A Study to Evaluate Dara-CyBorD in Previously Untreated and Relapsed Subjects With Multiple Myeloma

Sponsor
Janssen Scientific Affairs, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02951819
Collaborator
(none)
101
Enrollment
26
Locations
1
Arm
45.2
Actual Duration (Months)
3.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate complete response plus (+) very good partial response (CR+VGPR) rate following 4 cycles of induction therapy of daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD), in previously untreated subjects, and in relapsed subjects with multiple myeloma, as defined by the International Myeloma Working Group (IMWG) criteria.

Study Design

Study Type:
Interventional
Actual Enrollment :
101 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Daratumumab Plus Cyclophosphamide, Bortezomib and Dexamethasone (Dara-CyBorD) in Previously Untreated and Relapsed Subjects With Multiple Myeloma
Actual Study Start Date :
Nov 9, 2016
Actual Primary Completion Date :
Mar 8, 2018
Actual Study Completion Date :
Aug 17, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Dara-CyBorD

Subjects will receive Daratumumab along with Cyclophosphamide, Bortezomib and Dexamethasone (Dara-CyBorD) as induction on a 28-day cycle length and Daratumab and Dexamethasone on Day 1 of each cycle for 12 cycles as maintenance therapy.

Drug: Daratumumab
For induction therapy cycle 1 day 1 and day 2 doses of daratumumab will be 8 milligram/kilogram (mg/kg). Starting cycle 1 week 2 until the completion of week 8 of daratumumab patients will receive 16 mg/kg Intravenously (IV) weekly. Starting week 9 until the completion of week 24 therapy daratumumab will be administered every other week at 16 mg/kg IV. Starting week 25 and beyond for induction therapy daratumumab will be given once every 4 weeks.

Drug: Cyclophosphamide
Subjects will receive 4 to 8 cycles of oral cyclophosphamide 300 milligram per meter square (mg/m^2 ) on Days 1, 8, 15, and 22 for every 28 days.

Drug: Bortezomib
Subjects will receive 4 to 8 cycles of Bortezomib 1.5 mg/m2 subcutaneous (SC) on Days 1, 8, and 15 for every 28 days.

Drug: Dexamethasone
Subjects will be given corticosteroids (Dexamethasone) as pre-infusion therapy prior to daratumumab and for the first 8 cycles will also receive post-infusion corticosteroids (Dexamethasone).

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants Who Achieved Complete Response (CR) or Very Good Partial Response (VGPR) [After 4 cycles of Induction (Approximately 4 months)]

    Percentage of participants who achieved CR or VGPR (as per International Myeloma Working Group [IMWG] criteria) was reported. CR: negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (<) 5 percent (%) plasma cells (PC) in bone marrow. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (>=) 90% reduction in serum M-protein plus urine M-protein level < 100 milligram per 24 hours (mg/24hours).

Secondary Outcome Measures

  1. Overall Response Rate (ORR) [After 4 Cycles of Induction (4 months), at End of Induction (4 to 8 months) and at the End of Maintenance (12 months)]

    ORR: percentage of participants achieved PR or better (PR,VGPR,CR,sCR) per IMWG. CR:negative immunofixation on serum, urine, disappearance of soft tissue plasmacytomas,<5% PCs in bone marrow(BM). sCR:CR plus normal FLC ratio,absence of clonal cells in BM by immunohistochemistry, immunofluorescence. VGPR:Serum, urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein level <100 mg/24hours. PR:>=50% reduction of serum M-protein and reduction in 24hours urinary M-protein by >=90% or to <200mg/24hours. If serum, urine M-protein unmeasurable, a>=50% decrease in difference involved and uninvolved FLC levels required in place of M-protein criteria. If serum, urine M-protein not measurable, serum free light assay is not measurable,>=50% reduction in PCs required in place of M-protein,provided baseline bone marrow PCs% >=30%, if present at baseline, a >=50% reduction in size of soft tissue plasmacytomas is also required.

  2. Time to Very Good Partial Response (VGPR) or Better [Up to 36 months]

    Time to VGPR or Better response was defined as duration from the date of first dose (start of induction) to the date of initial documentation of the response (VGPR or better) which was confirmed by a repeated measurement as required by the IMWG criteria. VGPR is defined by IMWG criteria as serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (>=) 90 % reduction in serum M-protein plus urine M-protein level < 100 milligram/24 hours (mg/24 hours).

  3. Time to Partial Response (PR) or Better [Up to 12 months]

    Time to PR or Better response was defined as duration from the date of first dose (start of induction) to the date of initial documentation of the response (PR or better) which was confirmed by a repeated measurement as required by the IMWG criteria. PR is defined as per IMWG criteria as >= 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >= 90% or to < 200 mg/24hours. If the serum and urine M-protein are unmeasurable, a>= 50% decrease in the difference between involved and uninvolved Free light chain (FLC) levels is required in the 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 plasma cells is required in place of M-protein, provided baseline bone marrow plasma cells percentage was >=30%. In addition to the above listed criteria, if present at baseline, a >= 50% reduction in the size of soft tissue plasmacytomas is also required.

  4. Duration of Response (DOR) [Up to 36 months]

    DOR was defined for participants with a confirmed response (PR or better) as the duration from the date of initial documentation of a response (PR or better) according to the IMWG criteria to the date of first documented evidence of progressive disease according to the IMWG criteria or death due to progressive disease. PR:>=50% reduction of serum M-protein and reduction in 24hours urinary M-protein by >=90% or to <200 mg/24hours. If serum and urine M-protein are unmeasurable, a >=50% decrease in difference involved and uninvolved FLC levels required in place of M-protein criteria. If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in PCs is required in place of M-protein, provided baseline bone marrow PCs % 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. Progression Free Survival (PFS) [Up to 36 months]

    PFS: duration from date of first dose (start of induction) to date of first documented evidence of progressive disease (PD) based on computerized algorithm per IMWG criteria or death due to any cause, whichever occurred first. PD: 25% increase from lowest response value in one of following: Serum and urine M-component (absolute increase >=0.5 g/dL and >=200 mg/24 hours respectively);Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase>10 mg/dL);Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow PC% (absolute % >=10%); Bone marrow PC%: absolute% >10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas, Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

  6. Time to Disease Progression (TTP) [Approximately 15 months]

    TTP was defined as the time between the date of first dose (start of induction) and the date of first documented evidence of confirmed PD, as defined in the IMWG response criteria. PD per IMWG criteria: Increase of 25% from lowest response value in one of following: Serum and urine M-component (absolute increase >=0.5 g/deciliter (dL) and >=200 mg/24 hours respectively); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase>10 mg/dL); Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow PC% (absolute % >=10%); Bone marrow PC%: absolute% >10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to the PC proliferative disorder.

