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
26
1
45.2
3.9
0.1
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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
| Arm | Intervention/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
- 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
- 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.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mobile | Alabama | United States | ||
| 2 | Phoenix | Arizona | United States | ||
| 3 | Sedona | Arizona | United States | ||
| 4 | Tucson | Arizona | United States | ||
| 5 | Fayetteville | Arkansas | United States | ||
| 6 | Greenbrae | California | United States | ||
| 7 | Denver | Colorado | United States | ||
| 8 | Niles | Illinois | United States | ||
| 9 | Indianapolis | Indiana | United States | ||
| 10 | Louisville | Kentucky | United States | ||
| 11 | Bethesda | Maryland | United States | ||
| 12 | Columbia | Maryland | United States | ||
| 13 | Grand Rapids | Michigan | United States | ||
| 14 | Omaha | Nebraska | United States | ||
| 15 | Camden | New Jersey | United States | ||
| 16 | Albany | New York | United States | ||
| 17 | East Setauket | New York | United States | ||
| 18 | Fresh Meadows | New York | United States | ||
| 19 | Cincinnati | Ohio | United States | ||
| 20 | Eugene | Oregon | United States | ||
| 21 | Greenville | South Carolina | United States | ||
| 22 | Austin | Texas | United States | ||
| 23 | Dallas | Texas | United States | ||
| 24 | San Antonio | Texas | United States | ||
| 25 | Tyler | Texas | United States | ||
| 26 | Seattle | Washington | United 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 Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) |
|---|---|---|
| Arm/Group Description | Induction 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 | ||
| STARTED | 87 | 14 |
| Treated | 86 | 14 |
| COMPLETED | 59 | 7 |
| NOT COMPLETED | 28 | 7 |
Baseline Characteristics
| Arm/Group Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) | Total |
|---|---|---|---|
| Arm/Group Description | Induction 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 Participants | 86 | 14 | 100 |
| 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
| Title | Percentage of Participants Who Achieved Complete Response (CR) or Very Good Partial Response (VGPR) |
|---|---|
| Description | 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). |
| Time Frame | After 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 Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) |
|---|---|---|
| Arm/Group Description | Induction 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 Participants | 86 | 14 |
| Number (95% Confidence Interval) [Percentage of Participants] |
44.2
51.4%
|
57.1
407.9%
|
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | 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. |
| Time Frame | After 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 Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) |
|---|---|---|
| Arm/Group Description | Induction 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 Participants | 86 | 14 |
