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A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03412565
Collaborator
(none)
265
Enrollment
64
Locations
4
Arms
61.2
Anticipated Duration (Months)
4.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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

Study Type:
Interventional
Actual Enrollment :
265 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter Phase 2 Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens
Actual Study Start Date :
Apr 26, 2018
Actual Primary Completion Date :
Aug 12, 2020
Anticipated Study Completion Date :
Jun 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

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.

Drug: Daratumumab
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.

Drug: Bortezomib
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.

Drug: Lenalidomide
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.

Drug: Dexamethasone
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.
Experimental: D + Bortezomib + Melphalan + Prednisone (D-VMP)

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.

Drug: Daratumumab
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.

Drug: Bortezomib
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.

Drug: Melphalan
Melphalan will be administered as 9 mg/m^2 orally in Cycles 1 to 9.

Drug: Prednisone
Prednisone will be administered as 60 mg/m^2 orally in cycles 1 to 9.
Experimental: Daratumumab + Lenalidomide + Dexamethasone (D-Rd)

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.

Drug: Daratumumab
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.

Drug: Lenalidomide
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.

Drug: Dexamethasone
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.
Experimental: Daratumumab + Carfilzomib + Dexamethasone (D-Kd)

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.

Drug: Daratumumab
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.

Drug: Dexamethasone
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.

Drug: Carfilzomib
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.

Outcome Measures

Primary Outcome Measures

  1. D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR) [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.

  2. D-VRd Cohort: Percentage of Participants With Very Good Partial Response (VGPR) or Better Response [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.

Secondary Outcome Measures

  1. Maximum Observed Serum Concentration (Cmax) of Daratumumab [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]

    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.

  2. Percentage of Participants With Infusion-Related Reactions (IRRs) [Up to 2 years and 3 months]

    Percentage of Participants with IRRs were reported. The administration-related systemic reactions are referred to as IRRs.

  3. D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With VGPR or Better Response [Up to 2 years and 3 months]

    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.

  4. D-VRd Cohort: Overall Response Rate (ORR) [Up to 2 years and 3 months]

    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.

  5. Percentage of Participants With CR or Better Response [Up to 2 years and 3 months]

    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.

  6. D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR) [Up to 2 years and 3 months]

    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.

  7. Percentage of Participants With Anti-Daratumumab Antibodies [Up to 10 months]

    Percentage of participants with antibodies to daratumumab were reported.

  8. Percentage of Participants With Anti-rHuPH20 Antibodies [Up to 10 months]

    Percentage of participants with antibodies to rHuPH20 were reported.

  9. D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With Minimal Residual Disease (MRD) Negative Rate [Up to 2 years and 3 months]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG) diagnostic criteria

  • Measurable, secretory disease as defined by any of the following:

  1. Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL); or

  2. Urine M-protein level >= 200 milligram per 24 hours (mg/24 hours); or

  3. 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:

  1. For Daratumumab + bortezomib + lenalidomide + dexamethasone (D-VRd) and Daratumumab + bortezomib + melphalan + prednisone + dexamethasone (D-VMP) regimen: newly diagnosed myeloma

  2. For Daratumumab + lenalidomide + dexamethasone (D-Rd) and Daratumumab + Carfilzomib + Dexamethasone (D-Kd) regimen: relapsed or refractory disease

  3. 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

Exclusion Criteria:

