Multiple MyelomaPhase 2NCT03871829
Daratumumab Retreatment in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab
A Phase 2 study testing Carfilzomib 20 mg/m^2, Carfilzomib 70 mg/m^2 and Dexamethasone 40 mg in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 108 sites in 13 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Carfilzomib 20 mg/m^2, Carfilzomib 70 mg/m^2 and Dexamethasone 40 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 108 sitesin 13 countries
- Study dates
- 31 May 2019to 10 Jan 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
108 sites in 13 countries.
108 sites in 13 countries
Italy18 sites
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, 24127
Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi
Bologna, 40138
Azienda Ospedaliera Universitaria Careggi
Florence, 50139
IRCCS Azienda Ospedaliera San Martino - IST
Genova, 16132
San Martino Hospital
Genova, 16132
Asst Ovest Milanese - Ospedale Di Legnano
Legnano, 20025
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, 47014
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162
Ospedale Maggiore della Carita
Novara, 28100
Casa di Cura La Maddalena
Palermo, 90146
Ospedale Villa Sofia-Cervello
Palermo, 90146
Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
Universita Degli Studi di Roma Tor Vergata
Roma, 00133
Sapienza University of Rome
Roma, 00161
Fondazione Policlinico Universitario A Gemelli IRCCS
Roma, 00168
ASL ROMA
Roma, 30 - 00153
IRCCS Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, 71013
Azienda Ospedaliera Santa Maria
Terni, 5100
Brazil14 sites
Universidade Estadual De Campinas
Campinas, 13083-878
Liga Paranaense de Combate ao Cancer
Curitiba, 81520 060
Universidade Federal de Goias - Hospital das Clinicas da UFG
Goiânia, 74605-020
Liga Norte Riograndense Contra O Cancer
Natal, 59062 000
Irmandade Santa Casa de Misericordia de Porto Alegre
Porto Alegre, 90050-170
Ministerio da Saude Instituto Nacional do Cancer
Rio de Janeiro, 20230-130
Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
Rio de Janeiro, 22775 001
Hospital Sao Rafael
Salvador, 41253-190
CEHON
Salvador, 45995-000
Instituto de Ensino e Pesquisa São Lucas
São Paulo, 01236-030
Real e Benemerita Associacao Portuguesa de Beneficencia
São Paulo, 01321-001
Clinica Sao Germano
São Paulo, 01455 010
Fundacao Antonio Prudente A C Camargo Cancer Center
São Paulo, 01509 900
Instituto Brasileiro de Controle do Cancer - Sao Camilo Oncologia
São Paulo, 03102-002
France14 sites
Hopital Claude Huriez
Lille, 59037
CHU de Montpellier Hopital Saint Eloi
Montpellier, 34295
Centre Hospitalier Emile Muller
Mulhouse, 68100
Hotel Dieu
Nantes, 44035
Hopitaux Universitaires Est Parisien Hopital Saint Antoine
Paris, 75012
Hopital de la Pitie Salpetriere
Paris, 75013
Hôpital Necker-Enfants Malades
Paris, 75743
Fentre F Magendie, Hôpital Haut Leveque, CHU Bordeaux
Pessac, 33600
Centre Hospitalier Lyon-Sud Service d'hematologie
Pierre-Bénite, 69310
CHU Poitiers - Hopital la Miletrie
Poitiers, 86021
Chu Rennes Hopital Pontchaillou
Rennes, 35033
Institut Claudius Regaud
Toulouse, 31052
CHU Bretonneau
Tours, 37044
CHU Nancy Brabois
Vandœuvre-lès-Nancy, 54511
Spain14 sites
Hosp Clinic de Barcelona
Barcelona, 08036
Inst. Cat. Doncologia-H Duran I Reynals
Barcelona, 08908
Hosp. de Jerez de La Frontera
Jerez de la Frontera, 11407
Hosp. de Leon
León, 24008
Hosp. Univ. Ramon Y Cajal
Madrid, 28034
Hosp. Univ. 12 de Octubre
Madrid, 28041
