Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab

NCT03871829 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: CR1085982018-004185-3454767414MMY2065
• Study Type: interventional
• Target: 88
• Locations: 13 countries
• Sites: 108

Brief Summary

The purpose of this study is to compare the efficacy (rate of very good partial response \[VGPR\] or better as best response as defined by the International Myeloma Working Group \[IMWG\] criteria) of daratumumab subcutaneous (Dara-SC) in combination with carfilzomib and dexamethasone (Kd) with the efficacy of Kd in participants with relapsed refractory multiple myeloma who were previously exposed to daratumumab to evaluate daratumumab retreatment.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response

  Percentage of participants achieving VGPR or better response were reported. VGPR or better rate was defined as the percentage of participants achieving VGPR, complete response (CR), or stringent complete response (sCR) in accordance with the International Myeloma Working Group (IMWG) criteria, during or after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than or equal to (\>=) 90 percent (%) reduction in serum M-protein plus urine M-protein less than (\<) 100 milligram (mg)/24 hours; for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and \<5% PCs in bone marrow; for sCR: CR plus normal free light chain (FLC) ratio, and Absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4- color flow cytometry.

  Up to 3 years and 4 months

Secondary Outcomes (9)

• Overall Response Rate (ORR)

  Up to 3 years and 7 months

• Percentage of Participants Achieving Complete Response (CR) or Better

  Up to 3 years and 7 months

• Progression Free Survival (PFS)

  Up to 3 years and 7 months

• Overall Survival (OS)

  Up to 3 years and 7 months

• Percentage of Participants With Negative Minimal Residual Disease (MRD)

  Up to 3 years and 7 months

Study Arms (2)

Arm A: Carfilzomib+Dexamethasone (Kd)

ACTIVE COMPARATOR

Participants will receive carfilzomib 20 milligram per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1 and then 70 mg/m\^2 on Days 8 and 15 of Cycle 1 and thereafter on Days 1, 8, 15 of Cycle 2 onwards. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days.

Drug: Carfilzomib 20 mg/m^2; Drug: Carfilzomib 70 mg/m^2; Drug: Dexamethasone 40 mg; Drug: Dexamethasone 20 mg

Arm B: Dara-SC in combination with Kd (DKd)

EXPERIMENTAL

Participants will receive daratumumab subcutaneous (Dara-SC) 1800 mg by SC injection on Days 1, 8, 15, 22 for Cycle 1 and 2, Days 1 and 15 for Cycle 3-6, Day 1 for Cycle 7 onwards. Participants will receive carfilzomib 20 mg/m\^2 IV on Cycle 1 Day 1 and then 70 mg/m\^2 on Day 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2. Participants will receive dexamethasone 20 mg on Cycle 1 Day 1, a second dose of 20 milligram (mg) will be given on Cycle 1 Day 2 and 40 mg IV or orally on Days 8, 15, 22 for Cycle 1. Patients will then receive dexamethasone 40mg on days 1, 8, 15 and 22 for cycles 2-9, then on Days 1, 8, 15 for Cycle 10 onwards, until death, intolerable toxicity, start of a new treatment for multiple myeloma, withdrawal of consent, or end of the study. The total duration of each cycle is 28 Days.

Drug: Carfilzomib 20 mg/m^2; Drug: Carfilzomib 70 mg/m^2; Drug: Dexamethasone 40 mg; Drug: Dara-SC 1800 mg; Drug: Dexamethasone 20 mg

Interventions

Carfilzomib 20 mg/m^2 DRUG

Carfilzomib 20 mg/m\^2 will be administered intravenously (IV).

Arm A: Carfilzomib+Dexamethasone (Kd); Arm B: Dara-SC in combination with Kd (DKd)

Carfilzomib 70 mg/m^2 DRUG

Carfilzomib 70 mg/m\^2 will be administered IV.

Arm A: Carfilzomib+Dexamethasone (Kd); Arm B: Dara-SC in combination with Kd (DKd)

Dexamethasone 40 mg DRUG

Dexamethasone 40 mg will be administered as IV infusion or orally.

Arm A: Carfilzomib+Dexamethasone (Kd); Arm B: Dara-SC in combination with Kd (DKd)

Dara-SC 1800 mg DRUG

Dara-SC 1800 mg will be administered by SC injection.

Arm B: Dara-SC in combination with Kd (DKd)

Dexamethasone 20 mg DRUG

Dexamethasone 20 mg will be administered as IV infusion or orally.