  • 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Cancer Center of Central Connecticut - Southington Southington Connecticut United States 06489-3237
2 Mayo Clinic in Florida Jacksonville Florida United States 32224
3 UF Health Cancer Center at Orlando Health Orlando Florida United States 32806
4 Karmonos Cancer Institute Detroit Michigan United States 48201
5 Providence Cancer Center Southfield Michigan United States 48075
6 Billings Clinic Billings Montana United States 59101
7 Nebraska Hematology and Oncology Lincoln Nebraska United States 68506
8 Southeast Nebraska Cancer Center Lincoln Nebraska United States 68510
9 Nebraska Cancer Specialists Omaha Nebraska United States 68130
10 San Juan Oncology Associates Farmington New Mexico United States 87401
11 NYU Winthrop Mineola New York United States 11501
12 Mt. Sinai School of Medicine New York New York United States 10029
13 Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center Winston-Salem North Carolina United States 27157
14 Avera Medical Group - Oncology & Hematology Sioux Falls South Dakota United States 57105
15 Utah Cancer Specialists Salt Lake City Utah United States 84121
16 University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic Charlottesville Virginia United States 22903
17 Liga Norte Riograndense Contra O Cancer Natal Brazil 59062-000
18 Centro de Pesquisa do Instituto do Câncer- Hospital São Vicente de Paulo Passo Fundo Brazil 99010-090
19 Instituto Nacional do Cancer - INCA Rio de Janeiro Brazil 20230-130
20 Universidade Federal de Sao Paulo Sao Paulo Brazil 04037-002
21 Hospital do Servidor Publico Estadual - IAMSPE Sao Paulo Brazil
22 Clinica Sao Germano São Paulo Brazil 01455-010
23 Fakultni nemocnice Brno Brno Czechia 625 00
24 Fakultni nemocnice Hradec Kralove Hradec Kralove Czechia 500 05
25 Fakultni nemocnice Ostrava Ostrava Czechia 70852
26 Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie Praha 2 Czechia 128 08
27 CHU de Nantes hôtel-Dieu Nantes Cedex 1 France 44093
28 CHU de Bordeaux - Hôpital Haut-Lévêque Pessac cedex France 33604
29 Centre hospitalier Lyon-Sud Pierre-Bénite France 69495
30 CHU Bretonneau Tours Cedex 9 France 37044
31 CHU Nancy Brabois Vandoeuvre Les Nancy France 54511
32 Klinikum Chemnitz gGmbH Chemnitz Germany 09113
33 Universitaetsklinikum Hamburg Eppendorf Hamburg Germany 20246
34 Asklepios Klinik Altona Hamburg Germany 22763
35 Universitaetsklinikum Heidelberg Heidelberg Germany 69120
36 Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II, Tübingen Germany 72076
37 Rambam Medical Center Haifa Israel 31096
38 Carmel Medical Center Haifa Israel 3436212
39 Hadassah Medical Center Jerusalem Israel 9112001
40 Galilee Medical Center Nahariya Israel 22100
41 Sheba Medical Center Ramat Gan Israel 52621
42 Tel-Aviv Sourasky Medical Center Tel-Aviv Israel 64239
43 Kanazawa University Hospital Kanazawa Japan 920-8641
44 Matsuyama Red Cross Hospital Matsuyama Japan 790-8524
45 Nagoya City University Hospital Nagoya Japan 467-8602
46 Japanese Red Cross Medical Center Shibuya Japan 150-8935
47 Inst. Cat. D'Oncologia-Badalona Badalona Spain 08916
48 Hosp. Clinic I Provincial de Barcelona Barcelona Spain 08036
49 Inst. Cat. Doncologia-H Duran I Reynals Barcelona Spain 08908
50 Hosp. Univ. Vall D Hebron Barcelona Spain 8035
51 Hosp. Gral. Univ. Gregorio Marañon Madrid Spain 28007
52 Clinica Univ. de Navarra Madrid Spain 28027
53 Hosp. Univ. Ramon Y Cajal Madrid Spain 28034
54 Hosp. Univ. 12 de Octubre Madrid Spain 28041
55 Hosp. Son Llatzer Mallorca Spain 07198
56 Clinica Univ. de Navarra Pamplona Spain 31008
57 Hosp. Clinico Univ. de Salamanca Salamanca Spain 37007
58 Hosp. Univ. Dr. Peset Valencia Spain 46017
59 Heart of England NHS Foundation Trust Birmingham United Kingdom B9 5SS
60 Royal Bournemouth Hospital Bournemouth United Kingdom BH7 7DW
61 Kent and Canterbury Hospital Canterbury United Kingdom CT1 3NG
62 Manchester Royal Infirmary Manchester United Kingdom M13 9WL
63 Derriford Hospital Plymouth United Kingdom PL6 8DH
64 Royal Stoke University Hospital Stoke on Trent United Kingdom ST4 6QG

Sponsors and Collaborators

  • Janssen Research & Development, LLC

Investigators

  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT03412565
Other Study ID Numbers:
  • CR108435
  • 2017-004203-41
  • 54767414MMY2040
First Posted:
Jan 26, 2018
Last Update Posted:
Aug 12, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Prednisone
Lenalidomide
Bortezomib
Melphalan
Daratumumab