| 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%
|
| Title | Time to Very Good Partial Response (VGPR) or Better |
|---|---|
| Description | 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). |
| Time Frame | Up 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 Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) |
|---|---|---|
| Arm/Group Description | Induction 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 Participants | 86 | 14 |
| Median (95% Confidence Interval) [Months] |
3.8
|
1.8
|
| Title | Time to Partial Response (PR) or Better |
|---|---|
| Description | 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. |
| Time Frame | Up 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 Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) |
|---|---|---|
| Arm/Group Description | Induction 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 Participants | 86 | 14 |
| Median (95% Confidence Interval) [Months] |
1.0
|
1.0
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | 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. |
| Time Frame | Up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population included responders (PR or better) in response-evaluable set. |
| Arm/Group Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) |
|---|---|---|
| Arm/Group Description | Induction 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 Participants | 77 | 12 |
| Median (95% Confidence Interval) [Months] |
NA
|
20.7
|
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | 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. |
| Time Frame | Up 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 Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) |
|---|---|---|
| Arm/Group Description | Induction 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 Participants | 87 | 14 |
| Median (95% Confidence Interval) [Months] |
NA
|
21.7
|
| Title | Time to Disease Progression (TTP) |
|---|---|
| Description | 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. |
| Time Frame | Approximately 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 Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) |
|---|---|---|
| Arm/Group Description | Induction 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 Participants | 87 | 14 |
| Median (95% Confidence Interval) [Months] |
NA
|
13.31
|
| Title | Overall Survival (OS) |
|---|---|
| Description | Overall survival (OS) was measured from the date of first dose (start of induction) to the date of death due to any cause. |
| Time Frame | Up 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 Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) |
|---|---|---|
| Arm/Group Description | Induction 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 Participants | 87 | 14 |
| Median (95% Confidence Interval) [Months] |
NA
|
NA
|
| Title | Percentage of Participants With Treatment Emergent-Adverse Event |
|---|---|
| Description | 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. |
| Time Frame | Up 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 Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) |