Arm A: Carfilzomib+Dexamethasone (Kd); Arm B: Dara-SC in combination with Kd (DKd)

Eligibility Criteria

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

You may qualify if:

• Evidence of a response (partial response or better based on investigator's determination of response by International Myeloma Working Group \[IMWG\] criteria) to daratumumab-containing therapy with response duration of at least 4 months
• Participants must have progressed from or be refractory to their last line of treatment. Relapsed or refractory disease as defined as: a) Relapsed disease is defined as an initial response to previous treatment, followed by confirmed progressive disease (PD) by IMWG criteria greater than (\>) 60 days after cessation of treatment. b) Refractory disease is defined as less than (\<) 25 percent (%) reduction in M-protein or confirmed PD by IMWG criteria during previous treatment or \>60 days after cessation of treatment
• Received 1 to 3 prior line(s) of treatment of which one contained daratumumab, and completed daratumumab at least 3 months prior to randomization. A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram per day \[mg/day\] for 4 days) would not be considered prior lines of therapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2
• Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization

You may not qualify if:

• Previous treatment with daratumumab within the last 3 months prior to randomization
• Discontinuation of daratumumab due to a daratumumab-related adverse event (AE)
• History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
• Allergies, hypersensitivity, or intolerance to daratumumab, hyaluronidase, monoclonal antibodies (mAbs), human proteins, or their excipients, or known sensitivity to mammalian-derived products. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
• Participant is: a) Known to be seropositive for human immunodeficiency virus (HIV) with one or more of the following: not receiving highly active antiretroviral therapy (ART), had a change in ART within 6 months of the start of screening, receiving ART that may interfere with study treatment, cluster of differentiation (CD)4 count \<350 (unit: cells per cubic millimeter of blood) at screening, acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of start of screening, and not agreeing to start ART and be on ART \>4 weeks plus having HIV viral load \<400 copies/milliliters (mL) at end of 4-week period (to ensure ART is tolerated and HIV controlled. b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Participants with resolved infection (example: participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. c) Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (108)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Oncology Institute of Hope and Innovation

Tucson, Arizona, 85745, United States

Location

American Institute of Research (AIR)

Whittier, California, 90603, United States

Location

Fort Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, 46804, United States

Location

Karmanos Cancer Institute - Wayne State University

Detroit, Michigan, 48201, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University School Of Medicine

St Louis, Missouri, 63110-1032, United States

Location

Weill Medical College of Cornell University

New York, New York, 10065, United States

Location

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195, United States

Location

Baylor Scott and White Health

Dallas, Texas, 75246, United States

Location

Millennium Oncology

Houston, Texas, 77090, United States

Location

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Universidade Estadual De Campinas

Campinas, 13083-878, Brazil

Location

Liga Paranaense de Combate ao Cancer

Curitiba, 81520 060, Brazil

Location

Universidade Federal de Goias - Hospital das Clinicas da UFG

Goiânia, 74605-020, Brazil

Location

Liga Norte Riograndense Contra O Cancer

Natal, 59062 000, Brazil

Location

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, 90050-170, Brazil

Location

Ministerio da Saude Instituto Nacional do Cancer

Rio de Janeiro, 20230-130, Brazil

Location

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

Rio de Janeiro, 22775 001, Brazil

Location

Hospital Sao Rafael

Salvador, 41253-190, Brazil

Location

CEHON

Salvador, 45995-000, Brazil

Location

Instituto de Ensino e Pesquisa São Lucas

São Paulo, 01236-030, Brazil

Location

Real e Benemerita Associacao Portuguesa de Beneficencia

São Paulo, 01321-001, Brazil

Location

Clinica Sao Germano

São Paulo, 01455 010, Brazil

Location

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, 01509 900, Brazil

Location

Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncologia

São Paulo, 03102-002, Brazil

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Aarhus University Hospital

Aarhus N, DK-8200, Denmark

Location

Regionshospitalet i Holstebro

Holstebro, 7500, Denmark

Location

Haematological Research unit HFE-X OUH.

Odense, 5000, Denmark

Location

Vejle Hospital

Vejle, DK-7100, Denmark

Location

Hopital Claude Huriez

Lille, 59037, France

Location

CHU de Montpellier Hopital Saint Eloi

Montpellier, 34295, France

Location

Centre Hospitalier Emile Muller

Mulhouse, 68100, France

Location

Hotel Dieu

Nantes, 44035, France

Location

Hopitaux Universitaires Est Parisien Hopital Saint Antoine

Paris, 75012, France

Location

Hopital de la Pitie Salpetriere

Paris, 75013, France

Location

Hôpital Necker-Enfants Malades

Paris, 75743, France

Location

Fentre F Magendie, Hôpital Haut Leveque, CHU Bordeaux

Pessac, 33600, France

Location

Centre Hospitalier Lyon-Sud Service d'hematologie

Pierre-Bénite, 69310, France

Location

CHU Poitiers - Hopital la Miletrie

Poitiers, 86021, France

Location

Chu Rennes Hopital Pontchaillou

Rennes, 35033, France

Location

Institut Claudius Regaud

Toulouse, 31052, France

Location

CHU Bretonneau

Tours, 37044, France

Location

CHU Nancy Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Universitaetsklinikum Koelnt

Cologne, 50397, Germany

Location

Universitätsklinik Carl Gustav Carus, Med. Klinik u. Poliklinik I

Dresden, 1307, Germany

Location

Evangelisches Krankenhaus Essen-Werden

Essen, 45239, Germany

Location

Universitatsklinikum Essen

Essen, D-45147, Germany

Location

Universitatsklinik Hamburg Eppendorf UKE

Hamburg, 20246, Germany

Location

St. Barbara-Klinik Hamm GmbH

Hamm, 59075, Germany

Location

Praxisklinik für Haematologie und Onkologie Koblenz

Koblenz, 56068, Germany

Location

Universitätsmedizin der Johannes gutenberg-Universität; III. Med. Klinik - Germany

