Multiple MyelomaPhase 2NCT03412565
A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens
A Phase 2 study testing Daratumumab, Bortezomib and Lenalidomide in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 64 sites in 9 countries.
Trial summary
The purpose of this study is to evaluate the clinical benefit of subcutaneous (SC) daratumumab administered in combination with standard multiple myeloma (MM) regimens in participants with MM as measured by overall response rate (ORR) or very good partial response (VGPR) or better rate. 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?
- Daratumumab, Bortezomib and Lenalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 265 participants
- Where
- 64 sitesin 9 countries
- Study dates
- 26 Apr 2018to 18 Apr 2024
- 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
- Multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG) diagnostic criteria
- Measurable, secretory disease as defined by any of the following:
- Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL); or
- Urine M-protein level >= 200 milligram per 24 hours (mg/24 hours); or
- Light chain multiple myeloma (MM), for participants without measurable disease in the serum or urine: serum Immunoglobulin (Ig) free light chain (FLC) >= 10 mg/dL and abnormal FLC ratio
- Meets one of the sets of the following criteria:
Show all 11Show fewer
- For Daratumumab + bortezomib + lenalidomide + dexamethasone (D-VRd) and Daratumumab + bortezomib + melphalan + prednisone + dexamethasone (D-VMP) regimen: newly diagnosed myeloma
- For Daratumumab + lenalidomide + dexamethasone (D-Rd) and Daratumumab + Carfilzomib + Dexamethasone (D-Kd) regimen: relapsed or refractory disease
- D-Kd cohort: Participants must have received only 1 prior line of therapy for MM which included at least 2 consecutive cycles of lenalidomide therapy
- Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0, 1, or 2
- During the study, during dose interruptions, and for 3 months after receiving the last dose of any component of the study treatment, a female participant must agree not to donate eggs (ova, oocytes) and male participants of reproductive potential must not donate semen or sperm during the study, during dose interruptions, or for 3 months after the last dose of any study drug
Who cannot join
- History of malignancy (other than MM) unless all treatment of that malignancy was completed at least 2 years before consent and the participant 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
- Exhibits clinical signs of meningeal involvement of MM
- Either of the following: a) Chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) is less than (<) 50 percentage (%) of predicted normal b) Moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification c) For D-Kd cohort: Known infiltrative pulmonary disease or known pulmonary hypertension
- Any of the following: a) Known to be seropositive for human immunodeficiency virus; b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (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) DNA levels. Those who are polymerase chain reaction (PCR) positive will be excluded
- Known to be seropositive for hepatitis C (Anti-HCV antibody positive or HCV-RNA quantitation positive) except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy
- For D-Kd cohort only: Transthoracic echocardiogram showing left ventricular ejection fraction (LVEF) <40%; uncontrolled hypertension, defined as an average systolic blood pressure greater than (>)159 millimeters of mercury (mmHg) or diastolic >99 mmHg despite optimal treatment
Trial locations and contacts
64 sites in 9 countries.