|---|---|---|
| Arm/Group Description | Induction 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 Participants | 86 | 14 |
| Number [Percentage of participants] |
100.0
116.3%
|
100.0
714.3%
|
Adverse Events
| Time Frame | Up 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 Title | Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) | ||
| Arm/Group Description | Induction 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/86 (10.5%) | 7/14 (50%) | ||
Serious Adverse Events |
||||
| Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 28/86 (32.6%) | 5/14 (35.7%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile Neutropenia | 1/86 (1.2%) | 0/14 (0%) | ||
| Cardiac disorders | ||||
| Atrial Fibrillation | 4/86 (4.7%) | 0/14 (0%) | ||
| Atrial Flutter | 1/86 (1.2%) | 0/14 (0%) | ||
| Gastrointestinal disorders | ||||
| Haemorrhoidal Haemorrhage | 0/86 (0%) | 1/14 (7.1%) | ||
| Vomiting | 1/86 (1.2%) | 0/14 (0%) | ||
| General disorders | ||||
| Fatigue | 1/86 (1.2%) | 0/14 (0%) | ||
| Non-Cardiac Chest Pain | 2/86 (2.3%) | 0/14 (0%) | ||
| Pyrexia | 2/86 (2.3%) | 0/14 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis Acute | 1/86 (1.2%) | 0/14 (0%) | ||
| Infections and infestations | ||||
| Bacteraemia | 1/86 (1.2%) | 0/14 (0%) | ||
| Bacterial Sepsis | 1/86 (1.2%) | 0/14 (0%) | ||
| Bronchitis | 1/86 (1.2%) | 0/14 (0%) | ||
| Cellulitis | 1/86 (1.2%) | 0/14 (0%) | ||
| Diverticulitis | 1/86 (1.2%) | 0/14 (0%) | ||
| Herpes Zoster Disseminated | 1/86 (1.2%) | 0/14 (0%) | ||
| Influenza | 1/86 (1.2%) | 0/14 (0%) | ||
| Otitis Externa | 1/86 (1.2%) | 0/14 (0%) | ||
| Pneumonia | 2/86 (2.3%) | 2/14 (14.3%) | ||
| Pneumonia Parainfluenzae Viral | 1/86 (1.2%) | 0/14 (0%) | ||
| Pneumonia Streptococcal | 1/86 (1.2%) | 0/14 (0%) | ||
| Urinary Tract Infection | 1/86 (1.2%) | 0/14 (0%) | ||
| Viral Upper Respiratory Tract Infection | 1/86 (1.2%) | 0/14 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Femur Fracture | 1/86 (1.2%) | 0/14 (0%) | ||
| Hip Fracture | 1/86 (1.2%) | 0/14 (0%) | ||
| Pelvic Fracture | 1/86 (1.2%) | 0/14 (0%) | ||
| Toxicity to Various Agents | 0/86 (0%) | 1/14 (7.1%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/86 (1.2%) | 0/14 (0%) | ||
| Hyperglycaemia | 1/86 (1.2%) | 0/14 (0%) | ||
| Hyponatraemia | 1/86 (1.2%) | 0/14 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back Pain | 1/86 (1.2%) | 0/14 (0%) | ||
| Bone Lesion | 1/86 (1.2%) | 0/14 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute Leukaemia | 1/86 (1.2%) | 0/14 (0%) | ||
| Nervous system disorders | ||||
| Syncope | 1/86 (1.2%) | 0/14 (0%) | ||
| Psychiatric disorders | ||||
| Mental Status Changes | 2/86 (2.3%) | 0/14 (0%) | ||
| Renal and urinary disorders | ||||
| Nephrotic Syndrome | 1/86 (1.2%) | 0/14 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute Respiratory Failure | 1/86 (1.2%) | 0/14 (0%) | ||
| Bronchiectasis | 0/86 (0%) | 1/14 (7.1%) | ||
| Chronic Obstructive Pulmonary Disease | 1/86 (1.2%) | 0/14 (0%) | ||
| Laryngeal Oedema | 1/86 (1.2%) | 0/14 (0%) | ||