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) D + Bortezomib + Melphalan + Prednisone (D-VMP) Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm/Group Description Participants received daratumumab 1800 milligrams (mg) as a 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 milligrams 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 (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4. Participants received 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 up to 2 years and 3 months; 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months.
Period Title: Overall Study
STARTED 67 67 65 66
COMPLETED 66 2 3 12
NOT COMPLETED 1 65 62 54

Baseline Characteristics

Arm/Group Title Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) D + Bortezomib + Melphalan + Prednisone (D-VMP) Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd) Total
Arm/Group Description Participants received daratumumab 1800 milligrams (mg) as a 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 milligrams 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 (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4. Participants received 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 up to 2 years and 3 months; 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months. Total of all reporting groups
Overall Participants 67 67 65 66 265
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
57.3
(9.47)
74.9
(4.54)
66.8
(9.58)
61
(9.77)
65
(10.87)
Sex: Female, Male (Count of Participants)
Female
19
28.4%
36
53.7%
20
30.8%
32
48.5%
107
40.4%
Male
48
71.6%
31
46.3%
45
69.2%
34
51.5%
158
59.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
3
4.5%
6
9%
0
0%
7
10.6%
16
6%
Not Hispanic or Latino
34
50.7%
39
58.2%
45
69.2%
43
65.2%
161
60.8%
Unknown or Not Reported
30
44.8%
22
32.8%
20
30.8%
16
24.2%
88
33.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
0
0%
Asian
0
0%
5
7.5%
0
0%
0
0%
5
1.9%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
0
0%
Black or African American
5
7.5%
1
1.5%
2
3.1%
2
3%
10
3.8%
White
38
56.7%
46
68.7%
45
69.2%
48
72.7%
177
66.8%
More than one race
0
0%
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
24
35.8%
15
22.4%
18
27.7%
16
24.2%
73
27.5%
Region of Enrollment (Count of Participants)
BRAZIL
1
1.5%
4
6%
0
0%
0
0%
5
1.9%
CZECH REPUBLIC
4
6%
4
6%
15
23.1%
0
0%
23
8.7%
FRANCE
26
38.8%
21
31.3%
17
26.2%
15
22.7%
79
29.8%
GERMANY
0
0%
0
0%
0
0%
19
28.8%
19
7.2%
ISRAEL
0
0%
7
10.4%
14
21.5%
0
0%
21
7.9%
JAPAN
0
0%
4
6%
0
0%
0
0%
4
1.5%
SPAIN
11
16.4%
19
28.4%
0
0%
25
37.9%
55
20.8%
UNITED KINGDOM
9
13.4%
8
11.9%
12
18.5%
0
0%
29
10.9%
UNITED STATES
16
23.9%
0
0%
7
10.8%
7
10.6%
30
11.3%

Outcome Measures

1. Primary Outcome
Title D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)
Description 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.
Time Frame Up to 2 years 3 months

Outcome Measure Data

Analysis Population Description
All treated analysis set included all participants who have received at least 1 dose of study treatment. This primary outcome measure (OM) was planned to be analyzed for D-VMP, D-Rd and D-Kd cohorts only.
Arm/Group Title Daratumumab (D) + Bortezomib + Melphalan + Prednisone (D-VMP) Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm/Group Description Participants received 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 up to 2 years and 3 months; 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months.
Measure Participants 67 65 66
Number (90% Confidence Interval) [percentage of participants]
88.1
131.5%
90.8
135.5%
84.8
130.5%
2. Primary Outcome
Title D-VRd Cohort: Percentage of Participants With Very Good Partial Response (VGPR) or Better Response
Description 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.
Time Frame Up to 2 years and 3 months

Outcome Measure Data

Analysis Population Description
All treated analysis set included all participants who have received at least 1 dose of study treatment. This primary outcome measure (OM) was planned to be analyzed for D-VRd cohort only.
Arm/Group Title Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)
Arm/Group Description Participants received daratumumab 1800 milligrams (mg) as a 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 milligrams 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 (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4.
Measure Participants 67
Number (90% Confidence Interval) [percentage of participants]
71.6
106.9%
3. Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of Daratumumab
Description 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.
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