  7. Overall Survival (OS) [Up to 36 months]

    Overall survival (OS) was measured from the date of first dose (start of induction) to the date of death due to any cause.

  8. Percentage of Participants With Treatment Emergent-Adverse Event [Up to 36 months]

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between administration of study drug and approximately up to 36 months that were absent before treatment or that worsened relative to pre-treatment state.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Subjects with documented multiple myeloma (MM) as defined by the International Myeloma Working Group (IMWG) 2015 criteria: Clonal bone marrow plasma cells greater than or equal to (>=) 10 percent (%) or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following CRAB (calcium level, renal dysfunction, anemia, and destructive bone lesions) features and myeloma defining events as in the protocol

  • Subjects with previously untreated myeloma or relapsed myeloma with one prior line of therapy including an induction regimen which may be followed by autologous stem cell transplantation and single agent maintenance therapy. For previously untreated subjects an emergency course of steroids (defined as no greater than 40 milligram (mg) of dexamethasone, or equivalent per day for a maximum of 4 days) is permitted. In addition, radiation therapy is permitted prior to study entry, during screening, and during Cycles 1-2 of study treatment as needed for lytic bone disease

  • Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

  • A woman of childbearing potential must have 2 negative serum (beta (β) human chorionic gonadotropin) or urine pregnancy tests during screening, the first one within 28 days prior to the first dose of study drug and the second within 24 hours prior to the first dose of study drug

  • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control example, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study drug

Exclusion Criteria:
  • Refractory to any proteasome inhibitor (PI) or the combination of PI and immunomodulatory drug (IMiD) agents (such as lenalidomide), defined as failure to respond or progression within 60 days of the end of PI therapy

  • Exhibiting clinical signs of or has a known history of meningeal or central nervous system involvement by multiple myeloma

  • Has known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) less than (<) 50 percent (%) of predicted normal

  • Has known moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification

  • Is known to be seropositive for human immunodeficiency virus, known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1MobileAlabamaUnited States
2PhoenixArizonaUnited States
3SedonaArizonaUnited States
4TucsonArizonaUnited States
5FayettevilleArkansasUnited States
6GreenbraeCaliforniaUnited States
7DenverColoradoUnited States
8NilesIllinoisUnited States
9IndianapolisIndianaUnited States
10LouisvilleKentuckyUnited States
11BethesdaMarylandUnited States
12ColumbiaMarylandUnited States
13Grand RapidsMichiganUnited States
14OmahaNebraskaUnited States
15CamdenNew JerseyUnited States
16AlbanyNew YorkUnited States
17East SetauketNew YorkUnited States
18Fresh MeadowsNew YorkUnited States
19CincinnatiOhioUnited States
20EugeneOregonUnited States
21GreenvilleSouth CarolinaUnited States
22AustinTexasUnited States
23DallasTexasUnited States
24San AntonioTexasUnited States
25TylerTexasUnited States
26SeattleWashingtonUnited States

Sponsors and Collaborators

  • Janssen Scientific Affairs, LLC

Investigators

  • Study Director: Janssen Scientific Affairs, LLC Clinical Trial, Janssen Scientific Affairs, LLC

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier:
NCT02951819
Other Study ID Numbers:
  • CR108235
  • 54767414MMY2012
First Posted:
Nov 1, 2016
Last Update Posted:
Oct 8, 2021
Last Verified:
Oct 1, 2021
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT): Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Period Title: Overall Study
STARTED8714
Treated8614
COMPLETED597
NOT COMPLETED287

Baseline Characteristics

Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)Total
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT): Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Total of all reporting groups
Overall Participants8614100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
63.6
(9)
66.4
(8.97)
64
(9)
Sex: Female, Male (Count of Participants)
Female
32
37.2%
4
28.6%
36
36%
Male
54
62.8%
10
71.4%
64
64%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
4
4.7%
1
7.1%
5
5%
Not Hispanic or Latino
79
91.9%
12
85.7%
91
91%
Unknown or Not Reported
3
3.5%
1
7.1%
4
4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
2
2.3%
0
0%
2
2%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
11
12.8%
0
0%
11
11%
White
67
77.9%
14
100%
81
81%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
6
7%
0
0%
6
6%
Region of Enrollment (Count of Participants)
UNITED STATES
86
100%
14
100%
100
100%

Outcome Measures

1. Primary Outcome
TitlePercentage of Participants Who Achieved Complete Response (CR) or Very Good Partial Response (VGPR)
DescriptionPercentage of participants who achieved CR or VGPR (as per International Myeloma Working Group [IMWG] criteria) was reported. CR: negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (<) 5 percent (%) plasma cells (PC) in bone marrow. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (>=) 90% reduction in serum M-protein plus urine M-protein level < 100 milligram per 24 hours (mg/24hours).
Time FrameAfter 4 cycles of Induction (Approximately 4 months)

Outcome Measure Data

Analysis Population Description
Response-evaluable set includes all enrolled participants who had measurable disease, received at least 1 dose of study treatment, and had at least 1 efficacy evaluation assessment.
Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Measure Participants8614
Number (95% Confidence Interval) [Percentage of Participants]
44.2
51.4%
57.1
407.9%
2. Secondary Outcome
TitleOverall Response Rate (ORR)
DescriptionORR: percentage of participants achieved PR or better (PR,VGPR,CR,sCR) per IMWG. CR:negative immunofixation on serum, urine, disappearance of soft tissue plasmacytomas,<5% PCs in bone marrow(BM). sCR:CR plus normal FLC ratio,absence of clonal cells in BM by immunohistochemistry, immunofluorescence. VGPR:Serum, urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein level <100 mg/24hours. PR:>=50% reduction of serum M-protein and reduction in 24hours urinary M-protein by >=90% or to <200mg/24hours. If serum, urine M-protein unmeasurable, a>=50% decrease in difference involved and uninvolved FLC levels required in place of M-protein criteria. If serum, urine M-protein not measurable, serum free light assay is not measurable,>=50% reduction in PCs required in place of M-protein,provided baseline bone marrow PCs% >=30%, if present at baseline, a >=50% reduction in size of soft tissue plasmacytomas is also required.
Time FrameAfter 4 Cycles of Induction (4 months), at End of Induction (4 to 8 months) and at the End of Maintenance (12 months)

Outcome Measure Data

Analysis Population Description
Response-evaluable set includes all enrolled participants who had measurable disease, received at least 1 dose of study treatment, and had at least 1 efficacy evaluation assessment.
Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Measure Participants8614
After 4 Cycles of Induction
79.1
92%
71.4
510%
At the End of Induction
87.2
101.4%
78.6
561.4%
At the End of Maintenance
89.5
104.1%
85.7
612.1%
3. Secondary Outcome
TitleTime to Very Good Partial Response (VGPR) or Better
DescriptionTime to VGPR or Better response was defined as duration from the date of first dose (start of induction) to the date of initial documentation of the response (VGPR or better) which was confirmed by a repeated measurement as required by the IMWG criteria. VGPR is defined by IMWG criteria as serum and urine M-protein detectable by immunofixation but not on electrophoresis or greater than or equal to (>=) 90 % reduction in serum M-protein plus urine M-protein level < 100 milligram/24 hours (mg/24 hours).
Time FrameUp to 36 months