| Pulmonary Embolism | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Vascular disorders | ||||
| Deep Vein Thrombosis | 1/86 (1.2%) | 0/14 (0%) | ||
| Hypotension | 1/86 (1.2%) | 0/14 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Newly Diagnosed Multiple Myeloma (NDMM) | Relapsed Multiple Myeloma (RMM) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 86/86 (100%) | 14/14 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 12/86 (14%) | 1/14 (7.1%) | ||
| Hyperleukocytosis | 0/86 (0%) | 1/14 (7.1%) | ||
| Increased Tendency to Bruise | 1/86 (1.2%) | 0/14 (0%) | ||
| Iron Deficiency Anaemia | 1/86 (1.2%) | 0/14 (0%) | ||
| Leukopenia | 8/86 (9.3%) | 2/14 (14.3%) | ||
| Lymphopenia | 3/86 (3.5%) | 0/14 (0%) | ||
| Neutropenia | 12/86 (14%) | 3/14 (21.4%) | ||
| Thrombocytopenia | 5/86 (5.8%) | 2/14 (14.3%) | ||
| Cardiac disorders | ||||
| Atrial Fibrillation | 4/86 (4.7%) | 0/14 (0%) | ||
| Atrial Flutter | 1/86 (1.2%) | 0/14 (0%) | ||
| Bradycardia | 1/86 (1.2%) | 0/14 (0%) | ||
| Cardiac Failure Congestive | 1/86 (1.2%) | 0/14 (0%) | ||
| Palpitations | 3/86 (3.5%) | 0/14 (0%) | ||
| Pericardial Effusion | 1/86 (1.2%) | 0/14 (0%) | ||
| Sinus Tachycardia | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Supraventricular Tachycardia | 1/86 (1.2%) | 0/14 (0%) | ||
| Tachycardia | 3/86 (3.5%) | 0/14 (0%) | ||
| Ventricular Extrasystoles | 1/86 (1.2%) | 0/14 (0%) | ||
| Ear and labyrinth disorders | ||||
| Deafness | 0/86 (0%) | 1/14 (7.1%) | ||
| Deafness Bilateral | 1/86 (1.2%) | 0/14 (0%) | ||
| Ear Congestion | 2/86 (2.3%) | 0/14 (0%) | ||
| Ear Discomfort | 2/86 (2.3%) | 0/14 (0%) | ||
| Ear Pain | 2/86 (2.3%) | 0/14 (0%) | ||
| Eustachian Tube Obstruction | 0/86 (0%) | 1/14 (7.1%) | ||
| Excessive Cerumen Production | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Hypoacusis | 1/86 (1.2%) | 0/14 (0%) | ||
| Middle Ear Inflammation | 1/86 (1.2%) | 0/14 (0%) | ||
| Tinnitus | 3/86 (3.5%) | 0/14 (0%) | ||
| Vertigo | 1/86 (1.2%) | 0/14 (0%) | ||
| Endocrine disorders | ||||
| Hypothyroidism | 1/86 (1.2%) | 0/14 (0%) | ||
| Eye disorders | ||||
| Cataract | 4/86 (4.7%) | 0/14 (0%) | ||
| Cataract Subcapsular | 1/86 (1.2%) | 0/14 (0%) | ||
| Chalazion | 2/86 (2.3%) | 0/14 (0%) | ||
| Diplopia | 1/86 (1.2%) | 0/14 (0%) | ||
| Dry Eye | 4/86 (4.7%) | 0/14 (0%) | ||
| Eye Discharge | 0/86 (0%) | 1/14 (7.1%) | ||
| Eye Irritation | 2/86 (2.3%) | 0/14 (0%) | ||
| Eye Pruritus | 1/86 (1.2%) | 0/14 (0%) | ||
| Eye Swelling | 1/86 (1.2%) | 0/14 (0%) | ||
| Lacrimation Increased | 4/86 (4.7%) | 2/14 (14.3%) | ||
| Ocular Hyperaemia | 1/86 (1.2%) | 0/14 (0%) | ||
| Periorbital Oedema | 2/86 (2.3%) | 0/14 (0%) | ||
| Photophobia | 2/86 (2.3%) | 0/14 (0%) | ||
| Retinal Haemorrhage | 1/86 (1.2%) | 0/14 (0%) | ||
| Swelling of Eyelid | 1/86 (1.2%) | 0/14 (0%) | ||
| Vision Blurred | 4/86 (4.7%) | 2/14 (14.3%) | ||
| Visual Impairment | 0/86 (0%) | 1/14 (7.1%) | ||
| Vitreous Floaters | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Gastrointestinal disorders | ||||
| Abdominal Discomfort | 1/86 (1.2%) | 0/14 (0%) | ||
| Abdominal Distension | 3/86 (3.5%) | 1/14 (7.1%) | ||
