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

NCT03301220 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 4 other identifiers: CR10817254767414SMM30012016-001205-162023-507143-11-00
• Study Type: interventional
• Target: 390
• Locations: 24 countries
• Sites: 163

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).

Conditions

Smoldering Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (17)

• 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

Study Arms (2)

Arm A: Active Monitoring

NO INTERVENTION

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.

Arm B: Daratumumab SC

EXPERIMENTAL

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

Interventions

Daratumumab SC: daratumumab + rHuPH20 DRUG

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.

Also known as: JNJ-54767414

Arm B: Daratumumab SC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Multiple myeloma (MM), requiring treatment, defined by any of the following:
• Clonal BMPC percentage \>=60%
• Serum FLC ratio (involved:uninvolved) \>=100 (the involved FLC must be \>=100 mg/L)
• 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:
• Prior exposure to daratumumab or prior exposure to other anti-Cluster of Differentiation 38 (anti-CD38) therapies
• 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
• 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
• 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
• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (163)

Arizona Oncology Associates, PC - HAL

Phoenix, Arizona, 85016, United States

Location

Innovative Clinical Research Inc

Whittier, California, 90805, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

East Jefferson General Hospital

Metairie, Louisiana, 70006, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

VA Southern Nevada Healthcare

North Las Vegas, Nevada, 89086, United States

Location

New York Oncology Hematology

Albany, New York, 12206, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Levine Cancer Institute, Carolinas HealthCare System

Charlotte, North Carolina, 28204, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

OHSU/CHM

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Texas Oncology P A 1

Austin, Texas, 78705, United States

Location

VA North Texas Health Care System

Dallas, Texas, 75216, United States

Location

Texas Oncology P A

Tyler, Texas, 75702, United States

Location

University of Washington

Seattle, Washington, 90805, United States

Location

Hospital Aleman

Buenos Aires, C1118AAT, Argentina

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1199ABB, Argentina

Location

CEMIC Saavedra

Ciudad de Buenos Aires, 1431, Argentina

Location

Hospital Privado Centro Medico de Cordoba

Córdoba, X5016KEH, Argentina

Location

Hospital Italiano de La Plata

La Plata, B1900, Argentina

Location

Sanatorio Britanico de Rosario

Rosario, 2000, Argentina

Location

Austin Hospital

Heidelberg, 3150 or 3084, Australia

Location

Calvary Mater Newcastle Hospital

Waratah, 2298, Australia

Location

The Perth Blood Institute

West Perth, 6005, Australia

Location

Queen Elizabeth Hospital

Woodville, 5011, Australia

Location

ZNA

Antwerp, 2060, Belgium

Location

Algemeen Ziekenhuis Sint-Jan

Bruges, 8000, Belgium

Location

UZBrussel

Brussels, 1090, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Virga Jessa Ziekenhuis

