botkin

Moscow, Russian Federation, 125284

City Clinical Hospital # 40

Moscow, Russian Federation, 129301

Nizhniy Novgorod Region Clinical Hospital

Nizhny Novgorod, Russian Federation, 603126

Perm Medical Sanitary Unit#1

Perm, Russian Federation, 614078

Republican Hospital n.a.V.A.Baranov

Petrozavodsk, Russian Federation, 185019

Ryazan Regional Clinical Hospital

Ryazan, Russian Federation, 390003

Clinical Research Institute of Hematology and Transfusiology

St-Petersburg, Russian Federation, 191024

Oncology Dispensary of Komi Republic

Syktyvkar, Russian Federation, 167904

Spain

Hosp. Univ. Germans Trias I Pujol

Badalona, Spain, 08916

Hosp. Clinic I Provincial de Barcelona

Barcelona, Spain, 08036

Hosp. Univ. Vall D Hebron

Barcelona, Spain, 8035

Hosp. Gral. Univ. Gregorio Marañon

Madrid, Spain, 28007

Hosp. Univ. Infanta Leonor

Madrid, Spain, 28031

Hosp. Univ. Ramon Y Cajal

Madrid, Spain, 28034

Clinica Univ. De Navarra

Pamplona, Spain, 31008

Hosp. Quiron Madrid Pozuelo

Pozuelo De Alarcon, Madrid, Spain, 28223

Hosp. Clinico Univ. de Salamanca

Salamanca, Spain, 37007

Hosp. Univ. Dr. Peset

Valencia, Spain, 46017

Sweden

Falu Lasarett

Falun, Sweden, 79182

Sunderby Sjukhus Medicinkliniken

Luelå, Sweden, 97180

Karolinska Universitetssjukhuset Huddinge

Stockholm, Sweden, 141 86

Turkey

Ankara Numune Egitim ve Arastirma Hastanesi

Ankara, Turkey, 06230

Ankara University Medical Faculty

Ankara, Turkey, 6100

Trakya University Hospital

Edirne, Turkey, 22030

Istanbul University Istanbul Medical Faculty

Istanbul, Turkey, 34093

Erciyes University Medical Faculty

Kayseri, Turkey, 38030

On Dokuz Mayis University Medical Faculty Department of Hematology

Samsun, Turkey, 55139

United Kingdom

Heart of England NHS Foundation Trust

Birmingham, United Kingdom, B9 5SS

University Hospitals Bristol NHS Trust

Bristol, United Kingdom, BS2 8ED

Kent and Canterbury Hospital

Canterbury, United Kingdom, CT1 3NG

St Bartholomew's Hospital

London, United Kingdom, EC1A 7BE

Christie Hospital NHS Trust

Manchester, United Kingdom, M20 4BX

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom, NG5 1PB

Royal Stoke University Hospital

Stoke-On-Trent, United Kingdom, ST4 6QG

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

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

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT03301220
• Other Study ID Numbers: CR108172; 54767414SMM3001 ( Other Identifier: Janssen Research & Development, LLC ); 2016-001205-16 ( EudraCT Number )
• First Posted: October 4, 2017
• Last Update Posted: March 15, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Hypergammaglobulinemia; Daratumumab; Antineoplastic Agents