Mainz, 55101, Germany

Location

Onkologische Schwerpunkt Praxis

Saarbrücken, Germany

Location

Klinikum der Eberhard Karls Universitaet Abt fur innere Med II Haematologie Onkologie Germany

Tübingen, 72076, Germany

Location

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, 78052, Germany

Location

Universitätsklinikum Würzburg Med. Klinik U. Poliklinik Ii

Würzburg, 97080, Germany

Location

University of Athens - Evaggelismos Hospital (Evangelismos Hospital)

Athens, 106 76, Greece

Location

Alexandra General Hospital of Athens

Athens Attica, 115 28, Greece

Location

University Hospital Of Larissa

Larissa, 41110, Greece

Location

University General Hospital of Rio

Pátrai, 26500, Greece

Location

Anticancer Hospital of Thessaloniki Theageneio

Thessaloniki, 546 39, Greece

Location

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, 50139, Italy

Location

IRCCS Azienda Ospedaliera San Martino - IST

Genova, 16132, Italy

Location

San Martino Hospital

Genova, 16132, Italy

Location

Asst Ovest Milanese - Ospedale Di Legnano

Legnano, 20025, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Ospedale Maggiore della Carita

Novara, 28100, Italy

Location

Casa di Cura La Maddalena

Palermo, 90146, Italy

Location

Ospedale Villa Sofia-Cervello

Palermo, 90146, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Universita Degli Studi di Roma Tor Vergata

Roma, 00133, Italy

Location

Sapienza University of Rome

Roma, 00161, Italy

Location

Fondazione Policlinico Universitario A Gemelli IRCCS

Roma, 00168, Italy

Location

ASL ROMA

Roma, 30 - 00153, Italy

Location

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, 71013, Italy

Location

Azienda Ospedaliera Santa Maria

Terni, 5100, Italy

Location

Albert Schweitzer ziekenhuis-lokatie Dordwijk

Dordrecht, 3318 AT, Netherlands

Location

Zuyderland Medical Center

Sittard, 6130 MB, Netherlands

Location

Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy

Bydgoszcz, 85-168, Poland

Location

Szpital Wojewodzki w Opolu

Opole, 45-061, Poland

Location

Szpital Magodent

Warsaw, 01 748, Poland

Location

Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, 50 367, Poland

Location

Emergency Hospital of Dzerzhinsk

Dzerzhinsk, 606019, Russia

Location

S.P. Botkin Moscow City Clinical Hospital

Moscow, 125284, Russia

Location

Nizhniy Novgorod Region Clinical Hospital

Nizhny Novgorod, 603126, Russia

Location

Ryazan Regional Clinical Hospital

Ryazan, 390003, Russia

Location

Clinical Research Institute of Hematology and Transfusiology

Saint Petersburg, 191024, Russia

Location

Oncological dispensary #2

Sochi, 354057, Russia

Location

Oncology Dispensary of Komi Republic

Syktyvkar, 167904, Russia

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Inst. Cat. Doncologia-H Duran I Reynals

Barcelona, 08908, Spain

Location

Hosp. de Jerez de La Frontera

Jerez de la Frontera, 11407, Spain

Location

Hosp. de Leon

León, 24008, Spain

Location

Hosp. Univ. Ramon Y Cajal

Madrid, 28034, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Univ. de La Paz

Madrid, 28046, Spain

Location

Hosp. Costa Del Sol

Málaga, 29603, Spain

Location

Hosp. Univ. Son Espases

Palma, 7120, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Hosp. Univ. de Canarias

San Cristóbal de La Laguna, 38320, Spain

Location

Hosp. Virgen Del Rocio

Seville, 41013, Spain

Location

Hosp. Gral. Univ. de Toledo

Toledo, 45007, Spain

Location

Related Publications (1)

• Bahlis NJ, Zonder J, Karlin L, Plesner T, Paris L, Wrobel T, Hungria V, Besemer B, Crusoe E, Silkjaer T, Perrot A, Moreau P, Wu KL, Delimpasi S, Dimopoulos MA, Levin MD, Mangiacavalli S, Nnane I, Kim YJ, Krevvata M, Sha L, Wroblewski S, Tuozzo A, Carson R, Facon T. Subcutaneous daratumumab plus carfilzomib and dexamethasone (D-Kd) versus carfilzomib and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma who received previous daratumumab treatment: LYNX study. Leuk Lymphoma. 2025 Dec;66(14):2685-2696. doi: 10.1080/10428194.2025.2561117. Epub 2025 Oct 3.

  PMID: 41041907 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Global Medical Head
• 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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 12, 2019
• Study Start: May 31, 2019
• Primary Completion: October 24, 2022
• Study Completion: January 10, 2023
• Last Updated: March 30, 2025
• Results First Posted: December 19, 2023

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

US (11); ES (14); CA (1); BR (14); IT (18); NL (2); FR (14); BE (2); GR (5); DE (12); PL (4); DK (4); RU (7)