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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Smoldering Multiple Myeloma
• Intervention / Treatment: Drug: Daratumumab SC: daratumumab + rHuPH20

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 Type: Interventional
• Enrollment (Actual): 390
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1118AAT
    • Hospital Aleman
  • Buenos Aires, Argentina, C1199ABB
    • Hospital Italiano de Buenos Aires
  • Ciudad de Buenos Aires, Argentina, 1431
    • CEMIC Saavedra
  • Córdoba, Argentina, X5016KEH
    • Hospital Privado Centro Medico de Cordoba
  • La Plata, Argentina, B1900
    • Hospital Italiano de La Plata
  • Rosario, Argentina, 2000
    • Sanatorio Británico de Rosario
• Australia
  • Heidelberg, Australia, 3150 or 3084
    • Austin Hospital
  • Waratah, Australia, 2298
    • Calvary Mater Newcastle Hospital
  • West Perth, Australia, 6005
    • The Perth Blood Institute
  • Woodville, Australia, 5011
    • Queen Elizabeth Hospital
• Belgium
  • Antwerp, Belgium, 2060
    • ZNA
  • Bruges, Belgium, 8000
    • Algemeen Ziekenhuis Sint-Jan
  • Brussels, Belgium, 1090
    • UZBrussel
  • Ghent, Belgium, 9000
    • UZ Gent
  • Hasselt, Belgium, 3500
    • Virga Jessa Ziekenhuis
  • Kortrijk, Belgium, 8500
    • AZ Groeninge
• Brazil
  • Florianópolis, Brazil, 88034-000
    • Centro de Pesquisa e Ensino em Oncologia de Santa Catarina CEPEN
  • Goiânia, Brazil, 74605-020
    • Universidade Federal de Goias - Hospital das Clinicas da UFG
  • Joinville, Brazil, 89201-260
    • Instituto Joinvilense de Hematologia e Oncologia Ltda Centro de Hematologia e Oncologia
  • Porto Alegre, Brazil, 90035-003
    • Hospital das Clinicas de Porto Alegre
  • Rio de Janeiro, Brazil, 22775-002
    • Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
  • Salvador, Brazil, 41235-190
    • Hospital Sao Rafael
  • São José do Rio Preto, Brazil, 15090-000
    • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base
  • São Paulo, Brazil, 04122-000
    • Hospital Santa Cruz
  • São Paulo, Brazil, 01236-030
    • Instituto de Ensino e Pesquisa São Lucas
  • São Paulo, Brazil, 01455 010
    • Clinica Sao Germano
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J E Child Comprehensive Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Oshawa, Ontario, Canada, L1G-2B9
      • Lakeridge Health Oshawa
• Czechia
  • Hradec Králové, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Ostrava, Czechia, 70852
    • Fakultni Nemocnice Ostrava
  • Pilsen, Czechia, 323 00
    • Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
  • Prague, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
• Denmark
  • Aalborg, Denmark, 9000
    • Ålborg Universitetshospital
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Odense C, Denmark, 5000
    • Odense Universitetshospital
• France
  • Limoges, France, 87000
    • CHU de Limoges - Fédération Hépatologie
  • Lyon, France, 69002
    • Hospices Civils de Lyon HCL
  • Nantes, France, 44035
    • Chu Hotel Dieu
  • Pessac, France, 33604
    • CHU de Bordeaux - Hospital Haut-Leveque
  • Poitiers, France, 86021
    • Chu de Poitiers
  • Rennes, France, 35000
    • l Hopital Pontchaillou
  • Tours, France, 37044
    • Chu Bretonneau
• Germany
  • Berlin, Germany, 13125
    • Helios Kliniken Berlin Buch Gmbh
  • Hamm, Germany, 59073
    • St. Barbara-Klinik Hamm GmbH
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg Medizinische Klinik V
  • Münster, Germany, 48149
    • Medizinische Klinik A
  • Tübingen, Germany, 72076
    • Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,
  • Ulm, Germany, 89081
    • Universitaetsklinikum Ulm
• Greece
  • Athens Attica, Greece, 115 28
    • Alexandra General Hospital of Athens
• Hungary
  • Budapest, Hungary, 1088
    • Semmelweis Egyetem I.Belgyogyaszati Klinika
  • Budapest, Hungary, 1097
    • Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem, I. Belgyogyaszati Klinika
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
• Israel
  • Afula, Israel, 18101
    • Haemek
  • Ashkelon, Israel, 78741
    • Barzilai Medical Center
  • Haifa, Israel, 31048
    • Bnai Zion Medical Center
  • Haifa, Israel, 3436212
    • Carmel Medical Center
  • Haifa, Israel, 3525408
    • Rambam Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center
  • Nahariya, Israel, 22100
    • Galilee Medical Center
  • Petah Tikva, Israel, 49100
    • Rabin Medical Center
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center
• Italy
  • Bologna, Italy, 40138
    • Policlinico Sant'Orsola Malpighi
  • Cagliari, Italy, 09121
    • Businco Cancer Hospital
  • Cuneo, Italy, 12100
    • A.O. Santa Croce e Carle
  • Roma, Italy, 00144
    • Ospedale S. Eugenio
  • Rome, Italy, 00161
    • Università di Roma 'La Sapienza' - Ospedale Umberto 1°
  • Torino, Italy, 10126
    • A.O.U. Città della Salute e della Scienza di Torino- Divisione di Ematologia
  • Varese, Italy, 21100
    • ASST dei Sette Laghi, Ospedale di Circolo e Fonazione Macchi
• Japan
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Fukuyama, Japan, 720-0001
    • Chugoku Central Hospital
  • Gifu, Japan, 503-8502
    • Ogaki Municipal Hospital
  • Kagoshima, Japan, 890-8520
    • Kagoshima University Hospital