Hosp. Univ. de La Paz
Madrid, 28046
Hosp. Costa Del Sol
Málaga, 29603
Hosp. Univ. Son Espases
Palma, 7120
Clinica Univ. de Navarra
Pamplona, 31008
Hosp Clinico Univ de Salamanca
Salamanca, 37007
Hosp. Univ. de Canarias
San Cristóbal de La Laguna, 38320
Hosp. Virgen Del Rocio
Seville, 41013
Hosp. Gral. Univ. de Toledo
Toledo, 45007
Germany12 sites
Universitaetsklinikum Koelnt
Cologne, 50397
Universitätsklinik Carl Gustav Carus, Med. Klinik u. Poliklinik I
Dresden, 1307
Evangelisches Krankenhaus Essen-Werden
Essen, 45239
Universitatsklinikum Essen
Essen, D-45147
Universitatsklinik Hamburg Eppendorf UKE
Hamburg, 20246
St. Barbara-Klinik Hamm GmbH
Hamm, 59075
Praxisklinik für Haematologie und Onkologie Koblenz
Koblenz, 56068
Universitätsmedizin der Johannes gutenberg-Universität; III. Med. Klinik - Germany
Mainz, 55101
Onkologische Schwerpunkt Praxis
Saarbrücken
Klinikum der Eberhard Karls Universitaet Abt fur innere Med II Haematologie Onkologie Germany
Tübingen, 72076
Schwarzwald-Baar Klinikum
Villingen-Schwenningen, 78052
Universitätsklinikum Würzburg Med. Klinik U. Poliklinik Ii
Würzburg, 97080
United States11 sites
Cleveland Clinic Main Campus
Cleveland, Ohio, 44195
Baylor Scott and White Health
Dallas, Texas, 75246
Karmanos Cancer Institute - Wayne State University
Detroit, Michigan, 48201
Fort Wayne Medical Oncology and Hematology, Inc.
Fort Wayne, Indiana, 46804
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Millennium Oncology
Houston, Texas, 77090
Weill Medical College of Cornell University
New York, New York, 10065
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
Washington University School Of Medicine
St Louis, Missouri, 63110-1032
Oncology Institute of Hope and Innovation
Tucson, Arizona, 85745
American Institute of Research (AIR)
Whittier, California, 90603
Russia7 sites
Emergency Hospital of Dzerzhinsk
Dzerzhinsk, 606019
S.P. Botkin Moscow City Clinical Hospital
Moscow, 125284
Nizhniy Novgorod Region Clinical Hospital
Nizhny Novgorod, 603126
Ryazan Regional Clinical Hospital
Ryazan, 390003
Clinical Research Institute of Hematology and Transfusiology
Saint Petersburg, 191024
Oncological dispensary #2
Sochi, 354057
Oncology Dispensary of Komi Republic
Syktyvkar, 167904
Greece5 sites
University of Athens - Evaggelismos Hospital (Evangelismos Hospital)
Athens, 106 76
Alexandra General Hospital of Athens
Athens Attica, 115 28
University Hospital Of Larissa
Larissa, 41110
University General Hospital of Rio
Pátrai, 26500
Anticancer Hospital of Thessaloniki Theageneio
Thessaloniki, 546 39
Denmark4 sites
Aarhus University Hospital
Aarhus N, DK-8200
Regionshospitalet i Holstebro
Holstebro, 7500
Haematological Research unit HFE-X OUH.
Odense, 5000
Vejle Hospital
Vejle, DK-7100
Poland4 sites
Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy
Bydgoszcz, 85-168
Szpital Wojewodzki w Opolu
Opole, 45-061
Szpital Magodent
Warsaw, 01 748
Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu
Wroclaw, 50 367
Netherlands2 sites
Albert Schweitzer ziekenhuis-lokatie Dordwijk
Dordrecht, 3318 AT
Zuyderland Medical Center
Sittard, 6130 MB
About this study
Official title: A Phase 2 Study of Daratumumab Subcutaneous (Dara-SC) Administration in Combination With Carfilzomib and Dexamethasone (DKd) Compared With Carfilzomib and Dexamethasone (Kd) in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab to Evaluate Daratumumab Retreatment
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.