| Abdominal Pain | 8/86 (9.3%) | 4/14 (28.6%) | ||
| Abdominal Pain Lower | 3/86 (3.5%) | 0/14 (0%) | ||
| Abdominal Pain Upper | 5/86 (5.8%) | 0/14 (0%) | ||
| Anal Incontinence | 1/86 (1.2%) | 0/14 (0%) | ||
| Aphthous Ulcer | 1/86 (1.2%) | 0/14 (0%) | ||
| Constipation | 27/86 (31.4%) | 0/14 (0%) | ||
| Dental Caries | 1/86 (1.2%) | 0/14 (0%) | ||
| Dental Discomfort | 1/86 (1.2%) | 0/14 (0%) | ||
| Diarrhoea | 38/86 (44.2%) | 6/14 (42.9%) | ||
| Diverticulum | 0/86 (0%) | 1/14 (7.1%) | ||
| Dry Mouth | 6/86 (7%) | 1/14 (7.1%) | ||
| Dyspepsia | 10/86 (11.6%) | 2/14 (14.3%) | ||
| Dysphagia | 1/86 (1.2%) | 0/14 (0%) | ||
| Enteritis | 1/86 (1.2%) | 0/14 (0%) | ||
| Faeces Discoloured | 1/86 (1.2%) | 0/14 (0%) | ||
| Flatulence | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Gastritis | 1/86 (1.2%) | 0/14 (0%) | ||
| Gastrooesophageal Reflux Disease | 4/86 (4.7%) | 2/14 (14.3%) | ||
| Gingival Disorder | 1/86 (1.2%) | 0/14 (0%) | ||
| Haematochezia | 1/86 (1.2%) | 0/14 (0%) | ||
| Haemorrhoids | 0/86 (0%) | 1/14 (7.1%) | ||
| Hyperaesthesia Teeth | 1/86 (1.2%) | 0/14 (0%) | ||
| Incarcerated Inguinal Hernia | 1/86 (1.2%) | 0/14 (0%) | ||
| Irritable Bowel Syndrome | 1/86 (1.2%) | 0/14 (0%) | ||
| Mouth Ulceration | 0/86 (0%) | 1/14 (7.1%) | ||
| Nausea | 43/86 (50%) | 3/14 (21.4%) | ||
| Oesophageal Pain | 0/86 (0%) | 1/14 (7.1%) | ||
| Oesophagitis | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Oral Pain | 2/86 (2.3%) | 0/14 (0%) | ||
| Rectal Haemorrhage | 2/86 (2.3%) | 0/14 (0%) | ||
| Retching | 1/86 (1.2%) | 0/14 (0%) | ||
| Stomatitis | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Swollen Tongue | 1/86 (1.2%) | 0/14 (0%) | ||
| Toothache | 6/86 (7%) | 0/14 (0%) | ||
| Vomiting | 25/86 (29.1%) | 5/14 (35.7%) | ||
| Vomiting Projectile | 1/86 (1.2%) | 0/14 (0%) | ||
| General disorders | ||||
| Asthenia | 3/86 (3.5%) | 1/14 (7.1%) | ||
| Axillary Pain | 2/86 (2.3%) | 0/14 (0%) | ||
| Catheter Site Bruise | 1/86 (1.2%) | 0/14 (0%) | ||
| Catheter Site Erythema | 1/86 (1.2%) | 0/14 (0%) | ||
| Catheter Site Haemorrhage | 1/86 (1.2%) | 0/14 (0%) | ||
| Catheter Site Pain | 2/86 (2.3%) | 0/14 (0%) | ||
| Catheter Site Pruritus | 1/86 (1.2%) | 0/14 (0%) | ||
| Chest Discomfort | 6/86 (7%) | 2/14 (14.3%) | ||
| Chest Pain | 2/86 (2.3%) | 0/14 (0%) | ||
| Chills | 17/86 (19.8%) | 1/14 (7.1%) | ||
| Face Oedema | 2/86 (2.3%) | 0/14 (0%) | ||
| Fatigue | 58/86 (67.4%) | 7/14 (50%) | ||
| Feeling Cold | 2/86 (2.3%) | 0/14 (0%) | ||
| Feeling Hot | 0/86 (0%) | 1/14 (7.1%) | ||
| Feeling Jittery | 0/86 (0%) | 1/14 (7.1%) | ||
| Gait Disturbance | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Influenza Like Illness | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Infusion Site Extravasation | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Injection Site Erythema | 3/86 (3.5%) | 1/14 (7.1%) | ||
| Injection Site Pain | 1/86 (1.2%) | 0/14 (0%) | ||
| Injection Site Rash | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Injection Site Reaction | 4/86 (4.7%) | 0/14 (0%) | ||
| Localised Oedema | 1/86 (1.2%) | 0/14 (0%) | ||