Outcome Measure Data

Analysis Population Description
Response-evaluable set includes all enrolled participants who had measurable disease, received at least 1 dose of study treatment, and had at least 1 efficacy evaluation assessment.
Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Measure Participants8614
Median (95% Confidence Interval) [Months]
3.8
1.8
4. Secondary Outcome
TitleTime to Partial Response (PR) or Better
DescriptionTime to PR or Better response was defined as duration from the date of first dose (start of induction) to the date of initial documentation of the response (PR or better) which was confirmed by a repeated measurement as required by the IMWG criteria. PR is defined as per IMWG criteria as >= 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >= 90% or to < 200 mg/24hours. If the serum and urine M-protein are unmeasurable, a>= 50% decrease in the difference between involved and uninvolved Free light chain (FLC) levels is required in the 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 plasma cells is required in place of M-protein, provided baseline bone marrow plasma cells percentage was >=30%. In addition to the above listed criteria, if present at baseline, a >= 50% reduction in the size of soft tissue plasmacytomas is also required.
Time FrameUp to 12 months

Outcome Measure Data

Analysis Population Description
Response-evaluable set includes all enrolled participants who had measurable disease, received at least 1 dose of study treatment, and had at least 1 efficacy evaluation assessment.
Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Measure Participants8614
Median (95% Confidence Interval) [Months]
1.0
1.0
5. Secondary Outcome
TitleDuration of Response (DOR)
DescriptionDOR was defined for participants with a confirmed response (PR or better) as the duration from the date of initial documentation of a response (PR or better) according to the IMWG criteria to the date of first documented evidence of progressive disease according to the IMWG criteria or death due to progressive disease. PR:>=50% reduction of serum M-protein and reduction in 24hours urinary M-protein by >=90% or to <200 mg/24hours. If serum and urine M-protein are unmeasurable, a >=50% decrease in difference involved and uninvolved FLC levels required in place of M-protein criteria. If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in PCs is required in place of M-protein, provided baseline bone marrow PCs % 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 FrameUp to 36 months

Outcome Measure Data

Analysis Population Description
Population included responders (PR or better) in response-evaluable set.
Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Measure Participants7712
Median (95% Confidence Interval) [Months]
NA
20.7
6. Secondary Outcome
TitleProgression Free Survival (PFS)
DescriptionPFS: duration from date of first dose (start of induction) to date of first documented evidence of progressive disease (PD) based on computerized algorithm per IMWG criteria or death due to any cause, whichever occurred first. PD: 25% increase from lowest response value in one of following: Serum and urine M-component (absolute increase >=0.5 g/dL and >=200 mg/24 hours respectively);Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase>10 mg/dL);Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow PC% (absolute % >=10%); Bone marrow PC%: absolute% >10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas, Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Time FrameUp to 36 months

Outcome Measure Data

Analysis Population Description
Full analysis set is defined as enrolled participants who provided informed consent and met eligibility criteria.
Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Measure Participants8714
Median (95% Confidence Interval) [Months]
NA
21.7
7. Secondary Outcome
TitleTime to Disease Progression (TTP)
DescriptionTTP was defined as the time between the date of first dose (start of induction) and the date of first documented evidence of confirmed PD, as defined in the IMWG response criteria. PD per IMWG criteria: Increase of 25% from lowest response value in one of following: Serum and urine M-component (absolute increase >=0.5 g/deciliter (dL) and >=200 mg/24 hours respectively); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase>10 mg/dL); Only participants without measurable serum and urine M-protein levels, without measurable disease by FLC levels, bone marrow PC% (absolute % >=10%); Bone marrow PC%: absolute% >10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to the PC proliferative disorder.
Time FrameApproximately 15 months

Outcome Measure Data

Analysis Population Description
Full Analysis Set defined as enrolled subjects who provided informed consent and met eligibility criteria.
Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Measure Participants8714
Median (95% Confidence Interval) [Months]
NA
13.31
8. Secondary Outcome
TitleOverall Survival (OS)
DescriptionOverall survival (OS) was measured from the date of first dose (start of induction) to the date of death due to any cause.
Time FrameUp to 36 months

Outcome Measure Data

Analysis Population Description
Full analysis set is defined as enrolled participants who provided informed consent and met eligibility criteria.
Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Measure Participants8714
Median (95% Confidence Interval) [Months]
NA
NA
9. Secondary Outcome
TitlePercentage of Participants With Treatment Emergent-Adverse Event
DescriptionAn adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between administration of study drug and approximately up to 36 months that were absent before treatment or that worsened relative to pre-treatment state.
Time FrameUp to 36 months

Outcome Measure Data

Analysis Population Description
Safety Analysis Set defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT):Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy:Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
Measure Participants8614
Number [Percentage of participants]
100.0
116.3%
100.0
714.3%