  • Kanazawa, Japan, 920 8641
    • Kanazawa University Hospital
  • Kawachi-Nagano, Japan, 586 8521
    • National Hospital Organization Osaka Minami Medical Center
  • Kobe, Japan, 650 0047
    • Kobe City Medical Center General Hospital
  • Kumamoto, Japan, 860-0008
    • National Hospital Organization Kumamoto Medical Center
  • Kurume, Japan, 830-0011
    • Kurume University Hospital
  • Kyoto, Japan, 603-8151
    • Kyoto Kuramaguchi Medical Center
  • 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
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Okayama, Japan, 701-1192
    • National Hospital Organization Okayama Medical Center
  • Sendai, Japan, 983-8520
    • National Hospital Organization Sendai Medical Center
  • Shibukawa, Japan, 377-0280
    • National Hospital Organization Shibukawa Medical Center
  • Shibuya City, Japan, 150-8935
    • Japanese Red Cross Medical Center
• Mexico
  • Aguascalientes, Mexico, 20121
    • iBiomed Research Unit
  • Cuernavaca, Mexico, 62290
    • JM Research, SC
  • Guadalajara, Mexico, 44160
    • Centro de Investigación Farmacéutica Especializada
  • Monterrey, Mexico, 64460
    • Hospital Universitario de Nuevo León
  • Mérida, Mexico, 97134
    • Centro de Atención e Investigación Clínica en Oncología
• Netherlands
  • Apeldoorn, Netherlands, 7334 DZ
    • Gelre Ziekenhuis
  • Dordrecht, Netherlands, 3318 AT
    • Albert Schweitzer Ziekenhuis
  • The Hague, Netherlands, 2545 AA
    • Haga ziekenhuis
  • Tilburg, Netherlands, 5042 AD
    • ETZ TweeSteden
• Norway
  • Oslo, Norway, 0450
    • Oslo University Hospital HF Ulleval sykehus
• Poland
  • Brzozów, Poland, 36-200
    • Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy
  • Legnica, Poland, 59-220
    • Wojewodzki Szpital Specjalistyczny W Legnicy
  • Poznan, Poland, 61 731
    • Clinical Research Center Sp z o o Medic R Sp k
  • Warsaw, Poland, 02-776
    • Instytut Hematologii I Transfuzjologii
• Russia
  • Dzerzhinsk, Russia, 606019
    • Emergency Hospital of Dzerzhinsk
  • Moscow, Russia, 125284
    • City clinical hospital n.a. S.P.Botkin
  • Moscow, Russia, 129301
    • City Clinical Hospital # 40
  • Nizhny Novgorod, Russia, 603126
    • Nizhniy Novgorod Region Clinical Hospital
  • Perm, Russia, 614078
    • Perm Medical Sanitary Unit#1
  • Petrozavodsk, Russia, 185019
    • Republican Hospital n.a.V.A.Baranov
  • Ryazan, Russia, 390003
    • Ryazan Regional Clinical Hospital
  • Saint Petersburg, Russia, 191024
    • Clinical Research Institute of Hematology and Transfusiology
  • Syktyvkar, Russia, 167904
    • Oncology Dispensary of Komi Republic
• Spain
  • Badalona, Spain, 08916
    • Hosp. Univ. Germans Trias I Pujol
  • Barcelona, Spain, 08036
    • Hosp Clinic de Barcelona
  • Barcelona, Spain, 8035
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28034
    • Hosp. Univ. Ramon Y Cajal
  • Madrid, Spain, 28007
    • Hosp. Gral. Univ. Gregorio Maranon
  • Madrid, Spain, 28031
    • Hosp. Univ. Infanta Leonor
  • Pamplona, Spain, 31008
    • Clinica Univ. de Navarra
  • Pozuelo de Alarcón, Spain, 28223
    • Hosp. Quiron Madrid Pozuelo
  • Salamanca, Spain, 37007
    • Hosp Clinico Univ de Salamanca
  • Valencia, Spain, 46017
    • Hosp. Univ. Dr. Peset
• Sweden
  • Falun, Sweden, 79182
    • Falu Lasarett
  • Luelå, Sweden, 97180
    • Sunderby Sjukhus Medicinkliniken
  • Stockholm, Sweden, 141 86
    • Karolinska Universitetssjukhuset Huddinge
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Ankara Numune Egitim ve Arastirma Hastanesi
  • Ankara, Turkey (Türkiye), 06620
    • Ankara Universitesi Tip Fakultesi Cebeci Arastirma ve Uygulama Hastanesi
  • Edirne, Turkey (Türkiye), 22030
    • Trakya Universitesi Tip Fakultesi Hastanesi
  • Istanbul, Turkey (Türkiye), 34093
    • Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
  • Kayseri, Turkey (Türkiye), 38039
    • Erciyes Universitesi Tip Fakultesi
  • Samsun, Turkey (Türkiye), 55280
    • Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Heart of England Nhs Foundation Trust
  • Bristol, United Kingdom, BS2 8ED
    • University Hospitals Bristol NHS Trust
  • Canterbury, United Kingdom, CT1 3NG
    • Kent and Canterbury Hospital
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital Nhs Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals Nhs Trust
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Royal Stoke University Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Oncology Associates, PC - HAL
  • California
    • Whittier, California, United States, 90805
      • Innovative Clinical Research Inc
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • East Jefferson General Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University
  • Nevada
    • North Las Vegas, Nevada, United States, 89086
      • VA Southern Nevada Healthcare
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute, Carolinas HealthCare System
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU/CHM
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology P A 1
    • Dallas, Texas, United States, 75216
      • VA North Texas Health Care System
    • Tyler, Texas, United States, 75702
      • Texas Oncology P A
  • Washington
    • Seattle, Washington, United States, 90805
      • University of Washington