| Malaise | 2/86 (2.3%) | 0/14 (0%) | ||
| Medical Device Discomfort | 1/86 (1.2%) | 0/14 (0%) | ||
| Non-Cardiac Chest Pain | 4/86 (4.7%) | 0/14 (0%) | ||
| Oedema | 1/86 (1.2%) | 0/14 (0%) | ||
| Oedema Peripheral | 21/86 (24.4%) | 1/14 (7.1%) | ||
| Pain | 6/86 (7%) | 2/14 (14.3%) | ||
| Peripheral Swelling | 1/86 (1.2%) | 2/14 (14.3%) | ||
| Pyrexia | 17/86 (19.8%) | 1/14 (7.1%) | ||
| Tenderness | 0/86 (0%) | 1/14 (7.1%) | ||
| Thirst | 1/86 (1.2%) | 0/14 (0%) | ||
| Xerosis | 1/86 (1.2%) | 0/14 (0%) | ||
| Hepatobiliary disorders | ||||
| Hyperbilirubinaemia | 2/86 (2.3%) | 0/14 (0%) | ||
| Immune system disorders | ||||
| Anaphylactic Reaction | 1/86 (1.2%) | 0/14 (0%) | ||
| Drug Hypersensitivity | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Hypersensitivity | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Hypogammaglobulinaemia | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Seasonal Allergy | 6/86 (7%) | 0/14 (0%) | ||
| Infections and infestations | ||||
| Acute Sinusitis | 1/86 (1.2%) | 0/14 (0%) | ||
| Arthritis Infective | 1/86 (1.2%) | 0/14 (0%) | ||
| Bronchiolitis | 0/86 (0%) | 1/14 (7.1%) | ||
| Bronchitis | 7/86 (8.1%) | 1/14 (7.1%) | ||
| Bronchitis Viral | 2/86 (2.3%) | 0/14 (0%) | ||
| Candida Infection | 3/86 (3.5%) | 0/14 (0%) | ||
| Cellulitis | 2/86 (2.3%) | 0/14 (0%) | ||
| Conjunctivitis | 6/86 (7%) | 0/14 (0%) | ||
| Cytomegalovirus Chorioretinitis | 1/86 (1.2%) | 0/14 (0%) | ||
| Device Related Infection | 2/86 (2.3%) | 0/14 (0%) | ||
| Diverticulitis | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Ear Infection | 1/86 (1.2%) | 0/14 (0%) | ||
| Eye Infection | 1/86 (1.2%) | 0/14 (0%) | ||
| Folliculitis | 2/86 (2.3%) | 0/14 (0%) | ||
| Fungal Skin Infection | 1/86 (1.2%) | 0/14 (0%) | ||
| Gastroenteritis Viral | 1/86 (1.2%) | 0/14 (0%) | ||
| Gingival Abscess | 1/86 (1.2%) | 0/14 (0%) | ||
| Herpes Zoster | 1/86 (1.2%) | 0/14 (0%) | ||
| Herpes Zoster Disseminated | 2/86 (2.3%) | 0/14 (0%) | ||
| Hordeolum | 11/86 (12.8%) | 0/14 (0%) | ||
| Infected Bite | 1/86 (1.2%) | 0/14 (0%) | ||
| Influenza | 6/86 (7%) | 0/14 (0%) | ||
| Localised Infection | 1/86 (1.2%) | 0/14 (0%) | ||
| Lower Respiratory Tract Infection | 1/86 (1.2%) | 0/14 (0%) | ||
| Nasopharyngitis | 11/86 (12.8%) | 5/14 (35.7%) | ||
| Oral Candidiasis | 1/86 (1.2%) | 0/14 (0%) | ||
| Oral Herpes | 1/86 (1.2%) | 0/14 (0%) | ||
| Otitis Media | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Pharyngitis | 1/86 (1.2%) | 0/14 (0%) | ||
| Pharyngitis Streptococcal | 1/86 (1.2%) | 0/14 (0%) | ||
| Pneumonia | 8/86 (9.3%) | 3/14 (21.4%) | ||
| Pseudomonal Bacteraemia | 0/86 (0%) | 1/14 (7.1%) | ||
| Rash Pustular | 1/86 (1.2%) | 0/14 (0%) | ||
| Respiratory Tract Infection | 1/86 (1.2%) | 0/14 (0%) | ||
| Rhinitis | 1/86 (1.2%) | 0/14 (0%) | ||
| Sinusitis | 7/86 (8.1%) | 4/14 (28.6%) | ||
| Skin Infection | 2/86 (2.3%) | 0/14 (0%) | ||
| Tinea Infection | 1/86 (1.2%) | 0/14 (0%) | ||
| Tooth Abscess | 1/86 (1.2%) | 0/14 (0%) | ||
| Upper Respiratory Tract Infection | 30/86 (34.9%) | 7/14 (50%) | ||
| Urinary Tract Infection | 7/86 (8.1%) | 0/14 (0%) | ||