Adverse Events

Time FrameUp to 36 months
Adverse Event Reporting Description Safety analysis set is defined as enrolled participants who received at least 1 dose (partial or complete) of study treatment (Dara-CyBorD).
Arm/Group TitleNewly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Arm/Group DescriptionInduction therapy:Participants received daratumumab, cyclophosphamide, bortezomib, and dexamethasone (Dara-CyBorD) as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22), Cycle 2 (Days 1,8,15,22), Cycles 3-6 (Days 1,15), Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2 (Days 1,8,15,22), Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). Consolidation therapy (CT): Participants who were considered eligible for transplant underwent autologous stem cell transplantation [ASCT] at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).Participants with RMM (defined as having achieved at least a PR with first-line therapy before progression) received treatment as-Induction therapy:Participants received Dara-CyBorD as: daratumumab 8 mg/kg IV on Cycle 1(Day 1,2) and 16 mg/kg IV on Cycle 1(Days 8,15,22),Cycle 2 (Days 1,8,15,22),Cycles 3-6(Days 1,15),Cycles 7-8(Day 1); Cyclophosphamide 300 mg/m^2 orally on Days 1,8,15,22 of each cycle (28 days); Bortezomib 1.5 mg/m^2 SC on Days 1,8,15 of each cycle; Dexamethasone 20 mg IV on Cycle 1(Day1,2,8,15,22) and orally on Cycle 1(Day 9,16,23), 40 mg IV or oral on Cycle 2(Days 1,8,15,22),Cycle 3-8 ([if with CyBorD] Days 1,8,15,22). CT: Participants who were considered eligible for transplant underwent ASCT at investigator discretion. Maintenance therapy: Daratumumab 16 mg/kg IV on Day 1 for 12 cycles or until PD, whichever occurred first; Dexamethasone 12 mg IV or oral on Day 1 of each cycle(for ASCT participants, maintenance therapy was to begin approximately 90 days after ASCT).
All Cause Mortality
Newly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total9/86 (10.5%) 7/14 (50%)
Serious Adverse Events
Newly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total28/86 (32.6%) 5/14 (35.7%)
Blood and lymphatic system disorders
Febrile Neutropenia1/86 (1.2%) 0/14 (0%)
Cardiac disorders
Atrial Fibrillation4/86 (4.7%) 0/14 (0%)
Atrial Flutter1/86 (1.2%) 0/14 (0%)
Gastrointestinal disorders
Haemorrhoidal Haemorrhage0/86 (0%) 1/14 (7.1%)
Vomiting1/86 (1.2%) 0/14 (0%)
General disorders
Fatigue1/86 (1.2%) 0/14 (0%)
Non-Cardiac Chest Pain2/86 (2.3%) 0/14 (0%)
Pyrexia2/86 (2.3%) 0/14 (0%)
Hepatobiliary disorders
Cholecystitis Acute1/86 (1.2%) 0/14 (0%)
Infections and infestations
Bacteraemia1/86 (1.2%) 0/14 (0%)
Bacterial Sepsis1/86 (1.2%) 0/14 (0%)
Bronchitis1/86 (1.2%) 0/14 (0%)
Cellulitis1/86 (1.2%) 0/14 (0%)
Diverticulitis1/86 (1.2%) 0/14 (0%)
Herpes Zoster Disseminated1/86 (1.2%) 0/14 (0%)
Influenza1/86 (1.2%) 0/14 (0%)
Otitis Externa1/86 (1.2%) 0/14 (0%)
Pneumonia2/86 (2.3%) 2/14 (14.3%)
Pneumonia Parainfluenzae Viral1/86 (1.2%) 0/14 (0%)
Pneumonia Streptococcal1/86 (1.2%) 0/14 (0%)
Urinary Tract Infection1/86 (1.2%) 0/14 (0%)
Viral Upper Respiratory Tract Infection1/86 (1.2%) 0/14 (0%)
Injury, poisoning and procedural complications
Femur Fracture1/86 (1.2%) 0/14 (0%)
Hip Fracture1/86 (1.2%) 0/14 (0%)
Pelvic Fracture1/86 (1.2%) 0/14 (0%)
Toxicity to Various Agents0/86 (0%) 1/14 (7.1%)
Metabolism and nutrition disorders
Dehydration1/86 (1.2%) 0/14 (0%)
Hyperglycaemia1/86 (1.2%) 0/14 (0%)
Hyponatraemia1/86 (1.2%) 0/14 (0%)
Musculoskeletal and connective tissue disorders
Back Pain1/86 (1.2%) 0/14 (0%)
Bone Lesion1/86 (1.2%) 0/14 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Leukaemia1/86 (1.2%) 0/14 (0%)
Nervous system disorders
Syncope1/86 (1.2%) 0/14 (0%)
Psychiatric disorders
Mental Status Changes2/86 (2.3%) 0/14 (0%)
Renal and urinary disorders
Nephrotic Syndrome1/86 (1.2%) 0/14 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure1/86 (1.2%) 0/14 (0%)
Bronchiectasis0/86 (0%) 1/14 (7.1%)
Chronic Obstructive Pulmonary Disease1/86 (1.2%) 0/14 (0%)
Laryngeal Oedema1/86 (1.2%) 0/14 (0%)
Pulmonary Embolism2/86 (2.3%) 1/14 (7.1%)
Vascular disorders
Deep Vein Thrombosis1/86 (1.2%) 0/14 (0%)
Hypotension1/86 (1.2%) 0/14 (0%)
Other (Not Including Serious) Adverse Events