64 sites in 9 countries
United States16 sites
Billings Clinic
Billings, Montana, 59101
University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic
Charlottesville, Virginia, 22903
Karmonos Cancer Institute
Detroit, Michigan, 48201
San Juan Oncology Associates
Farmington, New Mexico, 87401
Mayo Clinic in Florida
Jacksonville, Florida, 32224
Nebraska Hematology and Oncology
Lincoln, Nebraska, 68506
Southeast Nebraska Cancer Center
Lincoln, Nebraska, 68510
NYU Winthrop
Mineola, New York, 11501
Mt. Sinai School of Medicine
New York, New York, 10029
Nebraska Cancer Specialists
Omaha, Nebraska, 68130
UF Health Cancer Center at Orlando Health
Orlando, Florida, 32806
Utah Cancer Specialists
Salt Lake City, Utah, 84121
Avera Medical Group - Oncology & Hematology
Sioux Falls, South Dakota, 57105
Providence Cancer Center
Southfield, Michigan, 48075
Cancer Center of Central Connecticut - Southington
Southington, Connecticut, 06489-3237
Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
Spain12 sites
Inst. Cat. D'Oncologia-Badalona
Badalona, 08916
Hosp Clinic de Barcelona
Barcelona, 08036
Inst. Cat. Doncologia-H Duran I Reynals
Barcelona, 08908
Hosp Univ Vall D Hebron
Barcelona, 8035
Hosp. Gral. Univ. Gregorio Maranon
Madrid, 28007
Clinica Univ. de Navarra
Madrid, 28027
Hosp. Univ. Ramon Y Cajal
Madrid, 28034
Hosp. Univ. 12 de Octubre
Madrid, 28041
Hosp. Son Llatzer
Mallorca, 07198
Clinica Univ. de Navarra
Pamplona, 31008
Hosp Clinico Univ de Salamanca
Salamanca, 37007
Hosp. Univ. Dr. Peset
Valencia, 46017
Brazil6 sites
Liga Norte Riograndense Contra O Cancer
Natal, 59062 000
Associacao Hospitalar Beneficente Sao Vicente de Paulo - Hospital Sao Vicente de Paulo
Passo Fundo, 99010-090
Ministerio da Saude Instituto Nacional do Cancer
Rio de Janeiro, 20230 130
Clinica Sao Germano
São Paulo, 01455 010
SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
São Paulo, 04037-002
Instituto de Assistencia Medica ao Servidor Publico Estadual IAMSPE
São Paulo, 04039-004
Israel6 sites
Rambam Medical Center
Haifa, 31096
Carmel Medical Center
Haifa, 3436212
Hadassah Medical Center
Jerusalem, 9112001
Galilee Medical Center
Nahariya, 22100
Sheba Medical Center
Ramat Gan, 52621
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
United Kingdom6 sites
Heart of England NHS Foundation Trust
Birmingham, B9 5SS
Royal Bournemouth Hospital
Bournemouth, BH7 7DW
Kent and Canterbury Hospital
Canterbury, CT1 3NG
Manchester Royal Infirmary
Manchester, M13 9WL
Derriford Hospital
Plymouth, PL6 8DH
Royal Stoke University Hospital
Stoke-on-Trent, ST4 6QG
France5 sites
CHU de Nantes hotel Dieu
Nantes, 44093
CHU de Bordeaux - Hospital Haut-Leveque
Pessac, 33604
Centre hospitalier Lyon-Sud
Pierre-Bénite, 69495
CHU Bretonneau
Tours, 37044
CHU Nancy Brabois
Vandœuvre-lès-Nancy, 54511
Germany5 sites
Klinikum Chemnitz gGmbH
Chemnitz, 09113
Universitaetsklinikum Hamburg Eppendorf
Hamburg, 20246
Asklepios Klinik Altona
Hamburg, 22763
Universitaetsklinikum Heidelberg
Heidelberg, 69120
Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,
Tübingen, 72076
Czechia4 sites
Fakultni nemocnice Brno
Brno, 625 00
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05
Fakultni Nemocnice Ostrava
Ostrava, 70852
Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
Prague, 128 08
Japan4 sites
Kanazawa University Hospital
Kanazawa, 920 8641
Matsuyama Red Cross Hospital
Matsuyama, 790-8524
Nagoya City University Hospital
Nagoya, 467 8602
Japanese Red Cross Medical Center
Shibuya City, 150-8935
About this study
Official title: A Multicenter Phase 2 Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens
The purpose of this study is to evaluate the clinical benefit of subcutaneous (SC) daratumumab administered in combination with standard multiple myeloma (MM) regimens in participants with MM as measured by overall response rate (ORR) or very good partial response (VGPR) or better rate.
Read the detailed description
The hypothesis is that the addition of daratumumab administered SC to standard MM regimens will improve responses compared to response data observed in completed phase 3 studies without daratumumab. Disease evaluations will include measurements of myeloma proteins, bone marrow examinations, skeletal surveys, assessment of extramedullary plasmacytomas, and measurements of serum calcium corrected for albumin. Safety will be measured by adverse events, laboratory test results, electrocardiogram (ECGs), vital sign measurements, physical examination findings, SC injection-site assessments, and assessment of Eastern Cooperative Oncology Group (ECOG) performance status score. Study will consist of 3 phases (screening, treatment and follow-up) and duration of study is approximately 3 years.
