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

NCT ID: NCT03871829

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-31
• Study Completion Date: 2023-01-10

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.

Detailed Description

For relapsed or refractory multiple myeloma, the treatment is determined on an individual basis. Common standard of care regimens use either a proteasome inhibitor (PI) or an immunomodulatory agent (IMiD) in combination with dexamethasone with or without a monoclonal antibody (mAb) such as daratumumab. After relapse from PIs or IMiDs, patients are often retreated with drugs that have same mechanism of action to which they have been sensitive. The disease becomes refractory and all effective treatment options are exhausted. Daratumumab is a human IgG1 mAb that binds with high affinity to unique epitope on cluster of differentiation 38 (CD38) and attacks tumor cells that overexpress CD38. Study is to determine the efficacy of Dara-SC in combination with carfilzomib and dexamethasone (DKd) in adult participants with relapsed refractory MM who had 1 to 3 prior line(s) of treatment including a line containing daratumumab to evaluate daratumumab retreatment. The MM treatment is determined on an individual basis where patient's age, prior therapy, bone marrow function, co-morbidities, patient preference and time to relapse are considered. Common standard of care regimens use either PI or an IMiD in combination with dexamethasone with or without a mAb. It is a targeted immunotherapy that attacks tumor cells that overexpress CD38, a transmembrane glycoprotein, in a variety of hematological malignancies including multiple myeloma. The study will be conducted in 3 phases: Screening (28 days), Treatment, and Follow-Up. Assessments like chest X-ray, spirometry test, electrocardiogram (ECG), will be performed during Screening phase. During the Treatment Phase, participants will be randomized to receive Kd or DKd. Efficacy assessments like bone marrow examination will be performed. Follow-up will continue until the end of study.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Carfilzomib+Dexamethasone (Kd)

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.

Group Type: ACTIVE_COMPARATOR

Carfilzomib 20 mg/m^2

Intervention Type: DRUG

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

Carfilzomib 70 mg/m^2

Intervention Type: DRUG

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

Dexamethasone 40 mg

Intervention Type: DRUG

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

Dexamethasone 20 mg

Intervention Type: DRUG

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

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

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.

Group Type: EXPERIMENTAL

Carfilzomib 20 mg/m^2

Intervention Type: DRUG

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

Carfilzomib 70 mg/m^2

Intervention Type: DRUG

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

Dexamethasone 40 mg

Intervention Type: DRUG

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

Dara-SC 1800 mg

Intervention Type: DRUG

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

Dexamethasone 20 mg

Intervention Type: DRUG

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

Interventions

Carfilzomib 20 mg/m^2

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

Intervention Type: DRUG

Carfilzomib 70 mg/m^2

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

Intervention Type: DRUG

Dexamethasone 40 mg

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

Intervention Type: DRUG

Dara-SC 1800 mg

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

Intervention Type: DRUG

Dexamethasone 20 mg

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Oncology Institute of Hope and Innovation

Tucson, Arizona, United States

American Institute of Research (AIR)

Whittier, California, United States

Fort Wayne Medical Oncology and Hematology, Inc.

Fort Wayne, Indiana, United States

Karmanos Cancer Institute - Wayne State University

Detroit, Michigan, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Washington University School Of Medicine

St Louis, Missouri, United States

Weill Medical College of Cornell University

New York, New York, United States

Cleveland Clinic Main Campus

Cleveland, Ohio, United States

Baylor Scott and White Health

Dallas, Texas, United States

Millennium Oncology

Houston, Texas, United States

ZNA Stuivenberg

Antwerp, , Belgium

UZ Gent

Ghent, , Belgium

Universidade Estadual De Campinas

Campinas, , Brazil

Liga Paranaense de Combate ao Cancer

Curitiba, , Brazil

Universidade Federal de Goias - Hospital das Clinicas da UFG

Goiânia, , Brazil

Liga Norte Riograndense Contra O Cancer

Natal, , Brazil

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, , Brazil

Ministerio da Saude Instituto Nacional do Cancer

Rio de Janeiro, , Brazil

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

Rio de Janeiro, , Brazil

Hospital Sao Rafael

Salvador, , Brazil

CEHON

Salvador, , Brazil

Instituto de Ensino e Pesquisa São Lucas

São Paulo, , Brazil

Real e Benemerita Associacao Portuguesa de Beneficencia

São Paulo, , Brazil

Clinica Sao Germano

São Paulo, , Brazil

Fundacao Antonio Prudente A C Camargo Cancer Center

São Paulo, , Brazil

Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncologia

São Paulo, , Brazil

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Aarhus University Hospital

Aarhus N, , Denmark

Regionshospitalet i Holstebro

Holstebro, , Denmark

Haematological Research unit HFE-X OUH.