Newly Diagnosed Multiple Myeloma (NDMM)Relapsed Multiple Myeloma (RMM)
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total86/86 (100%) 14/14 (100%)
Blood and lymphatic system disorders
Anaemia12/86 (14%) 1/14 (7.1%)
Hyperleukocytosis0/86 (0%) 1/14 (7.1%)
Increased Tendency to Bruise1/86 (1.2%) 0/14 (0%)
Iron Deficiency Anaemia1/86 (1.2%) 0/14 (0%)
Leukopenia8/86 (9.3%) 2/14 (14.3%)
Lymphopenia3/86 (3.5%) 0/14 (0%)
Neutropenia12/86 (14%) 3/14 (21.4%)
Thrombocytopenia5/86 (5.8%) 2/14 (14.3%)
Cardiac disorders
Atrial Fibrillation4/86 (4.7%) 0/14 (0%)
Atrial Flutter1/86 (1.2%) 0/14 (0%)
Bradycardia1/86 (1.2%) 0/14 (0%)
Cardiac Failure Congestive1/86 (1.2%) 0/14 (0%)
Palpitations3/86 (3.5%) 0/14 (0%)
Pericardial Effusion1/86 (1.2%) 0/14 (0%)
Sinus Tachycardia1/86 (1.2%) 1/14 (7.1%)
Supraventricular Tachycardia1/86 (1.2%) 0/14 (0%)
Tachycardia3/86 (3.5%) 0/14 (0%)
Ventricular Extrasystoles1/86 (1.2%) 0/14 (0%)
Ear and labyrinth disorders
Deafness0/86 (0%) 1/14 (7.1%)
Deafness Bilateral1/86 (1.2%) 0/14 (0%)
Ear Congestion2/86 (2.3%) 0/14 (0%)
Ear Discomfort2/86 (2.3%) 0/14 (0%)
Ear Pain2/86 (2.3%) 0/14 (0%)
Eustachian Tube Obstruction0/86 (0%) 1/14 (7.1%)
Excessive Cerumen Production2/86 (2.3%) 1/14 (7.1%)
Hypoacusis1/86 (1.2%) 0/14 (0%)
Middle Ear Inflammation1/86 (1.2%) 0/14 (0%)
Tinnitus3/86 (3.5%) 0/14 (0%)
Vertigo1/86 (1.2%) 0/14 (0%)
Endocrine disorders
Hypothyroidism1/86 (1.2%) 0/14 (0%)
Eye disorders
Cataract4/86 (4.7%) 0/14 (0%)
Cataract Subcapsular1/86 (1.2%) 0/14 (0%)
Chalazion2/86 (2.3%) 0/14 (0%)
Diplopia1/86 (1.2%) 0/14 (0%)
Dry Eye4/86 (4.7%) 0/14 (0%)
Eye Discharge0/86 (0%) 1/14 (7.1%)
Eye Irritation2/86 (2.3%) 0/14 (0%)
Eye Pruritus1/86 (1.2%) 0/14 (0%)
Eye Swelling1/86 (1.2%) 0/14 (0%)
Lacrimation Increased4/86 (4.7%) 2/14 (14.3%)
Ocular Hyperaemia1/86 (1.2%) 0/14 (0%)
Periorbital Oedema2/86 (2.3%) 0/14 (0%)
Photophobia2/86 (2.3%) 0/14 (0%)
Retinal Haemorrhage1/86 (1.2%) 0/14 (0%)
Swelling of Eyelid1/86 (1.2%) 0/14 (0%)
Vision Blurred4/86 (4.7%) 2/14 (14.3%)
Visual Impairment0/86 (0%) 1/14 (7.1%)
Vitreous Floaters1/86 (1.2%) 1/14 (7.1%)
Gastrointestinal disorders
Abdominal Discomfort1/86 (1.2%) 0/14 (0%)
Abdominal Distension3/86 (3.5%) 1/14 (7.1%)
Abdominal Pain8/86 (9.3%) 4/14 (28.6%)
Abdominal Pain Lower3/86 (3.5%) 0/14 (0%)
Abdominal Pain Upper5/86 (5.8%) 0/14 (0%)
Anal Incontinence1/86 (1.2%) 0/14 (0%)
Aphthous Ulcer1/86 (1.2%) 0/14 (0%)
Constipation27/86 (31.4%) 0/14 (0%)
Dental Caries1/86 (1.2%) 0/14 (0%)
Dental Discomfort1/86 (1.2%) 0/14 (0%)
Diarrhoea38/86 (44.2%) 6/14 (42.9%)
Diverticulum0/86 (0%) 1/14 (7.1%)
Dry Mouth6/86 (7%) 1/14 (7.1%)
Dyspepsia10/86 (11.6%) 2/14 (14.3%)
Dysphagia1/86 (1.2%) 0/14 (0%)
Enteritis1/86 (1.2%) 0/14 (0%)
Faeces Discoloured1/86 (1.2%) 0/14 (0%)
Flatulence1/86 (1.2%) 1/14 (7.1%)
Gastritis1/86 (1.2%) 0/14 (0%)
Gastrooesophageal Reflux Disease4/86 (4.7%) 2/14 (14.3%)
Gingival Disorder1/86 (1.2%) 0/14 (0%)
Haematochezia1/86 (1.2%) 0/14 (0%)
Haemorrhoids0/86 (0%) 1/14 (7.1%)
Hyperaesthesia Teeth1/86 (1.2%) 0/14 (0%)
Incarcerated Inguinal Hernia1/86 (1.2%) 0/14 (0%)
Irritable Bowel Syndrome1/86 (1.2%) 0/14 (0%)
Mouth Ulceration0/86 (0%) 1/14 (7.1%)
Nausea43/86 (50%) 3/14 (21.4%)
Oesophageal Pain0/86 (0%) 1/14 (7.1%)
Oesophagitis2/86 (2.3%) 1/14 (7.1%)
Oral Pain2/86 (2.3%) 0/14 (0%)
Rectal Haemorrhage2/86 (2.3%) 0/14 (0%)
Retching1/86 (1.2%) 0/14 (0%)
Stomatitis2/86 (2.3%) 1/14 (7.1%)
Swollen Tongue1/86 (1.2%) 0/14 (0%)
Toothache6/86 (7%) 0/14 (0%)
Vomiting25/86 (29.1%) 5/14 (35.7%)
Vomiting Projectile1/86 (1.2%) 0/14 (0%)
General disorders
Asthenia3/86 (3.5%) 1/14 (7.1%)
Axillary Pain2/86 (2.3%) 0/14 (0%)
Catheter Site Bruise1/86 (1.2%) 0/14 (0%)
Catheter Site Erythema1/86 (1.2%) 0/14 (0%)
Catheter Site Haemorrhage1/86 (1.2%) 0/14 (0%)
Catheter Site Pain2/86 (2.3%) 0/14 (0%)
Catheter Site Pruritus1/86 (1.2%) 0/14 (0%)
Chest Discomfort6/86 (7%) 2/14 (14.3%)
Chest Pain2/86 (2.3%) 0/14 (0%)
Chills17/86 (19.8%) 1/14 (7.1%)
Face Oedema2/86 (2.3%) 0/14 (0%)
Fatigue58/86 (67.4%) 7/14 (50%)
Feeling Cold2/86 (2.3%) 0/14 (0%)
Feeling Hot0/86 (0%) 1/14 (7.1%)
Feeling Jittery0/86 (0%) 1/14 (7.1%)
Gait Disturbance1/86 (1.2%) 1/14 (7.1%)
Influenza Like Illness2/86 (2.3%) 1/14 (7.1%)