Participation Criteria

Eligibility Criteria

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

Description

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)

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
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 Names: JNJ-54767414

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)	PFS was defined as the duration from the date of randomization to either progressive to multiple myeloma (MM), according to the International Myeloma Working Group (IMWG) diagnostic criteria for MM, or death due to any cause, whichever occurred first. Per IMWG criteria, active MM by SLiM-CRAB 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. Kaplan-Meier estimate was used.	From randomization (Day -5) up to 77 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to Biochemical or Diagnostic (SLiM-CRAB) Progression Per Computerized Algorithm Analyses	From randomization (Day -5) up to 8 years
Overall Response Rate (ORR)	From randomization (Day -5) up to 8 years
Complete Response (CR) Rate	From randomization (Day -5) up to 8 years
Time to First-Line Treatment for Multiple Myeloma	From randomization (Day -5) up to 8 years
Progression-Free Survival on First-Line Treatment for Multiple Myeloma (PFS2)	From randomization (Day -5) up to 8 years
Best Response on First-line Therapy for Multiple Myeloma	From randomization (Day -5) up to 8 years
Overall Survival (OS)	From randomization (Day -5) up to 8 years
Percentage of Participants Who Progressed to Multiple Myeloma With Adverse Prognostic Features	From randomization (Day -5) up to 8 years
Maximum Observed Serum Concentration (Cmax) 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, 37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
Minimum Observed Serum Concentration (Cmin) of Daratumumab	Cycles 1 and 3 : Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; EOT( 37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
Number of Participants With Anti-daratumumab Antibodies	Cycles 1 and 3 : Day 1 predose, and Day 4 postdose; Cycles 5, 7, 12, and 24: Day 1 predose; EOT (37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
Number of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies	Cycles 1, 3, 5, 7, 12, and 24 : Predose on Day 1; EOT (37.11 months); and 8 weeks after the last daratumumab dose (up to 38.11 months). Each Cycle was 28 days
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score	From Baseline (Day -35) up to 8 years
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	From Baseline (Day -35) up to 8 years
Change From Baseline in European Quality (EuroQoL) 5-Dimension 5-Level Health Status (EQ-5D-5L) Questionnaire Score	From Baseline (Day -35) up to 8 years
Duration of Response	From randomization (Day -5) up to 8 years
Time to Response	From randomization (Day -5) up to 8 years

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

• Dimopoulos MA, Voorhees PM, Schjesvold F, Cohen YC, Hungria V, Sandhu I, Lindsay J, Baker RI, Suzuki K, Kosugi H, Levin MD, Beksac M, Stockerl-Goldstein K, Oriol A, Mikala G, Garate G, Theunissen K, Spicka I, Mylin AK, Bringhen S, Uttervall K, Pula B, Medvedova E, Cowan AJ, Moreau P, Mateos MV, Goldschmidt H, Ahmadi T, Sha L, Cortoos A, Katz EG, Rousseau E, Li L, Dennis RM, Carson R, Rajkumar SV; AQUILA Investigators. Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma. N Engl J Med. 2025 May 8;392(18):1777-1788. doi: 10.1056/NEJMoa2409029. Epub 2024 Dec 9.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2017
• Primary Completion (Actual): May 1, 2024
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: September 29, 2017
• First Submitted That Met QC Criteria: September 29, 2017
• First Posted (Actual): October 4, 2017

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Hematologic Diseases; Immunoproliferative Disorders; Precancerous Conditions; Paraproteinemias; Blood Protein Disorders; Hypergammaglobulinemia; Hemic and Lymphatic Diseases; Smoldering Multiple Myeloma; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: CR108172; 54767414SMM3001 (Other Identifier: Janssen Research & Development, LLC); 2016-001205-16 (EudraCT Number); 2023-507143-11-00 (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