- Conditions
- Multiple Myeloma
- Being tested
- Daratumumab, Bortezomib, Lenalidomide, Dexamethasone, Melphalan
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaratumumabDrug
Daratumumab will be administered at a dose of 1800 mg by SC injection in Cycles 1 to 4 in D-VRd cohort and until documented progression of disease, unacceptable toxicity, or end of study for D-VMP, D-Rd and D-Kd cohorts.
BortezomibDrug
Bortezomib will be administered as 1.3 mg/m^2 SC injection in Cycles 1 to 4 in D-VRd cohort and in Cycles 1 to 9 in D-VMP cohort.
LenalidomideDrug
Lenalidomide will be administered as 25 mg capsule orally in Cycles 1 to 4 in D-VRd cohort and in all Cycles until documented progression of disease, unacceptable toxicity, or end of study in D-Rd cohort.
DexamethasoneDrug
Dexamethasone will be administered as 20 mg orally or intravenously in Cycles 1 to 4 in D-VRd cohort; 40 mg orally or intravenously in all cycles and thereafter until documented progression of disease, unacceptable toxicity, or end of study in D-Rd and D-Kd cohort.
MelphalanDrug
Melphalan will be administered as 9 mg/m^2 orally in Cycles 1 to 9.
PrednisoneDrug
Prednisone will be administered as 60 mg/m^2 orally in cycles 1 to 9.
CarfilzomibDrug
Carfilzomib will be administered as 20 mg/m^2 IV on Day 1 of Cycle 1 only then 70 mg/m^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or end of study in D-Kd cohort.
| Study group | Role | What they receive |
|---|---|---|
| Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) | Experimental | Participants will receive daratumumab 1800 milligram (mg) by subcutaneous (SC) injection on Days 1, 8 and 15 of Cycles 1 to 3 (each cycle of 21 days) and on Day 1 of Cycle 4; bortezomib 1.3 milligram per square meter (mg/m^2) SC injection on Days 1, 4, 8 and 11 of Cycles 1 to 4; lenalidomide 25 mg orally on Day 1 through Day 14 of Cycles 1 to 4 and dexamethasone 20 mg orally or intravenously on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4. Receives: Drug: Daratumumab; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone |
| D + Bortezomib + Melphalan + Prednisone (D-VMP) | Experimental | Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1 then on Days 1 and 22 in Cycles 2 to 9 and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; bortezomib 1.3 mg/m^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m^2 orally on Days 1 to 4 of cycles 1 to 9. Receives: Drug: Daratumumab; Drug: Bortezomib; Drug: Melphalan; Drug: Prednisone |
| Daratumumab + Lenalidomide + Dexamethasone (D-Rd) | Experimental | Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 then on Day 1 and 15 of Cycles 3 to 6 and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or end of study. Receives: Drug: Daratumumab; Drug: Lenalidomide; Drug: Dexamethasone |
| Daratumumab + Carfilzomib + Dexamethasone (D-Kd) | Experimental | Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days) then on Day 1 and 15 of Cycles 3 to 6 and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; Carfilzomib 20 mg/m^2 intravenously (IV) on Day 1 of Cycle 1 only then 70 mg/m^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or IV weekly for Cycles 1-9 then on Days 1, 8, 15 of each cycle for Cycles 10 and thereafter until documented progression of disease, unacceptable toxicity, or end of study. Receives: Drug: Daratumumab; Drug: Dexamethasone; Drug: Carfilzomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 milligrams (mg) per 24 hours, If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
Measured: Up to 2 years 3 months
D-VRd Cohort: Percentage of Participants With Very Good Partial Response (VGPR) or Better Response
VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response [sCR]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg/24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.
Measured: Up to 2 years and 3 months
Secondary outcomes (9)
Maximum Observed Serum Concentration (Cmax) of Daratumumab
Cmax was defined as maximum serum concentration observed following daratumumab administration. Each cycle for: D-VRd cohort is of 21 days, D-VMP cohort is of 42 days and D-Rd and D-Kd cohorts is of 28 days. Each cohort have a treatment period of 84 days.