Infusion Site Extravasation1/86 (1.2%) 1/14 (7.1%)
Injection Site Erythema3/86 (3.5%) 1/14 (7.1%)
Injection Site Pain1/86 (1.2%) 0/14 (0%)
Injection Site Rash1/86 (1.2%) 1/14 (7.1%)
Injection Site Reaction4/86 (4.7%) 0/14 (0%)
Localised Oedema1/86 (1.2%) 0/14 (0%)
Malaise2/86 (2.3%) 0/14 (0%)
Medical Device Discomfort1/86 (1.2%) 0/14 (0%)
Non-Cardiac Chest Pain4/86 (4.7%) 0/14 (0%)
Oedema1/86 (1.2%) 0/14 (0%)
Oedema Peripheral21/86 (24.4%) 1/14 (7.1%)
Pain6/86 (7%) 2/14 (14.3%)
Peripheral Swelling1/86 (1.2%) 2/14 (14.3%)
Pyrexia17/86 (19.8%) 1/14 (7.1%)
Tenderness0/86 (0%) 1/14 (7.1%)
Thirst1/86 (1.2%) 0/14 (0%)
Xerosis1/86 (1.2%) 0/14 (0%)
Hepatobiliary disorders
Hyperbilirubinaemia2/86 (2.3%) 0/14 (0%)
Immune system disorders
Anaphylactic Reaction1/86 (1.2%) 0/14 (0%)
Drug Hypersensitivity1/86 (1.2%) 1/14 (7.1%)
Hypersensitivity2/86 (2.3%) 1/14 (7.1%)
Hypogammaglobulinaemia2/86 (2.3%) 1/14 (7.1%)
Seasonal Allergy6/86 (7%) 0/14 (0%)
Infections and infestations
Acute Sinusitis1/86 (1.2%) 0/14 (0%)
Arthritis Infective1/86 (1.2%) 0/14 (0%)
Bronchiolitis0/86 (0%) 1/14 (7.1%)
Bronchitis7/86 (8.1%) 1/14 (7.1%)
Bronchitis Viral2/86 (2.3%) 0/14 (0%)
Candida Infection3/86 (3.5%) 0/14 (0%)
Cellulitis2/86 (2.3%) 0/14 (0%)
Conjunctivitis6/86 (7%) 0/14 (0%)
Cytomegalovirus Chorioretinitis1/86 (1.2%) 0/14 (0%)
Device Related Infection2/86 (2.3%) 0/14 (0%)
Diverticulitis1/86 (1.2%) 1/14 (7.1%)
Ear Infection1/86 (1.2%) 0/14 (0%)
Eye Infection1/86 (1.2%) 0/14 (0%)
Folliculitis2/86 (2.3%) 0/14 (0%)
Fungal Skin Infection1/86 (1.2%) 0/14 (0%)
Gastroenteritis Viral1/86 (1.2%) 0/14 (0%)
Gingival Abscess1/86 (1.2%) 0/14 (0%)
Herpes Zoster1/86 (1.2%) 0/14 (0%)
Herpes Zoster Disseminated2/86 (2.3%) 0/14 (0%)
Hordeolum11/86 (12.8%) 0/14 (0%)
Infected Bite1/86 (1.2%) 0/14 (0%)
Influenza6/86 (7%) 0/14 (0%)
Localised Infection1/86 (1.2%) 0/14 (0%)
Lower Respiratory Tract Infection1/86 (1.2%) 0/14 (0%)
Nasopharyngitis11/86 (12.8%) 5/14 (35.7%)
Oral Candidiasis1/86 (1.2%) 0/14 (0%)
Oral Herpes1/86 (1.2%) 0/14 (0%)
Otitis Media1/86 (1.2%) 1/14 (7.1%)
Pharyngitis1/86 (1.2%) 0/14 (0%)
Pharyngitis Streptococcal1/86 (1.2%) 0/14 (0%)
Pneumonia8/86 (9.3%) 3/14 (21.4%)
Pseudomonal Bacteraemia0/86 (0%) 1/14 (7.1%)
Rash Pustular1/86 (1.2%) 0/14 (0%)
Respiratory Tract Infection1/86 (1.2%) 0/14 (0%)
Rhinitis1/86 (1.2%) 0/14 (0%)
Sinusitis7/86 (8.1%) 4/14 (28.6%)
Skin Infection2/86 (2.3%) 0/14 (0%)
Tinea Infection1/86 (1.2%) 0/14 (0%)
Tooth Abscess1/86 (1.2%) 0/14 (0%)
Upper Respiratory Tract Infection30/86 (34.9%) 7/14 (50%)
Urinary Tract Infection7/86 (8.1%) 0/14 (0%)
Viral Infection3/86 (3.5%) 0/14 (0%)
Viral Upper Respiratory Tract Infection1/86 (1.2%) 1/14 (7.1%)
Wound Infection1/86 (1.2%) 0/14 (0%)
Injury, poisoning and procedural complications
Abdominal Wall Wound1/86 (1.2%) 0/14 (0%)
Arthropod Bite0/86 (0%) 1/14 (7.1%)
Bone Contusion1/86 (1.2%) 0/14 (0%)
Bone Fragmentation1/86 (1.2%) 0/14 (0%)
Cartilage Injury1/86 (1.2%) 0/14 (0%)
Contusion4/86 (4.7%) 1/14 (7.1%)
Eye Contusion0/86 (0%) 1/14 (7.1%)
Eyelid Contusion0/86 (0%) 1/14 (7.1%)
Fall10/86 (11.6%) 1/14 (7.1%)
Foot Fracture1/86 (1.2%) 0/14 (0%)
Lower Limb Fracture1/86 (1.2%) 0/14 (0%)
Muscle Strain3/86 (3.5%) 0/14 (0%)
Pelvic Fracture3/86 (3.5%) 0/14 (0%)
Radiation Skin Injury1/86 (1.2%) 0/14 (0%)
Rib Fracture2/86 (2.3%) 0/14 (0%)
Sunburn1/86 (1.2%) 0/14 (0%)
Thermal Burn1/86 (1.2%) 0/14 (0%)
Tooth Fracture1/86 (1.2%) 0/14 (0%)
Investigations
Alanine Aminotransferase Increased5/86 (5.8%) 0/14 (0%)
Aspartate Aminotransferase Increased6/86 (7%) 0/14 (0%)
Blood Alkaline Phosphatase Increased2/86 (2.3%) 0/14 (0%)
Blood Creatinine Increased5/86 (5.8%) 1/14 (7.1%)
Blood Pressure Increased1/86 (1.2%) 1/14 (7.1%)
Breath Sounds Abnormal1/86 (1.2%) 0/14 (0%)
Gamma-Glutamyltransferase Increased2/86 (2.3%) 0/14 (0%)
Oxygen Saturation Decreased2/86 (2.3%) 1/14 (7.1%)
Prostatic Specific Antigen Increased1/86 (1.2%) 0/14 (0%)
Weight Decreased7/86 (8.1%) 0/14 (0%)
Weight Increased8/86 (9.3%) 0/14 (0%)
Metabolism and nutrition disorders
Decreased Appetite18/86 (20.9%) 2/14 (14.3%)
Dehydration15/86 (17.4%) 2/14 (14.3%)
Diabetes Mellitus1/86 (1.2%) 0/14 (0%)
Fluid Overload2/86 (2.3%) 0/14 (0%)
Fluid Retention2/86 (2.3%) 1/14 (7.1%)
Gout2/86 (2.3%) 0/14 (0%)