Read the 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
- Being tested
- Carfilzomib 20 mg/m^2, Carfilzomib 70 mg/m^2, Dexamethasone 40 mg, Dara-SC 1800 mg, Dexamethasone 20 mg
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carfilzomib 20 mg/m^2Drug
Carfilzomib 20 mg/m^2 will be administered intravenously (IV).
Carfilzomib 70 mg/m^2Drug
Carfilzomib 70 mg/m^2 will be administered IV.
Dexamethasone 40 mgDrug
Dexamethasone 40 mg will be administered as IV infusion or orally.
Dara-SC 1800 mgDrug
Dara-SC 1800 mg will be administered by SC injection.
Dexamethasone 20 mgDrug
Dexamethasone 20 mg will be administered as IV infusion or orally.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 3 years and 4 months
Secondary outcomes (9)
Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved partial response (PR) or better responses based on the computerized algorithm, in accordance with the IMWG criteria, during or after the study treatment but before the start of subsequent anti-myeloma therapy. IMWG criteria for PR: greater than or equal to (>=)50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or less than (<)200 mg/24 hours; If the serum and urine M-protein were not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels was required in place of the M-protein criteria; If serum and urine M-protein were not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) was required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%; additionally, if present at baseline, >=50% reduction in the size of soft tissue PCs was also required.
Measured: Up to 3 years and 7 months
Percentage of Participants Achieving Complete Response (CR) or Better
Percentage of participants achieving CR or better were reported. CR or better rate was defined as the percentage of participants achieving CR or sCR based on the computerized algorithm, according to IMWG response criteria. IMWG criteria for CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas (PCs), and <5% PCs in bone marrow.
Measured: Up to 3 years and 7 months
Progression Free Survival (PFS)
PFS was defined as the duration from the date of randomization to either progressive disease (PD) or death, whichever comes first. IMWG criteria for PD: >=25% from lowest response level in serum M-component (the absolute increase must be >=0.5 gram per deciliter [g/dL]) and/or in urine M-component (the absolute increase must be >=200 mg/24 hour); only in participants without measurable serum and urine M-protein levels: increase of >=25% in the difference between involved and uninvolved free light chain levels and the absolute increase must be >10 mg/dL. BMPC%: the absolute % must be >=10%; definite increase in size of existing bone lesions or soft tissue plasmacytomas; definite development of new bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 milligrams per deciliter (mg/dL) or 2.65 millimoles per liter [mmol/L]) that can be attributed solely to PC proliferative disorder.
Measured: Up to 3 years and 7 months
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.
Measured: Up to 3 years and 7 months
Percentage of Participants With Negative Minimal Residual Disease (MRD)
Percentage of participants with negative MRD were reported. MRD negativity rate, defined as the percentage of participants who had MRD negative status at 10^-5 by bone marrow aspirate after the date of randomization and prior to PD or subsequent anti-myeloma therapy.
Measured: Up to 3 years and 7 months
Time to Next Treatment
Time to next treatment was defined as the time from randomization to the start of the next-line treatment.
Measured: Up to 3 years and 7 months
Serum Concentrations of Daratumumab
Serum concentrations of daratumumab were assessed. This outcome measure was planned to be analyzed for specified arm only.
Measured: Day 1 of Cycles 1, 3, and 7 (each cycle of 28 days) and Follow Up (post treatment Week 8; up to 30.3 months)
Number of Participants With Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies
The incidence of anti-rHuPH20 antibodies were summarized for all participants who received at least one dose of Dara-SC and had appropriate plasma samples for detection of antibodies to rHuPH20 (at least 1 sample after the start of the first dose of Dara-SC). This outcome measure was planned to be analyzed for specified arm only.
Measured: Up to end of study; up to 30.3 months
Number of Participants With Anti-Daratumumab Antibodies
Number of participants who test positive for anti-daratumumab antibodies were reported. This outcome measure was planned to be analyzed for specified arm only.
Measured: Up to end of study; up to 30.3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2019
- Study start31 May 2019
- Primary completion24 Oct 2022
- Study completion10 Jan 2023
Why it stopped: The decision was made to discontinue the 54767414MMY2065 study as the Data Review Committee recommendation was early stop of the study for futility.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03871829
- Sponsor's protocol ID
- CR108598
- Other IDs
- 2018-004185-34, 54767414MMY2065, 2018
- Status last verified
- Mar 2025
- First submitted
- 11 Mar 2019
- Last updated
- 30 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
Publications
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.