Hasselt, 3500, Belgium

Location

Az Groeninge

Kortrijk, 8500, Belgium

Location

Centro de Pesquisa e Ensino em Oncologia de Santa Catarina CEPEN

Florianópolis, 88034-000, Brazil

Location

Universidade Federal de Goias - Hospital das Clinicas da UFG

Goiânia, 74605-020, Brazil

Location

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

Joinville, 89201-260, Brazil

Location

Hospital das Clinicas de Porto Alegre

Porto Alegre, 90035-003, Brazil

Location

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

Rio de Janeiro, 22775-002, Brazil

Location

Hospital Sao Rafael

Salvador, 41235-190, Brazil

Location

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base

São José do Rio Preto, 15090-000, Brazil

Location

Instituto de Ensino e Pesquisa São Lucas

São Paulo, 01236-030, Brazil

Location

Clinica Sao Germano

São Paulo, 01455 010, Brazil

Location

Hospital Santa Cruz

São Paulo, 04122-000, Brazil

Location

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G-2B9, Canada

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Fakultni Nemocnice Ostrava

Ostrava, 70852, Czechia

Location

Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni

Pilsen, 323 00, Czechia

Location

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

Prague, 128 08, Czechia

Location

Ålborg Universitetshospital

Aalborg, 9000, Denmark

Location

Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Odense Universitetshospital

Odense C, 5000, Denmark

Location

CHU de Limoges - Fédération Hépatologie

Limoges, 87000, France

Location

Hospices Civils de Lyon HCL

Lyon, 69002, France

Location

Chu Hotel Dieu

Nantes, 44035, France

Location

CHU de Bordeaux - Hospital Haut-Leveque

Pessac, 33604, France

Location

CHU De Poitiers

Poitiers, 86021, France

Location

l Hopital Pontchaillou

Rennes, 35000, France

Location

CHU Bretonneau

Tours, 37044, France

Location

Helios Kliniken Berlin Buch Gmbh

Berlin, 13125, Germany

Location

St. Barbara-Klinik Hamm GmbH

Hamm, 59073, Germany

Location

Universitaetsklinikum Heidelberg Medizinische Klinik V

Heidelberg, 69120, Germany

Location

Medizinische Klinik A

Münster, 48149, Germany

Location

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

Tübingen, 72076, Germany

Location

Universitaetsklinikum Ulm

Ulm, 89081, Germany

Location

Alexandra General Hospital of Athens

Athens Attica, 115 28, Greece

Location

Semmelweis Egyetem, I. Belgyogyaszati Klinika

Budapest, 1083, Hungary

Location

Semmelweis Egyetem I.Belgyogyaszati Klinika

Budapest, 1088, Hungary

Location

Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely

Budapest, 1097, Hungary

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Haemek

Afula, 18101, Israel

Location

Barzilai Medical Center

Ashkelon, 78741, Israel

Location

Bnai Zion Medical Center

Haifa, 31048, Israel

Location

Carmel Medical Center

Haifa, 3436212, Israel

Location

Rambam Medical Center

Haifa, 3525408, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Galilee Medical Center

Nahariya, 22100, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Policlinico Sant'Orsola Malpighi