Measured: D-VRd: Day 4 of Cycles 1 and 4 and post treatment at Week 8; D-VMP: Day 4 of Cycles 1 and 2 and post treatment at Week 8; D-Rd and D-Kd: Day 4 of Cycles 1 and 3 and post treatment at Week 8
Percentage of Participants With Infusion-Related Reactions (IRRs)
Percentage of Participants with IRRs were reported. The administration-related systemic reactions are referred to as IRRs.
Measured: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With VGPR or Better Response
VGPR or better rate was defined as the percentage of participants who achieved VGPR or CR (including sCR) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.
Measured: From baseline up to 2 years 7 months
D-VRd Cohort: Overall Response Rate (ORR)
ORR was defined as the percentage of participants who achieved a PR or better, IMWG criteria, during the study or during follow up. IMWG criteria for PR >= 50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by >=90% or to <200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
Measured: Up to 2 years and 3 months
Percentage of Participants With CR or Better Response
CR or better rate was defined as the percentage of participants with a CR or better response (that is, CR and sCR) as per IMWG criteria. CR: as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (<) 5 percent plasma cells in bone marrow; sCR: CR plus normal FLC ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry.
Measured: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months
D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)
DOR was defined as the time from the date of initial documented response (PR or better response) to the date of first documented evidence of progressive disease (PD) or death due to PD. PD is defined as an increase of 25% from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >=0.5 gram per deciliter [g/dL] and >=200 mg/24 hours respectively); only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dL); definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Measured: From baseline up to 2 years 7 months
Percentage of Participants With Anti-Daratumumab Antibodies
Percentage of participants with antibodies to daratumumab were reported.
Measured: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months
Percentage of Participants With Anti-rHuPH20 Antibodies
Percentage of participants with antibodies to rHuPH20 were reported.
Measured: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With Minimal Residual Disease (MRD) Negative Rate
MRD negativity rate was defined as the percentage of participants who were considered MRD negative after MRD testing at any timepoint after the first dose by bone marrow aspirate. MRD negativity rate was assessed by next-generation sequencing at a threshold of <10^5.
Measured: Up to 2 years and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2018
- Study start26 Apr 2018
- Primary completion12 Aug 2020
- Study completion18 Apr 2024
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 265 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
- NCT03412565
- Sponsor's protocol ID
- CR108435
- Other IDs
- 2017-004203-41, 54767414MMY2040, 2017
- Status last verified
- Apr 2025
- First submitted
- 22 Jan 2018
- Last updated
- 29 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Moreau P, Chari A, Oriol A, Martinez-Lopez J, Haenel M, Touzeau C, Ailawadhi S, Besemer B, de la Rubia Comos J, Encinas C, Mateos MV, Salwender H, Rodriguez-Otero P, Hulin C, Karlin L, Sureda Balari A, Bargay J, Benboubker L, Rosinol L, Tarantolo S, Terebelo H, Yang S, Wang J, Nnane I, Qi M, Kosh M, Delioukina M, Goldschmidt H. Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS. Blood Cancer J. 2023 Mar 7;13(1):33. doi: 10.1038/s41408-023-00805-x. No abstract available.
PubMed 36882409
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase 2 Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens
- ClinicalTrials.gov ID
- NCT03412565
- Acronym / sponsor ID
- CR108435
- Conditions
- Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 265 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 26 Apr 2018 (actual)
- Primary completion
- 12 Aug 2020 (actual)
- Study completion
- 18 Apr 2024 (actual)
- First posted
- 26 Jan 2018 (actual)
- Results
- Posted 12 Jan 2022
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 evaluate the clinical benefit of subcutaneous (SC) daratumumab administered in combination with standard multiple myeloma (MM) regimens in participants with MM as measured by overall response rate (ORR) or very good partial response (VGPR) or better rate.