Outcome Measure Data

Analysis Population Description
Pharmacokinetics (PK) analysis set: participants who received at least 1 dose of daratumumab SC and had at least 1 PK sample value after first dose. 'N' (number of participants analyzed): participants evaluated for this OM; 'n' (number analyzed): participants analyzed at specific timepoints. The "0" in the number analyzed field indicates that no participant was evaluable for PK at that timepoint.
Arm/Group Title Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) D-VMP Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm/Group Description Participants received daratumumab 1800 milligrams (mg) as a 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 milligrams 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 (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4. Participants received 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 up to 2 years and 3 months; 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months.
Measure Participants 60 66 56 57
Cycle 1 Day 4
100
(48.5)
98.6
(51.6)
108
(49.9)
137
(56.7)
Cycle 2 Day 4
612
(256)
Cycle 3 Day 4
648
(238)
869
(274)
Cycle 4 Day 4
746
(275)
Post-treatment Phase Week 8
263
(190)
162
(NA)
49.3
(109)
4. Secondary Outcome
Title Percentage of Participants With Infusion-Related Reactions (IRRs)
Description Percentage of Participants with IRRs were reported. The administration-related systemic reactions are referred to as IRRs.
Time Frame Up to 2 years and 3 months

Outcome Measure Data

Analysis Population Description
All treated analysis set included all participants who have received at least 1 dose of study treatment.
Arm/Group Title Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) D-VMP Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm/Group Description Participants received daratumumab 1800 milligrams (mg) as a 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 milligrams 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 (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4. Participants received 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 up to 2 years and 3 months; 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months.
Measure Participants 67 67 65 66
Number (90% Confidence Interval) [percentage of participants]
9.0
13.4%
9.0
13.4%
4.6
7.1%
4.5
6.8%
5. Secondary Outcome
Title D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With VGPR or Better Response
Description 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.
Time Frame Up to 2 years and 3 months

Outcome Measure Data

Analysis Population Description
All treated analysis set included all participants who have received at least 1 dose of study treatment. This secondary OM was planned to be analyzed for D-VMP, D-Rd and D-Kd cohorts only.
Arm/Group Title D-VMP Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm/Group Description Participants received 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 up to 2 years and 3 months; 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months.
Measure Participants 67 65 66
Number (90% Confidence Interval) [percentage of participants]
64.2
95.8%
64.6
96.4%
77.3
118.9%
6. Secondary Outcome
Title D-VRd Cohort: Overall Response Rate (ORR)
Description 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.
Time Frame Up to 2 years and 3 months

Outcome Measure Data

Analysis Population Description
All treated analysis set included all participants who have received at least 1 dose of study treatment. This secondary OM was planned to be analyzed for D-VRd cohort only.
Arm/Group Title Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)
Arm/Group Description Participants received daratumumab 1800 milligrams (mg) as a 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 milligrams 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 (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4.
Measure Participants 67
Number (90% Confidence Interval) [percentage of participants]
97.0
144.8%
7. Secondary Outcome
Title Percentage of Participants With CR or Better Response
Description 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.
Time Frame Up to 2 years and 3 months

Outcome Measure Data

Analysis Population Description
All treated analysis set included all participants who have received at least 1 dose of study treatment.
Arm/Group Title Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) D-VMP Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm/Group Description Participants received daratumumab 1800 milligrams (mg) as a 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 milligrams 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 (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4. Participants received 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 up to 2 years and 3 months; 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months.
Measure Participants 67 67 65 66
Number (90% Confidence Interval) [percentage of participants]
16.4
24.5%
17.9
26.7%
18.5
28.5%
37.9
57.4%
8. Secondary Outcome
Title D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)
Description 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.
Time Frame Up to 2 years and 3 months

Outcome Measure Data

Analysis Population Description
All treated analysis set included all participants who have received at least 1 dose of study treatment. This secondary OM was planned to be analyzed for D-VMP, D-Rd and D-Kd cohorts.
Arm/Group Title D-VMP Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm/Group Description Participants received 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 up to 2 years and 3 months; 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months.
Measure Participants 67 65 66
Median (Full Range) [months]
NA
NA
NA
9. Secondary Outcome
Title Percentage of Participants With Anti-Daratumumab Antibodies
Description Percentage of participants with antibodies to daratumumab were reported.
Time Frame Up to 10 months