PubMed 41041907
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Daratumumab Subcutaneous (Dara-SC) Administration in Combination With Carfilzomib and Dexamethasone (DKd) Compared With Carfilzomib and Dexamethasone (Kd) in Participants With Multiple Myeloma Who Have Been Previously Treated With Daratumumab to Evaluate Daratumumab Retreatment
- ClinicalTrials.gov ID
- NCT03871829
- Acronym / sponsor ID
- CR108598
- Conditions
- Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The decision was made to discontinue the 54767414MMY2065 study as the Data Review Committee recommendation was early stop of the study for futility.
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 31 May 2019 (actual)
- Primary completion
- 24 Oct 2022 (actual)
- Study completion
- 10 Jan 2023 (actual)
- First posted
- 12 Mar 2019 (actual)
- Results
- Posted 19 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Carfilzomib+Dexamethasone (Kd) | Active comparator | Drug: Carfilzomib 20 mg/m^2, Drug: Carfilzomib 70 mg/m^2, Drug: Dexamethasone 40 mg, Drug: Dexamethasone 20 mgParticipants 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. |
| Arm B: Dara-SC in combination with Kd (DKd) | Experimental | Drug: Carfilzomib 20 mg/m^2, Drug: Carfilzomib 70 mg/m^2, Drug: Dexamethasone 40 mg, Drug: Dara-SC 1800 mg, Drug: Dexamethasone 20 mgParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carfilzomib 20 mg/m^2Carfilzomib 20 mg/m^2 will be administered intravenously (IV). | Drug | Arm A: Carfilzomib+Dexamethasone (Kd), Arm B: Dara-SC in combination with Kd (DKd) |
| Carfilzomib 70 mg/m^2Carfilzomib 70 mg/m^2 will be administered IV. | Drug | Arm A: Carfilzomib+Dexamethasone (Kd), Arm B: Dara-SC in combination with Kd (DKd) |
| Dexamethasone 40 mgDexamethasone 40 mg will be administered as IV infusion or orally. | Drug | Arm A: Carfilzomib+Dexamethasone (Kd), Arm B: Dara-SC in combination with Kd (DKd) |
| Dara-SC 1800 mgDara-SC 1800 mg will be administered by SC injection. | Drug | Arm B: Dara-SC in combination with Kd (DKd) |
| Dexamethasone 20 mgDexamethasone 20 mg will be administered as IV infusion or orally. | Drug | Arm A: Carfilzomib+Dexamethasone (Kd), Arm B: Dara-SC in combination with Kd (DKd) |
Primary outcome
Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response
Time frame: Up to 3 years and 4 months
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.
9 secondary outcomes
Overall Response Rate (ORR)
Time frame: Up to 3 years and 7 months
Percentage of Participants Achieving Complete Response (CR) or Better
Time frame: Up to 3 years and 7 months
Progression Free Survival (PFS)
Time frame: Up to 3 years and 7 months
Overall Survival (OS)
Time frame: Up to 3 years and 7 months
Percentage of Participants With Negative Minimal Residual Disease (MRD)
Time frame: Up to 3 years and 7 months
Time to Next Treatment
Time frame: Up to 3 years and 7 months
Serum Concentrations of Daratumumab
Time frame: Day 1 of Cycles 1, 3, and 7 (each cycle of 28 days) and Follow Up (post treatment Week 8; up to 30.3 months)
Number of Participants With Anti-recombinant Human Hyaluronidase (rHuPH20) Antibodies
Time frame: Up to end of study; up to 30.3 months
Number of Participants With Anti-Daratumumab Antibodies
Time frame: Up to end of study; up to 30.3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41041907Bahlis 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.
- Individual participant dataSharing planned: Yes. The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
108 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carfilzomib 20 mg/m^2, Carfilzomib 70 mg/m^2 and Dexamethasone 40 mg in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 108 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 108 sites in Italy, Brazil, France, Spain, Germany and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving Very Good Partial Response (VGPR) or Better Response (time frame: Up to 3 years and 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03871829, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.