Detailed description
The hypothesis is that the addition of daratumumab administered SC to standard MM regimens will improve responses compared to response data observed in completed phase 3 studies without daratumumab. Disease evaluations will include measurements of myeloma proteins, bone marrow examinations, skeletal surveys, assessment of extramedullary plasmacytomas, and measurements of serum calcium corrected for albumin. Safety will be measured by adverse events, laboratory test results, electrocardiogram (ECGs), vital sign measurements, physical examination findings, SC injection-site assessments, and assessment of Eastern Cooperative Oncology Group (ECOG) performance status score. Study will consist of 3 phases (screening, treatment and follow-up) and duration of study is approximately 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) | Experimental | Drug: Daratumumab, Drug: Bortezomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants will receive daratumumab 1800 milligram (mg) by subcutaneous (SC) injection on Days 1, 8 and 15 of Cycles 1 to 3 (each cycle of 21 days) and on Day 1 of Cycle 4; bortezomib 1.3 milligram per square meter (mg/m^2) SC injection on Days 1, 4, 8 and 11 of Cycles 1 to 4; lenalidomide 25 mg orally on Day 1 through Day 14 of Cycles 1 to 4 and dexamethasone 20 mg orally or intravenously on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4. |
| D + Bortezomib + Melphalan + Prednisone (D-VMP) | Experimental | Drug: Daratumumab, Drug: Bortezomib, Drug: Melphalan, Drug: PrednisoneParticipants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1 then on Days 1 and 22 in Cycles 2 to 9 and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; bortezomib 1.3 mg/m^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m^2 orally on Days 1 to 4 of cycles 1 to 9. |
| Daratumumab + Lenalidomide + Dexamethasone (D-Rd) | Experimental | Drug: Daratumumab, Drug: Lenalidomide, Drug: DexamethasoneParticipants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 then on Day 1 and 15 of Cycles 3 to 6 and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or end of study. |
| Daratumumab + Carfilzomib + Dexamethasone (D-Kd) | Experimental | Drug: Daratumumab, Drug: Dexamethasone, Drug: CarfilzomibParticipants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days) then on Day 1 and 15 of Cycles 3 to 6 and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; Carfilzomib 20 mg/m^2 intravenously (IV) on Day 1 of Cycle 1 only then 70 mg/m^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or IV weekly for Cycles 1-9 then on Days 1, 8, 15 of each cycle for Cycles 10 and thereafter until documented progression of disease, unacceptable toxicity, or end of study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG) diagnostic criteria
- Measurable, secretory disease as defined by any of the following:
- Meets one of the sets of the following criteria:
- Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0, 1, or 2
- During the study, during dose interruptions, and for 3 months after receiving the last dose of any component of the study treatment, a female participant must agree not to donate eggs (ova, oocytes) and male participants of reproductive potential must not donate semen or sperm during the study, during dose interruptions, or for 3 months after the last dose of any study drug
Key exclusion criteria (6 listed)
- History of malignancy (other than MM) unless all treatment of that malignancy was completed at least 2 years before consent and the participant 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
- Exhibits clinical signs of meningeal involvement of MM
- Either of the following: a) Chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) is less than (<) 50 percentage (%) of predicted normal b) Moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification c) For D-Kd cohort: Known infiltrative pulmonary disease or known pulmonary hypertension
- Any of the following: a) Known to be seropositive for human immunodeficiency virus; b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (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) DNA levels. Those who are polymerase chain reaction (PCR) positive will be excluded
- Known to be seropositive for hepatitis C (Anti-HCV antibody positive or HCV-RNA quantitation positive) 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 |
|---|---|---|
| DaratumumabDaratumumab will be administered at a dose of 1800 mg by SC injection in Cycles 1 to 4 in D-VRd cohort and until documented progression of disease, unacceptable toxicity, or end of study for D-VMP, D-Rd and D-Kd cohorts. | Drug | D + Bortezomib + Melphalan + Prednisone (D-VMP), Daratumumab + Carfilzomib + Dexamethasone (D-Kd), Daratumumab + Lenalidomide + Dexamethasone (D-Rd), Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) |