Outcome Measure Data

Analysis Population Description
Immunogenicity-evaluable analysis set was defined as all participants who received at least 1 dose administration of daratumumab SC and had at least 1 immunogenicity sample for detection of anti-daratumumab antibodies after the first dose.
Arm/Group Title Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) D-VMP Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm/Group Description Participants received daratumumab 1800 milligrams (mg) as a 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 milligrams 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 (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4. Participants received 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 up to 2 years and 3 months; 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months.
Measure Participants 65 64 61 63
Number [percentage of participants]
0
0%
0
0%
0
0%
0
0%
10. Secondary Outcome
Title Percentage of Participants With Anti-rHuPH20 Antibodies
Description Percentage of participants with antibodies to rHuPH20 were reported.
Time Frame Up to 10 months

Outcome Measure Data

Analysis Population Description
Immunogenicity-evaluable analysis set for rHuPH20 is defined as all participants who received at least one dose of daratumumab SC and had appropriate plasma samples for detection of antibodies to rHuPH20 (at least 1 sample after the start of the first dose of daratumumab SC).
Arm/Group Title Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) D-VMP Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm/Group Description Participants received daratumumab 1800 milligrams (mg) as a 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 milligrams 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 (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4. Participants received 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 up to 2 years and 3 months; 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months.
Measure Participants 66 61 60 62
Number [percentage of participants]
6.1
9.1%
4.9
7.3%
1.7
2.6%
4.8
7.3%
11. Secondary Outcome
Title D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With Minimal Residual Disease (MRD) Negative Rate
Description 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.
Time Frame Up to 2 years and 3 months

Outcome Measure Data

Analysis Population Description
All treated analysis set included all participants who have received at least 1 dose of study treatment. This secondary OM was planned to be analyzed for D-VMP, D-Rd and D-Kd cohorts only.
Arm/Group Title D-VMP Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm/Group Description Participants received 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months.
Measure Participants 67 65 66
Number (90% Confidence Interval) [percentage of participants]
25.4
37.9%
21.5
32.1%
27.3
42%