Hyperglycaemia7/86 (8.1%) 0/14 (0%)
Hyperkalaemia2/86 (2.3%) 0/14 (0%)
Hyperuricaemia1/86 (1.2%) 0/14 (0%)
Hypoalbuminaemia2/86 (2.3%) 0/14 (0%)
Hypocalcaemia4/86 (4.7%) 2/14 (14.3%)
Hypokalaemia19/86 (22.1%) 1/14 (7.1%)
Hypomagnesaemia9/86 (10.5%) 2/14 (14.3%)
Hyponatraemia2/86 (2.3%) 1/14 (7.1%)
Hypophosphataemia6/86 (7%) 0/14 (0%)
Hypovolaemia1/86 (1.2%) 0/14 (0%)
Increased Appetite1/86 (1.2%) 0/14 (0%)
Iron Deficiency1/86 (1.2%) 0/14 (0%)
Type 2 Diabetes Mellitus0/86 (0%) 1/14 (7.1%)
Vitamin B12 Deficiency0/86 (0%) 1/14 (7.1%)
Vitamin D Deficiency2/86 (2.3%) 1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Arthralgia21/86 (24.4%) 3/14 (21.4%)
Arthritis0/86 (0%) 1/14 (7.1%)
Back Pain27/86 (31.4%) 6/14 (42.9%)
Bone Lesion1/86 (1.2%) 0/14 (0%)
Bone Pain10/86 (11.6%) 2/14 (14.3%)
Bursitis1/86 (1.2%) 0/14 (0%)
Costochondritis1/86 (1.2%) 0/14 (0%)
Exostosis0/86 (0%) 1/14 (7.1%)
Extremity Contracture1/86 (1.2%) 0/14 (0%)
Fibromyalgia1/86 (1.2%) 0/14 (0%)
Flank Pain3/86 (3.5%) 0/14 (0%)
Groin Pain1/86 (1.2%) 0/14 (0%)
Jaw Disorder0/86 (0%) 1/14 (7.1%)
Joint Range of Motion Decreased1/86 (1.2%) 0/14 (0%)
Joint Stiffness2/86 (2.3%) 0/14 (0%)
Joint Swelling5/86 (5.8%) 1/14 (7.1%)
Limb Discomfort1/86 (1.2%) 0/14 (0%)
Muscle Spasms8/86 (9.3%) 1/14 (7.1%)
Muscle Tightness1/86 (1.2%) 0/14 (0%)
Muscle Twitching1/86 (1.2%) 0/14 (0%)
Muscular Weakness9/86 (10.5%) 0/14 (0%)
Musculoskeletal Chest Pain9/86 (10.5%) 3/14 (21.4%)
Musculoskeletal Pain12/86 (14%) 3/14 (21.4%)
Musculoskeletal Stiffness3/86 (3.5%) 0/14 (0%)
Myalgia8/86 (9.3%) 4/14 (28.6%)
Myalgia Intercostal2/86 (2.3%) 1/14 (7.1%)
Neck Pain6/86 (7%) 1/14 (7.1%)
Osteoporosis1/86 (1.2%) 0/14 (0%)
Pain in Extremity15/86 (17.4%) 4/14 (28.6%)
Pain in Jaw3/86 (3.5%) 0/14 (0%)
Pathological Fracture1/86 (1.2%) 0/14 (0%)
Synovial Cyst0/86 (0%) 1/14 (7.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma2/86 (2.3%) 2/14 (14.3%)
Bowen's Disease0/86 (0%) 1/14 (7.1%)
Skin Papilloma0/86 (0%) 1/14 (7.1%)
Squamous Cell Carcinoma of Skin1/86 (1.2%) 0/14 (0%)
Urethral Cancer1/86 (1.2%) 0/14 (0%)
Nervous system disorders
Anosmia1/86 (1.2%) 0/14 (0%)
Burning Sensation1/86 (1.2%) 0/14 (0%)
Carpal Tunnel Syndrome2/86 (2.3%) 0/14 (0%)
Cognitive Disorder1/86 (1.2%) 0/14 (0%)
Dizziness16/86 (18.6%) 1/14 (7.1%)
Dizziness Postural1/86 (1.2%) 0/14 (0%)
Dysarthria1/86 (1.2%) 0/14 (0%)
Dysgeusia11/86 (12.8%) 2/14 (14.3%)
Headache24/86 (27.9%) 3/14 (21.4%)
Hypoaesthesia3/86 (3.5%) 0/14 (0%)
Lethargy0/86 (0%) 1/14 (7.1%)
Memory Impairment1/86 (1.2%) 0/14 (0%)
Mental Impairment1/86 (1.2%) 0/14 (0%)
Muscle Spasticity0/86 (0%) 1/14 (7.1%)
Neuralgia1/86 (1.2%) 0/14 (0%)
Neuropathy Peripheral14/86 (16.3%) 2/14 (14.3%)
Paraesthesia3/86 (3.5%) 3/14 (21.4%)
Peripheral Motor Neuropathy3/86 (3.5%) 0/14 (0%)
Peripheral Sensory Neuropathy20/86 (23.3%) 3/14 (21.4%)
Peroneal Nerve Palsy0/86 (0%) 1/14 (7.1%)
Restless Legs Syndrome3/86 (3.5%) 0/14 (0%)
Seizure1/86 (1.2%) 0/14 (0%)
Sinus Headache1/86 (1.2%) 0/14 (0%)
Somnolence1/86 (1.2%) 0/14 (0%)
Syncope1/86 (1.2%) 0/14 (0%)
Taste Disorder2/86 (2.3%) 0/14 (0%)
Tremor3/86 (3.5%) 0/14 (0%)
Vith Nerve Disorder0/86 (0%) 1/14 (7.1%)
Product Issues
Device Malfunction1/86 (1.2%) 0/14 (0%)
Psychiatric disorders
Agitation2/86 (2.3%) 0/14 (0%)
Anxiety9/86 (10.5%) 0/14 (0%)
Confusional State4/86 (4.7%) 0/14 (0%)
Depression10/86 (11.6%) 1/14 (7.1%)
Emotional Disorder1/86 (1.2%) 0/14 (0%)
Insomnia28/86 (32.6%) 2/14 (14.3%)
Irritability3/86 (3.5%) 0/14 (0%)
Mental Status Changes1/86 (1.2%) 0/14 (0%)
Nightmare1/86 (1.2%) 0/14 (0%)
Personality Change1/86 (1.2%) 0/14 (0%)
Restlessness2/86 (2.3%) 0/14 (0%)
Renal and urinary disorders
Bladder Discomfort1/86 (1.2%) 0/14 (0%)
Bladder Outlet Obstruction1/86 (1.2%) 0/14 (0%)
Bladder Spasm1/86 (1.2%) 0/14 (0%)
Dysuria6/86 (7%) 1/14 (7.1%)
Haematuria2/86 (2.3%) 0/14 (0%)
Micturition Urgency1/86 (1.2%) 0/14 (0%)
Nephrolithiasis1/86 (1.2%) 0/14 (0%)
Nephrotic Syndrome1/86 (1.2%) 0/14 (0%)
Nocturia4/86 (4.7%) 2/14 (14.3%)
Pollakiuria3/86 (3.5%) 1/14 (7.1%)
Renal Failure1/86 (1.2%) 0/14 (0%)
Renal Impairment3/86 (3.5%) 0/14 (0%)
Urinary Hesitation1/86 (1.2%) 0/14 (0%)
Urinary Incontinence2/86 (2.3%) 0/14 (0%)
Urinary Retention2/86 (2.3%) 0/14 (0%)