| BortezomibBortezomib will be administered as 1.3 mg/m^2 SC injection in Cycles 1 to 4 in D-VRd cohort and in Cycles 1 to 9 in D-VMP cohort. | Drug | D + Bortezomib + Melphalan + Prednisone (D-VMP), Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) |
| LenalidomideLenalidomide will be administered as 25 mg capsule orally in Cycles 1 to 4 in D-VRd cohort and in all Cycles until documented progression of disease, unacceptable toxicity, or end of study in D-Rd cohort. | Drug | Daratumumab + Lenalidomide + Dexamethasone (D-Rd), Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) |
| DexamethasoneDexamethasone will be administered as 20 mg orally or intravenously in Cycles 1 to 4 in D-VRd cohort; 40 mg orally or intravenously in all cycles and thereafter until documented progression of disease, unacceptable toxicity, or end of study in D-Rd and D-Kd cohort. | Drug | Daratumumab + Carfilzomib + Dexamethasone (D-Kd), Daratumumab + Lenalidomide + Dexamethasone (D-Rd), Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) |
| MelphalanMelphalan will be administered as 9 mg/m^2 orally in Cycles 1 to 9. | Drug | D + Bortezomib + Melphalan + Prednisone (D-VMP) |
| PrednisonePrednisone will be administered as 60 mg/m^2 orally in cycles 1 to 9. | Drug | D + Bortezomib + Melphalan + Prednisone (D-VMP) |
| CarfilzomibCarfilzomib will be administered as 20 mg/m^2 IV on Day 1 of Cycle 1 only then 70 mg/m^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or end of study in D-Kd cohort. | Drug | Daratumumab + Carfilzomib + Dexamethasone (D-Kd) |
Primary outcome
D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)
Time frame: Up to 2 years 3 months
ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 milligrams (mg) per 24 hours, If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
D-VRd Cohort: Percentage of Participants With Very Good Partial Response (VGPR) or Better Response
Time frame: Up to 2 years and 3 months
VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response [sCR]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level <100 mg/24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.
9 secondary outcomes
Maximum Observed Serum Concentration (Cmax) of Daratumumab
Time frame: D-VRd: Day 4 of Cycles 1 and 4 and post treatment at Week 8; D-VMP: Day 4 of Cycles 1 and 2 and post treatment at Week 8; D-Rd and D-Kd: Day 4 of Cycles 1 and 3 and post treatment at Week 8
Percentage of Participants With Infusion-Related Reactions (IRRs)
Time frame: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With VGPR or Better Response
Time frame: From baseline up to 2 years 7 months
D-VRd Cohort: Overall Response Rate (ORR)
Time frame: Up to 2 years and 3 months
Percentage of Participants With CR or Better Response
Time frame: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months
D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)
Time frame: From baseline up to 2 years 7 months
Percentage of Participants With Anti-Daratumumab Antibodies
Time frame: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months
Percentage of Participants With Anti-rHuPH20 Antibodies
Time frame: For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months
D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With Minimal Residual Disease (MRD) Negative Rate
Time frame: Up to 2 years and 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36882409Moreau P, Chari A, Oriol A, Martinez-Lopez J, Haenel M, Touzeau C, Ailawadhi S, Besemer B, de la Rubia Comos J, Encinas C, Mateos MV, Salwender H, Rodriguez-Otero P, Hulin C, Karlin L, Sureda Balari A, Bargay J, Benboubker L, Rosinol L, Tarantolo S, Terebelo H, Yang S, Wang J, Nnane I, Qi M, Kosh M, Delioukina M, Goldschmidt H. Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS. Blood Cancer J. 2023 Mar 7;13(1):33. doi: 10.1038/s41408-023-00805-x. No abstract available.
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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
64 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daratumumab, Bortezomib and Lenalidomide in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 64 sites in 9 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 11 inclusion and 6 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: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 64 sites in United States, Spain, Brazil, Israel, United Kingdom and 4 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 12 Jan 2022). 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?
D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR) (time frame: Up to 2 years 3 months). The study lists 2 primary outcomes in all. 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 NCT03412565, 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 29 Apr 2025.