Adverse Events

Time Frame Up to 2 years and 3 months
Adverse Event Reporting Description
Arm/Group Title Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) D + Bortezomib + Melphalan + Prednisone (D-VMP) Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Arm/Group Description Participants received daratumumab 1800 milligrams (mg) as a 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 milligrams 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 (IV) on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4. Participants received 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 up to 2 years and 3 months; 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. Participants received 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 up to 2 years and 3 months; 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 up to 2 years and 3 months. Participants received 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 up to 2 years and 3 months; Carfilzomib 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 up to 2 years and 3 months and dexamethasone 40 mg orally or IV weekly for Cycles 1-9, then on Days 1, 8, 15 of each cycle for Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or up to 2 years and 3 months.
All Cause Mortality
Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) D + Bortezomib + Melphalan + Prednisone (D-VMP) Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/67 (1.5%) 2/67 (3%) 2/65 (3.1%) 4/66 (6.1%)
Serious Adverse Events
Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) D + Bortezomib + Melphalan + Prednisone (D-VMP) Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 19/67 (28.4%) 25/67 (37.3%) 26/65 (40%) 18/66 (27.3%)
Blood and lymphatic system disorders
Anaemia 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Febrile Neutropenia 1/67 (1.5%) 2/67 (3%) 1/65 (1.5%) 0/66 (0%)
Neutropenia 0/67 (0%) 0/67 (0%) 3/65 (4.6%) 0/66 (0%)
Thrombocytopenia 1/67 (1.5%) 2/67 (3%) 1/65 (1.5%) 0/66 (0%)
Cardiac disorders
Atrial Fibrillation 1/67 (1.5%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Atrial Flutter 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Cardiac Failure 0/67 (0%) 1/67 (1.5%) 2/65 (3.1%) 1/66 (1.5%)
Left Ventricular Dysfunction 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Myocardial Infarction 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Eye disorders
Ophthalmic Vein Thrombosis 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Gastrointestinal disorders
Diarrhoea 0/67 (0%) 1/67 (1.5%) 2/65 (3.1%) 0/66 (0%)
Enterocolitis 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Nausea 1/67 (1.5%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Rectal Haemorrhage 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Vomiting 2/67 (3%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
General disorders
Chills 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Fatigue 2/67 (3%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
General Physical Health Deterioration 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Non-Cardiac Chest Pain 0/67 (0%) 1/67 (1.5%) 1/65 (1.5%) 0/66 (0%)
Performance Status Decreased 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Pyrexia 4/67 (6%) 5/67 (7.5%) 2/65 (3.1%) 2/66 (3%)
Infections and infestations
Bronchitis 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Campylobacter Gastroenteritis 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Central Nervous System Infection 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Clostridium Difficile Colitis 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Covid-19 0/67 (0%) 0/67 (0%) 0/65 (0%) 2/66 (3%)
Gastroenteritis 0/67 (0%) 1/67 (1.5%) 1/65 (1.5%) 0/66 (0%)
Infection 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Infective Exacerbation of Chronic Obstructive Airways Disease 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Influenza 0/67 (0%) 1/67 (1.5%) 3/65 (4.6%) 1/66 (1.5%)
Lower Respiratory Tract Infection 1/67 (1.5%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Lung Infection 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Neutropenic Sepsis 0/67 (0%) 2/67 (3%) 0/65 (0%) 0/66 (0%)
Pneumococcal Sepsis 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Pneumocystis Jirovecii Pneumonia 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Pneumonia 1/67 (1.5%) 3/67 (4.5%) 4/65 (6.2%) 2/66 (3%)
