A Study of Subcutaneous Daratumumab Versus Active Monitoring in Participants With High-Risk Smoldering Multiple Myeloma
NCT ID: NCT03301220
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
390 participants
INTERVENTIONAL
2017-11-07
2026-06-30
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
No interventions assigned to this group
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.
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.
Interventions
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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 Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
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)
18 Years
ALL
No
Sponsors
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Janssen Research & Development, LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Janssen Research & Development, LLC Clinical Trial
Role: STUDY_DIRECTOR
Janssen Research & Development, LLC
Locations
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Arizona Oncology Associates, PC - HAL
Phoenix, Arizona, United States
Innovative Clinical Research Inc
Whittier, California, United States
Miami Cancer Institute
Miami, Florida, United States
Emory University
Atlanta, Georgia, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
East Jefferson General Hospital
Metairie, Louisiana, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Washington University
St Louis, Missouri, United States
VA Southern Nevada Healthcare
North Las Vegas, Nevada, United States
New York Oncology Hematology
Albany, New York, United States
Stony Brook University Medical Center
Stony Brook, New York, 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
OHSU/CHM
Portland, Oregon, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Texas Oncology P A
Austin, Texas, United States
VA North Texas Health Care System
Dallas, Texas, United States
Texas Oncology P A
Tyler, Texas, United States
University of Washington
Seattle, Washington, United States
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
Córdoba, , Argentina
Hospital Italiano de La Plata
La Plata, , Argentina
Sanatorio Britanico de Rosario
Rosario, , Argentina
Austin Hospital
Heidelberg, , Australia
Calvary Mater Newcastle Hospital
Waratah, , Australia
The Perth Blood Institute
West Perth, , Australia
Queen Elizabeth Hospital
Woodville, , Australia
ZNA
Antwerp, , Belgium
AZ St.-Jan Brugge-Oostende AV
Bruges, , Belgium
UZBrussel
Brussels, , Belgium
UZ Gent
Ghent, , Belgium
Virga Jessa Ziekenhuis
Hasselt, , Belgium
Az Groeninge
Kortrijk, , Belgium
Centro de Pesquisa e Ensino em Oncologia de Santa Catarina CEPEN
Florianópolis, , Brazil
Universidade Federal de Goias - Hospital das Clinicas da UFG
Goiânia, , 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
São José do Rio Preto, , Brazil
Instituto de Ensino e Pesquisa São Lucas
São Paulo, , Brazil
Clinica Sao Germano
São Paulo, , Brazil
Hospital Santa Cruz
São Paulo, , Brazil
Arthur J E Child Comprehensive Cancer Centre
Calgary, Alberta, Canada
Cross Cancer Institute
Edmonton, Alberta, Canada
Lakeridge Health Oshawa
Oshawa, Ontario, Canada
Fakultni nemocnice Hradec Kralove
Hradec Králové, , Czechia
Fakultni Nemocnice Ostrava
Ostrava, , Czechia
Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni
Pilsen, , Czechia
Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
Prague, , Czechia
Ålborg Universitetshospital
Aalborg, , Denmark
Aarhus University Hospital
Aarhus N, , Denmark
Rigshospitalet
Copenhagen, , Denmark
Odense Universitetshospital
Odense C, , Denmark
CHU de Limoges - Fédération Hépatologie
Limoges, , France
Chu Hotel Dieu
Nantes, , France
CHU de Bordeaux - Hospital Haut-Leveque
Pessac, , France
Centre hospitalier Lyon-Sud
Pierre-Bénite, , France
CHU De Poitiers
Poitiers, , France
l'Hôpital Pontchaillou
Rennes, , France
CHU Bretonneau