Urine Flow Decreased0/86 (0%) 1/14 (7.1%)
Urogenital Fistula1/86 (1.2%) 0/14 (0%)
Reproductive system and breast disorders
Breast Calcifications1/86 (1.2%) 0/14 (0%)
Breast Pain2/86 (2.3%) 0/14 (0%)
Female Genital Tract Fistula1/86 (1.2%) 0/14 (0%)
Genital Erythema1/86 (1.2%) 0/14 (0%)
Gynaecomastia1/86 (1.2%) 0/14 (0%)
Metrorrhagia1/86 (1.2%) 0/14 (0%)
Nipple Pain1/86 (1.2%) 0/14 (0%)
Pelvic Pain2/86 (2.3%) 0/14 (0%)
Prostatitis1/86 (1.2%) 0/14 (0%)
Vulvovaginal Dryness1/86 (1.2%) 0/14 (0%)
Vulvovaginal Pruritus2/86 (2.3%) 0/14 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis1/86 (1.2%) 0/14 (0%)
Bronchospasm1/86 (1.2%) 1/14 (7.1%)
Chronic Obstructive Pulmonary Disease1/86 (1.2%) 0/14 (0%)
Cough42/86 (48.8%) 6/14 (42.9%)
Dysphonia4/86 (4.7%) 0/14 (0%)
Dyspnoea27/86 (31.4%) 3/14 (21.4%)
Dyspnoea Exertional1/86 (1.2%) 0/14 (0%)
Epistaxis5/86 (5.8%) 1/14 (7.1%)
Haemoptysis1/86 (1.2%) 0/14 (0%)
Hiccups2/86 (2.3%) 2/14 (14.3%)
Hypoxia3/86 (3.5%) 0/14 (0%)
Laryngeal Inflammation1/86 (1.2%) 0/14 (0%)
Laryngospasm1/86 (1.2%) 0/14 (0%)
Lung Infiltration1/86 (1.2%) 0/14 (0%)
Nasal Congestion11/86 (12.8%) 3/14 (21.4%)
Nasal Dryness1/86 (1.2%) 0/14 (0%)
Oropharyngeal Pain12/86 (14%) 4/14 (28.6%)
Paranasal Sinus Discomfort2/86 (2.3%) 0/14 (0%)
Paranasal Sinus Hypersecretion1/86 (1.2%) 0/14 (0%)
Productive Cough8/86 (9.3%) 4/14 (28.6%)
Pulmonary Embolism1/86 (1.2%) 0/14 (0%)
Respiratory Distress0/86 (0%) 1/14 (7.1%)
Respiratory Symptom1/86 (1.2%) 0/14 (0%)
Respiratory Tract Congestion1/86 (1.2%) 2/14 (14.3%)
Rhinitis Allergic10/86 (11.6%) 0/14 (0%)
Rhinorrhoea1/86 (1.2%) 2/14 (14.3%)
Rhonchi1/86 (1.2%) 0/14 (0%)
Sinus Congestion5/86 (5.8%) 2/14 (14.3%)
Sinus Disorder1/86 (1.2%) 0/14 (0%)
Sinus Pain2/86 (2.3%) 0/14 (0%)
Sleep Apnoea Syndrome1/86 (1.2%) 1/14 (7.1%)
Sneezing1/86 (1.2%) 2/14 (14.3%)
Tachypnoea1/86 (1.2%) 0/14 (0%)
Throat Irritation3/86 (3.5%) 1/14 (7.1%)
Throat Tightness1/86 (1.2%) 0/14 (0%)
Upper Respiratory Tract Congestion1/86 (1.2%) 0/14 (0%)
Upper-Airway Cough Syndrome1/86 (1.2%) 0/14 (0%)
Wheezing8/86 (9.3%) 1/14 (7.1%)
Skin and subcutaneous tissue disorders
Actinic Keratosis1/86 (1.2%) 0/14 (0%)
Alopecia6/86 (7%) 1/14 (7.1%)
Chronic Pigmented Purpura1/86 (1.2%) 0/14 (0%)
Cold Sweat1/86 (1.2%) 0/14 (0%)
Decubitus Ulcer1/86 (1.2%) 0/14 (0%)
Dermal Cyst0/86 (0%) 1/14 (7.1%)
Dermatitis1/86 (1.2%) 0/14 (0%)
Dermatitis Contact1/86 (1.2%) 1/14 (7.1%)
Drug Eruption1/86 (1.2%) 0/14 (0%)
Dry Skin3/86 (3.5%) 1/14 (7.1%)
Eczema1/86 (1.2%) 0/14 (0%)
Erythema2/86 (2.3%) 0/14 (0%)
Hyperhidrosis5/86 (5.8%) 1/14 (7.1%)
Nail Disorder0/86 (0%) 1/14 (7.1%)
Nail Pigmentation1/86 (1.2%) 0/14 (0%)
Night Sweats4/86 (4.7%) 0/14 (0%)
Pain of Skin2/86 (2.3%) 0/14 (0%)
Petechiae1/86 (1.2%) 0/14 (0%)
Pruritus20/86 (23.3%) 1/14 (7.1%)
Psoriasis1/86 (1.2%) 0/14 (0%)
Rash12/86 (14%) 1/14 (7.1%)
Rash Follicular1/86 (1.2%) 0/14 (0%)
Rash Macular2/86 (2.3%) 0/14 (0%)
Rash Maculo-Papular2/86 (2.3%) 0/14 (0%)
Rash Pruritic1/86 (1.2%) 0/14 (0%)
Scab1/86 (1.2%) 0/14 (0%)
Skin Disorder1/86 (1.2%) 0/14 (0%)
Skin Irritation1/86 (1.2%) 0/14 (0%)
Skin Mass1/86 (1.2%) 0/14 (0%)
Stasis Dermatitis1/86 (1.2%) 0/14 (0%)
Urticaria4/86 (4.7%) 0/14 (0%)
Social circumstances
Menopause1/86 (1.2%) 0/14 (0%)
Surgical and medical procedures
Catheterisation Venous1/86 (1.2%) 0/14 (0%)
Vascular disorders
Deep Vein Thrombosis3/86 (3.5%) 0/14 (0%)
Flushing12/86 (14%) 1/14 (7.1%)
Haematoma1/86 (1.2%) 0/14 (0%)
Hot Flush2/86 (2.3%) 0/14 (0%)
Hypertension8/86 (9.3%) 1/14 (7.1%)
Hypotension6/86 (7%) 2/14 (14.3%)
Pallor1/86 (1.2%) 0/14 (0%)
Varicose Vein1/86 (1.2%) 0/14 (0%)
Venous Thrombosis1/86 (1.2%) 0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

If an investigator wishes to publish information from 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 by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.

Results Point of Contact

Name/TitleSenior Director
OrganizationJanssen Scientific Affairs
Phone844-434-4210
EmailClinicalTrialDisclosure@its.jnj.com
Responsible Party:
Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier:
NCT02951819
Other Study ID Numbers:
  • CR108235
  • 54767414MMY2012
First Posted:
Nov 1, 2016
Last Update Posted:
Oct 8, 2021
Last Verified:
Oct 1, 2021