Sepsis 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 1/66 (1.5%)
Upper Respiratory Tract Infection 0/67 (0%) 0/67 (0%) 2/65 (3.1%) 0/66 (0%)
Urinary Tract Infection 1/67 (1.5%) 1/67 (1.5%) 0/65 (0%) 1/66 (1.5%)
Urosepsis 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Viral Pharyngitis 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Injury, poisoning and procedural complications
Fall 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Hip Fracture 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Wrist Fracture 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Investigations
Alanine Aminotransferase Increased 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Body Temperature Increased 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Oxygen Saturation Decreased 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Respirovirus Test Positive 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Transaminases Increased 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Metabolism and nutrition disorders
Diabetic Metabolic Decompensation 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Hypercalcaemia 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Hypercreatininaemia 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Hyperkalaemia 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Hyponatraemia 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 1/66 (1.5%)
Musculoskeletal and connective tissue disorders
Arthralgia 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Back Pain 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 1/66 (1.5%)
Bone Pain 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Muscular Weakness 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Musculoskeletal Chest Pain 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Osteonecrosis 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Spinal Pain 1/67 (1.5%) 1/67 (1.5%) 0/65 (0%) 1/66 (1.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasma Cell Myeloma 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Nervous system disorders
Cerebral Small Vessel Ischaemic Disease 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Incoherent 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Loss of Consciousness 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Spinal Cord Compression 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Syncope 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Thalamic Infarction 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Vith Nerve Paresis 0/67 (0%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Renal and urinary disorders
Acute Kidney Injury 0/67 (0%) 1/67 (1.5%) 2/65 (3.1%) 0/66 (0%)
Renal Failure 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Renal Impairment 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Hypoxia 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Pneumonitis 1/67 (1.5%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Pulmonary Embolism 2/67 (3%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Pulmonary Hypertension 0/67 (0%) 0/67 (0%) 1/65 (1.5%) 0/66 (0%)
Respiratory Failure 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 1/66 (1.5%)
Skin and subcutaneous tissue disorders
Hyperhidrosis 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Rash Maculo-Papular 0/67 (0%) 1/67 (1.5%) 0/65 (0%) 0/66 (0%)
Rash Pruritic 1/67 (1.5%) 0/67 (0%) 0/65 (0%) 0/66 (0%)
Vascular disorders
Hypotension 1/67 (1.5%) 2/67 (3%) 0/65 (0%) 0/66 (0%)
Other (Not Including Serious) Adverse Events
Daratumumab (D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd) D + Bortezomib + Melphalan + Prednisone (D-VMP) Daratumumab + Lenalidomide + Dexamethasone (D-Rd) Daratumumab + Carfilzomib + Dexamethasone (D-Kd)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 66/67 (98.5%) 66/67 (98.5%) 64/65 (98.5%) 66/66 (100%)
Blood and lymphatic system disorders
Anaemia 12/67 (17.9%) 24/67 (35.8%) 17/65 (26.2%) 24/66 (36.4%)
Leukopenia 9/67 (13.4%) 8/67 (11.9%) 10/65 (15.4%) 6/66 (9.1%)
Lymphopenia 13/67 (19.4%) 14/67 (20.9%) 10/65 (15.4%) 12/66 (18.2%)
Neutropenia 25/67 (37.3%) 25/67 (37.3%) 38/65 (58.5%) 15/66 (22.7%)
Thrombocytopenia 25/67 (37.3%) 35/67 (52.2%) 20/65 (30.8%) 34/66 (51.5%)
Ear and labyrinth disorders
Vertigo 1/67 (1.5%) 2/67 (3%) 0/65 (0%) 6/66 (9.1%)
Gastrointestinal disorders
Abdominal Pain 3/67 (4.5%) 4/67 (6%) 1/65 (1.5%) 4/66 (6.1%)