Odense, , Denmark

Vejle Hospital

Vejle, , Denmark

Hopital Claude Huriez

Lille, , France

CHU de Montpellier Hopital Saint Eloi

Montpellier, , France

Centre Hospitalier Emile Muller

Mulhouse, , France

Hotel Dieu

Nantes, , France

Hopitaux Universitaires Est Parisien Hopital Saint Antoine

Paris, , France

Hopital de la Pitie Salpetriere

Paris, , France

Hôpital Necker-Enfants Malades

Paris, , France

Fentre F Magendie, Hôpital Haut Leveque, CHU Bordeaux

Pessac, , France

Centre Hospitalier Lyon-Sud Service d'hematologie

Pierre-Bénite, , France

CHU Poitiers - Hopital la Miletrie

Poitiers, , France

Chu Rennes Hopital Pontchaillou

Rennes, , France

Institut Claudius Regaud

Toulouse, , France

CHU Bretonneau

Tours, , France

CHU Nancy Brabois

Vandœuvre-lès-Nancy, , France

Universitaetsklinikum Koelnt

Cologne, , Germany

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

Dresden, , Germany

Evangelisches Krankenhaus Essen-Werden

Essen, , Germany

Universitatsklinikum Essen

Essen, , Germany

Universitatsklinik Hamburg Eppendorf UKE

Hamburg, , Germany

St. Barbara-Klinik Hamm GmbH

Hamm, , Germany

Praxisklinik für Haematologie und Onkologie Koblenz

Koblenz, , Germany

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

Mainz, , Germany

Onkologische Schwerpunkt Praxis

Saarbrücken, , Germany

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

Tübingen, , Germany

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, , Germany

Universitätsklinikum Würzburg Med. Klinik U. Poliklinik Ii

Würzburg, , Germany

University of Athens - Evaggelismos Hospital (Evangelismos Hospital)

Athens, , Greece

Alexandra General Hospital of Athens

Athens Attica, , Greece

University Hospital Of Larissa

Larissa, , Greece

University General Hospital of Rio

Pátrai, , Greece

Anticancer Hospital of Thessaloniki Theageneio

Thessaloniki, , Greece

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, , Italy

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

Bologna, , Italy

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

IRCCS Azienda Ospedaliera San Martino - IST

Genova, , Italy

San Martino Hospital

Genova, , Italy

Asst Ovest Milanese - Ospedale Di Legnano

Legnano, , Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Ospedale Maggiore della Carita

Novara, , Italy

Casa di Cura La Maddalena

Palermo, , Italy

Ospedale Villa Sofia-Cervello

Palermo, , Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Universita Degli Studi di Roma Tor Vergata

Roma, , Italy

Sapienza University of Rome

Roma, , Italy

Fondazione Policlinico Universitario A Gemelli IRCCS

Roma, , Italy

ASL ROMA

Roma, , Italy

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, , Italy

Azienda Ospedaliera Santa Maria

Terni, , Italy

Albert Schweitzer ziekenhuis-lokatie Dordwijk

Dordrecht, , Netherlands

Zuyderland Medical Center

Sittard, , Netherlands

Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy

Bydgoszcz, , Poland

Szpital Wojewodzki w Opolu

Opole, , Poland

Szpital Magodent

Warsaw, , Poland

Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, , Poland

Emergency Hospital of Dzerzhinsk

Dzerzhinsk, , Russia

S.P. Botkin Moscow City Clinical Hospital

Moscow, , Russia

Nizhniy Novgorod Region Clinical Hospital

Nizhny Novgorod, , Russia

Ryazan Regional Clinical Hospital

Ryazan, , Russia

Clinical Research Institute of Hematology and Transfusiology

Saint Petersburg, , Russia

Oncological dispensary #2

Sochi, , Russia

Oncology Dispensary of Komi Republic

Syktyvkar, , Russia

Hosp Clinic de Barcelona

Barcelona, , Spain

Inst. Cat. Doncologia-H Duran I Reynals

Barcelona, , Spain

Hosp. de Jerez de La Frontera

Jerez de la Frontera, , Spain

Hosp. de Leon

León, , Spain

Hosp. Univ. Ramon Y Cajal

Madrid, , Spain

Hosp. Univ. 12 de Octubre

Madrid, , Spain

Hosp. Univ. de La Paz

Madrid, , Spain

Hosp. Costa Del Sol

Málaga, , Spain

Hosp. Univ. Son Espases

Palma, , Spain

Clinica Univ. de Navarra

Pamplona, , Spain

Hosp Clinico Univ de Salamanca

Salamanca, , Spain

Hosp. Univ. de Canarias

San Cristóbal de La Laguna, , Spain

Hosp. Virgen Del Rocio

Seville, , Spain

Hosp. Gral. Univ. de Toledo

Toledo, , Spain

Countries

United States; Belgium; Brazil; Canada; Denmark; France; Germany; Greece; Italy; Netherlands; Poland; Russia; Spain

References

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 Oct 3:1-12. doi: 10.1080/10428194.2025.2561117. Online ahead of print.

Reference Type: DERIVED

PMID: 41041907 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-004185-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

54767414MMY2065

Identifier Type: OTHER

Identifier Source: secondary_id

CR108598

Identifier Type: -

Identifier Source: org_study_id