Bologna, 40138, Italy

Location

Businco Cancer Hospital

Cagliari, 09121, Italy

Location

A.O. Santa Croce e Carle

Cuneo, 12100, Italy

Location

Ospedale S. Eugenio

Roma, 00144, Italy

Location

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

Rome, 00161, Italy

Location

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

Torino, 10126, Italy

Location

ASST dei Sette Laghi, Ospedale di Circolo e Fonazione Macchi

Varese, 21100, Italy

Location

Fukuoka University Hospital

Fukuoka, 814-0180, Japan

Location

Chugoku Central Hospital

Fukuyama, 720-0001, Japan

Location

Ogaki Municipal Hospital

Gifu, 503-8502, Japan

Location

Kagoshima University Hospital

Kagoshima, 890-8520, Japan

Location

Kanazawa University Hospital

Kanazawa, 920 8641, Japan

Location

National Hospital Organization Osaka Minami Medical Center

Kawachi-Nagano, 586 8521, Japan

Location

Kobe City Medical Center General Hospital

Kobe, 650 0047, Japan

Location

National Hospital Organization Kumamoto Medical Center

Kumamoto, 860-0008, Japan

Location

Kurume University Hospital

Kurume, 830-0011, Japan

Location

Kyoto Kuramaguchi Medical Center

Kyoto, 603-8151, Japan

Location

National Hospital Organization Matsumoto Medical Center

Matsumoto, 399-8701, Japan

Location

Matsuyama Red Cross Hospital

Matsuyama, 790-8524, Japan

Location

Nagoya City University Hospital

Nagoya, 467 8602, Japan

Location

Niigata Cancer Center Hospital

Niigata, 951-8566, Japan

Location

National Hospital Organization Okayama Medical Center

Okayama, 701-1192, Japan

Location

National Hospital Organization Sendai Medical Center

Sendai, 983-8520, Japan

Location

National Hospital Organization Shibukawa Medical Center

Shibukawa, 377-0280, Japan

Location

Japanese Red Cross Medical Center

Shibuya City, 150-8935, Japan

Location

iBiomed Research Unit

Aguascalientes, 20121, Mexico

Location

JM Research, SC

Cuernavaca, 62290, Mexico

Location

Centro de Investigación Farmacéutica Especializada

Guadalajara, 44160, Mexico

Location

Centro de Atención e Investigación Clínica en Oncología

Mérida, 97134, Mexico

Location

Hospital Universitario de Nuevo León

Monterrey, 64460, Mexico

Location

Gelre Ziekenhuis

Apeldoorn, 7334 DZ, Netherlands

Location

Albert Schweitzer Ziekenhuis

Dordrecht, 3318 AT, Netherlands

Location

Haga ziekenhuis

The Hague, 2545 AA, Netherlands

Location

ETZ TweeSteden

Tilburg, 5042 AD, Netherlands

Location

Oslo University Hospital HF Ulleval sykehus

Oslo, 0450, Norway

Location

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza

Brzozów, 36-200, Poland

Location

Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy

Bydgoszcz, 85-168, Poland

Location

Wojewodzki Szpital Specjalistyczny w Legnicy

Legnica, 59-220, Poland

Location

Clinical Research Center Sp z o o Medic R Sp k

Poznan, 61 731, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

Emergency Hospital of Dzerzhinsk

Dzerzhinsk, 606019, Russia

Location

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

Moscow, 125284, Russia

Location

City Clinical Hospital # 40

Moscow, 129301, Russia

Location

Nizhniy Novgorod Region Clinical Hospital

Nizhny Novgorod, 603126, Russia

Location

Perm Medical Sanitary Unit#1

Perm, 614078, Russia

Location

Republican Hospital n.a.V.A.Baranov

Petrozavodsk, 185019, Russia

Location

Ryazan Regional Clinical Hospital

Ryazan, 390003, Russia

Location

Clinical Research Institute of Hematology and Transfusiology

Saint Petersburg, 191024, Russia

Location

Oncology Dispensary of Komi Republic

Syktyvkar, 167904, Russia

Location

Hosp. Univ. Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007, Spain

Location

Hosp. Univ. Infanta Leonor

Madrid, 28031, Spain

Location

Hosp. Univ. Ramon Y Cajal

Madrid, 28034, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hosp. Quiron Madrid Pozuelo

Pozuelo de Alarcón, 28223, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Hosp. Univ. Dr. Peset

Valencia, 46017, Spain

Location

Falu Lasarett

Falun, 79182, Sweden

Location

Sunderby Sjukhus Medicinkliniken

Luelå, 97180, Sweden

Location

Karolinska Universitetssjukhuset Huddinge

Stockholm, 141 86, Sweden

Location

Ankara Numune Egitim ve Arastirma Hastanesi

Ankara, 06230, Turkey (Türkiye)

Location

Ankara Universitesi Tip Fakultesi Cebeci Arastirma ve Uygulama Hastanesi

Ankara, 06620, Turkey (Türkiye)

Location

Trakya Universitesi Tip Fakultesi Hastanesi

Edirne, 22030, Turkey (Türkiye)

Location

Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi

Istanbul, 34093, Turkey (Türkiye)

Location

Erciyes Universitesi Tip Fakultesi

Kayseri, 38039, Turkey (Türkiye)

Location

Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi

Samsun, 55280, Turkey (Türkiye)

Location

Heart of England NHS Foundation Trust

Birmingham, B9 5SS, United Kingdom

Location

University Hospitals Bristol NHS Trust

Bristol, BS2 8ED, United Kingdom

Location

Kent and Canterbury Hospital

Canterbury, CT1 3NG, United Kingdom

Location

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

Christie Hospital NHS Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

Royal Stoke University Hospital

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

Location

Related Publications (1)

• 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.

  PMID: 39652675 DERIVED

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 4, 2017
• Study Start: November 7, 2017
• Primary Completion: May 1, 2024
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 13, 2026
• Results First Posted: December 23, 2025

Record last verified: 2026-04

Locations

BE (6); DE (6); US (23); CA (3); FR (7); NO (1); IL (10); GR (1); HU (4); AU (4); RU (9); CZ (4); PL (5); NL (4); GB (7); BR (10); JP (18); ME (5); AR (6); SE (3); ES (10); TU (6); IT (7); DK (4)