Tours, , France
Helios Kliniken Berlin Buch Gmbh
Berlin, , Germany
St. Barbara-Klinik Hamm GmbH
Hamm, , Germany
Universitaetsklinikum Heidelberg Medizinische Klinik V
Heidelberg, , Germany
Medizinische Klinik A
Münster, , Germany
Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,
Tübingen, , Germany
Universitaetsklinikum Ulm
Ulm, , Germany
Alexandra General Hospital of Athens
Athens Attica, , Greece
Semmelweis Egyetem, I. Belgyogyaszati Klinika
Budapest, , Hungary
Semmelweis Egyetem I.Belgyogyaszati Klinika
Budapest, , Hungary
Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely
Budapest, , Hungary
Debreceni Egyetem Klinikai Kozpont
Debrecen, , Hungary
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 Tikva, , Israel
Sheba Medical Center
Ramat Gan, , Israel
Sourasky Medical Center
Tel Aviv, , Israel
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, , Italy
Fukuoka University Hospital
Fukuoka, , Japan
Chugoku Central Hospital
Fukuyama, , Japan
Ogaki Municipal Hospital
Gifu, , Japan
Kagoshima University Hospital
Kagoshima, , Japan
Kanazawa University Hospital
Kanazawa, , Japan
National Hospital Organization Osaka Minami Medical Center
Kawachi-Nagano, , Japan
Kobe City Medical Center General Hospital
Kobe, , Japan
National Hospital Organization Kumamoto Medical Center
Kumamoto, , 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, , Japan
National Hospital Organization Shibukawa Medical Center
Shibukawa, , Japan
Japanese Red Cross Medical Center
Shibuya City, , Japan
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
Mérida, , Mexico
Hospital Universitario de Nuevo León
Monterrey, , Mexico
Gelre Ziekenhuis
Apeldoorn, , Netherlands
Albert Schweitzer Ziekenhuis
Dordrecht, , Netherlands
Haga ziekenhuis
The Hague, , Netherlands
ETZ TweeSteden
Tilburg, , Netherlands
Oslo University Hospital HF Ulleval sykehus
Oslo, , Norway
Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza
Brzozów, , 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 Sp k
Poznan, , Poland
Instytut Hematologii i Transfuzjologii
Warsaw, , Poland
Emergency Hospital of Dzerzhinsk
Dzerzhinsk, , Russia
City clinical hospital n.a. S.P.Botkin
Moscow, , Russia
City Clinical Hospital # 40
Moscow, , Russia
Nizhniy Novgorod Region Clinical Hospital
Nizhny Novgorod, , Russia
Perm Medical Sanitary Unit#1
Perm, , Russia
Republican Hospital n.a.V.A.Baranov
Petrozavodsk, , Russia
Ryazan Regional Clinical Hospital
Ryazan, , Russia
Clinical Research Institute of Hematology and Transfusiology
Saint Petersburg, , Russia
Oncology Dispensary of Komi Republic
Syktyvkar, , Russia
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 Alarcón, , Spain
Hosp Clinico Univ de Salamanca
Salamanca, , Spain
Hosp. Univ. Dr. Peset
Valencia, , Spain
Falu Lasarett
Falun, , Sweden
Sunderby Sjukhus Medicinkliniken
Luelå, , Sweden
Karolinska Universitetssjukhuset Huddinge
Stockholm, , Sweden
Ankara Numune Egitim ve Arastirma Hastanesi
Ankara, , Turkey (Türkiye)
Ankara University Medical Faculty
Ankara, , Turkey (Türkiye)
Trakya University Hospital
Edirne, , Turkey (Türkiye)
Istanbul University Istanbul Medical Faculty
Istanbul, , Turkey (Türkiye)
Erciyes University Medical Faculty
Kayseri, , Turkey (Türkiye)
Ondokuz Mayis University
Samsun, , Turkey (Türkiye)
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 Kingdom
Countries
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References
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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.
Other Identifiers
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54767414SMM3001
Identifier Type: OTHER
Identifier Source: secondary_id
2016-001205-16
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2023-507143-11-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
CR108172
Identifier Type: -
Identifier Source: org_study_id