Constipation 26/67 (38.8%) 23/67 (34.3%) 15/65 (23.1%) 6/66 (9.1%)
Diarrhoea 16/67 (23.9%) 19/67 (28.4%) 22/65 (33.8%) 19/66 (28.8%)
Nausea 12/67 (17.9%) 23/67 (34.3%) 7/65 (10.8%) 14/66 (21.2%)
Odynophagia 3/67 (4.5%) 2/67 (3%) 1/65 (1.5%) 4/66 (6.1%)
Vomiting 6/67 (9%) 14/67 (20.9%) 5/65 (7.7%) 10/66 (15.2%)
General disorders
Asthenia 10/67 (14.9%) 15/67 (22.4%) 17/65 (26.2%) 14/66 (21.2%)
Chills 8/67 (11.9%) 3/67 (4.5%) 3/65 (4.6%) 2/66 (3%)
Fatigue 18/67 (26.9%) 9/67 (13.4%) 16/65 (24.6%) 13/66 (19.7%)
Injection Site Erythema 9/67 (13.4%) 5/67 (7.5%) 0/65 (0%) 4/66 (6.1%)
Malaise 0/67 (0%) 4/67 (6%) 1/65 (1.5%) 0/66 (0%)
Oedema Peripheral 13/67 (19.4%) 8/67 (11.9%) 5/65 (7.7%) 11/66 (16.7%)
Pyrexia 22/67 (32.8%) 18/67 (26.9%) 14/65 (21.5%) 14/66 (21.2%)
Infections and infestations
Bronchitis 2/67 (3%) 8/67 (11.9%) 7/65 (10.8%) 7/66 (10.6%)
Herpes Zoster 0/67 (0%) 5/67 (7.5%) 1/65 (1.5%) 1/66 (1.5%)
Nasopharyngitis 2/67 (3%) 3/67 (4.5%) 3/65 (4.6%) 16/66 (24.2%)
Pneumonia 3/67 (4.5%) 4/67 (6%) 3/65 (4.6%) 2/66 (3%)
Rhinitis 0/67 (0%) 2/67 (3%) 2/65 (3.1%) 5/66 (7.6%)
Upper Respiratory Tract Infection 5/67 (7.5%) 14/67 (20.9%) 16/65 (24.6%) 11/66 (16.7%)
Urinary Tract Infection 0/67 (0%) 4/67 (6%) 4/65 (6.2%) 1/66 (1.5%)
Investigations
Alanine Aminotransferase Increased 3/67 (4.5%) 2/67 (3%) 3/65 (4.6%) 7/66 (10.6%)
Blood Alkaline Phosphatase Increased 1/67 (1.5%) 4/67 (6%) 2/65 (3.1%) 5/66 (7.6%)
Blood Creatinine Increased 2/67 (3%) 3/67 (4.5%) 7/65 (10.8%) 2/66 (3%)
Gamma-Glutamyltransferase Increased 1/67 (1.5%) 4/67 (6%) 0/65 (0%) 8/66 (12.1%)
Weight Decreased 2/67 (3%) 5/67 (7.5%) 6/65 (9.2%) 1/66 (1.5%)
Metabolism and nutrition disorders
Decreased Appetite 2/67 (3%) 10/67 (14.9%) 4/65 (6.2%) 4/66 (6.1%)
Hyperglycaemia 1/67 (1.5%) 1/67 (1.5%) 7/65 (10.8%) 6/66 (9.1%)
Hypocalcaemia 5/67 (7.5%) 4/67 (6%) 6/65 (9.2%) 4/66 (6.1%)
Hypokalaemia 2/67 (3%) 5/67 (7.5%) 5/65 (7.7%) 1/66 (1.5%)
Musculoskeletal and connective tissue disorders
Arthralgia 1/67 (1.5%) 6/67 (9%) 4/65 (6.2%) 5/66 (7.6%)
Back Pain 7/67 (10.4%) 13/67 (19.4%) 8/65 (12.3%) 10/66 (15.2%)
Bone Pain 0/67 (0%) 4/67 (6%) 1/65 (1.5%) 6/66 (9.1%)
Muscle Spasms 4/67 (6%) 1/67 (1.5%) 18/65 (27.7%) 6/66 (9.1%)
Musculoskeletal Chest Pain 1/67 (1.5%) 6/67 (9%) 3/65 (4.6%) 7/66 (10.6%)
Musculoskeletal Pain 1/67 (1.5%) 2/67 (3%) 2/65 (3.1%) 7/66 (10.6%)
Myalgia 0/67 (0%) 2/67 (3%) 4/65 (6.2%) 2/66 (3%)
Pain in Extremity 6/67 (9%) 3/67 (4.5%) 2/65 (3.1%) 4/66 (6.1%)
Spinal Pain 1/67 (1.5%) 0/67 (0%) 1/65 (1.5%) 4/66 (6.1%)
Nervous system disorders
Dizziness 6/67 (9%) 6/67 (9%) 5/65 (7.7%) 3/66 (4.5%)
Dysgeusia 3/67 (4.5%) 2/67 (3%) 4/65 (6.2%) 0/66 (0%)
Headache 7/67 (10.4%) 4/67 (6%) 4/65 (6.2%) 15/66 (22.7%)
Paraesthesia 2/67 (3%) 6/67 (9%) 3/65 (4.6%) 6/66 (9.1%)
Peripheral Sensory Neuropathy 28/67 (41.8%) 23/67 (34.3%) 9/65 (13.8%) 7/66 (10.6%)
Tremor 4/67 (6%) 3/67 (4.5%) 4/65 (6.2%) 2/66 (3%)
Psychiatric disorders
Anxiety 2/67 (3%) 1/67 (1.5%) 3/65 (4.6%) 5/66 (7.6%)
Insomnia 12/67 (17.9%) 13/67 (19.4%) 10/65 (15.4%) 22/66 (33.3%)
Irritability 1/67 (1.5%) 1/67 (1.5%) 1/65 (1.5%) 4/66 (6.1%)
Respiratory, thoracic and mediastinal disorders
Cough 5/67 (7.5%) 8/67 (11.9%) 5/65 (7.7%) 12/66 (18.2%)
Dyspnoea 9/67 (13.4%) 2/67 (3%) 12/65 (18.5%) 11/66 (16.7%)
Dyspnoea Exertional 3/67 (4.5%) 1/67 (1.5%) 1/65 (1.5%) 4/66 (6.1%)
Productive Cough 0/67 (0%) 5/67 (7.5%) 2/65 (3.1%) 4/66 (6.1%)
Rhinorrhoea 0/67 (0%) 2/67 (3%) 0/65 (0%) 4/66 (6.1%)
Skin and subcutaneous tissue disorders
Erythema 4/67 (6%) 5/67 (7.5%) 1/65 (1.5%) 4/66 (6.1%)
Pruritus 4/67 (6%) 7/67 (10.4%) 2/65 (3.1%) 4/66 (6.1%)
Rash 9/67 (13.4%) 8/67 (11.9%) 5/65 (7.7%) 5/66 (7.6%)
Rash Generalised 4/67 (6%) 2/67 (3%) 3/65 (4.6%) 0/66 (0%)
Rash Maculo-Papular 3/67 (4.5%) 3/67 (4.5%) 4/65 (6.2%) 1/66 (1.5%)
Vascular disorders
Hypertension 1/67 (1.5%) 9/67 (13.4%) 1/65 (1.5%) 21/66 (31.8%)
Hypotension 3/67 (4.5%) 4/67 (6%) 4/65 (6.2%) 2/66 (3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.

Results Point of Contact

Name/Title GLOBAL MEDICAL HEAD
Organization Janssen Research & Development, LLC
Phone 844-434-4210
Email ClinicalTrialDisclosure@its.jnj.com
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT03412565
Other Study ID Numbers:
  • CR108435
  • 2017-004203-41
  • 54767414MMY2040
First Posted:
Jan 26, 2018
Last Update Posted:
Aug 12, 2022
Last Verified:
Aug 1, 2022