| Viral Infection | 3/86 (3.5%) | 0/14 (0%) | ||
| Viral Upper Respiratory Tract Infection | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Wound Infection | 1/86 (1.2%) | 0/14 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Abdominal Wall Wound | 1/86 (1.2%) | 0/14 (0%) | ||
| Arthropod Bite | 0/86 (0%) | 1/14 (7.1%) | ||
| Bone Contusion | 1/86 (1.2%) | 0/14 (0%) | ||
| Bone Fragmentation | 1/86 (1.2%) | 0/14 (0%) | ||
| Cartilage Injury | 1/86 (1.2%) | 0/14 (0%) | ||
| Contusion | 4/86 (4.7%) | 1/14 (7.1%) | ||
| Eye Contusion | 0/86 (0%) | 1/14 (7.1%) | ||
| Eyelid Contusion | 0/86 (0%) | 1/14 (7.1%) | ||
| Fall | 10/86 (11.6%) | 1/14 (7.1%) | ||
| Foot Fracture | 1/86 (1.2%) | 0/14 (0%) | ||
| Lower Limb Fracture | 1/86 (1.2%) | 0/14 (0%) | ||
| Muscle Strain | 3/86 (3.5%) | 0/14 (0%) | ||
| Pelvic Fracture | 3/86 (3.5%) | 0/14 (0%) | ||
| Radiation Skin Injury | 1/86 (1.2%) | 0/14 (0%) | ||
| Rib Fracture | 2/86 (2.3%) | 0/14 (0%) | ||
| Sunburn | 1/86 (1.2%) | 0/14 (0%) | ||
| Thermal Burn | 1/86 (1.2%) | 0/14 (0%) | ||
| Tooth Fracture | 1/86 (1.2%) | 0/14 (0%) | ||
| Investigations | ||||
| Alanine Aminotransferase Increased | 5/86 (5.8%) | 0/14 (0%) | ||
| Aspartate Aminotransferase Increased | 6/86 (7%) | 0/14 (0%) | ||
| Blood Alkaline Phosphatase Increased | 2/86 (2.3%) | 0/14 (0%) | ||
| Blood Creatinine Increased | 5/86 (5.8%) | 1/14 (7.1%) | ||
| Blood Pressure Increased | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Breath Sounds Abnormal | 1/86 (1.2%) | 0/14 (0%) | ||
| Gamma-Glutamyltransferase Increased | 2/86 (2.3%) | 0/14 (0%) | ||
| Oxygen Saturation Decreased | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Prostatic Specific Antigen Increased | 1/86 (1.2%) | 0/14 (0%) | ||
| Weight Decreased | 7/86 (8.1%) | 0/14 (0%) | ||
| Weight Increased | 8/86 (9.3%) | 0/14 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 18/86 (20.9%) | 2/14 (14.3%) | ||
| Dehydration | 15/86 (17.4%) | 2/14 (14.3%) | ||
| Diabetes Mellitus | 1/86 (1.2%) | 0/14 (0%) | ||
| Fluid Overload | 2/86 (2.3%) | 0/14 (0%) | ||
| Fluid Retention | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Gout | 2/86 (2.3%) | 0/14 (0%) | ||
| Hyperglycaemia | 7/86 (8.1%) | 0/14 (0%) | ||
| Hyperkalaemia | 2/86 (2.3%) | 0/14 (0%) | ||
| Hyperuricaemia | 1/86 (1.2%) | 0/14 (0%) | ||
| Hypoalbuminaemia | 2/86 (2.3%) | 0/14 (0%) | ||
| Hypocalcaemia | 4/86 (4.7%) | 2/14 (14.3%) | ||
| Hypokalaemia | 19/86 (22.1%) | 1/14 (7.1%) | ||
| Hypomagnesaemia | 9/86 (10.5%) | 2/14 (14.3%) | ||
| Hyponatraemia | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Hypophosphataemia | 6/86 (7%) | 0/14 (0%) | ||
| Hypovolaemia | 1/86 (1.2%) | 0/14 (0%) | ||
| Increased Appetite | 1/86 (1.2%) | 0/14 (0%) | ||
| Iron Deficiency | 1/86 (1.2%) | 0/14 (0%) | ||
| Type 2 Diabetes Mellitus | 0/86 (0%) | 1/14 (7.1%) | ||
| Vitamin B12 Deficiency | 0/86 (0%) | 1/14 (7.1%) | ||
| Vitamin D Deficiency | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 21/86 (24.4%) | 3/14 (21.4%) | ||
| Arthritis | 0/86 (0%) | 1/14 (7.1%) | ||
| Back Pain | 27/86 (31.4%) | 6/14 (42.9%) | ||
| Bone Lesion | 1/86 (1.2%) | 0/14 (0%) | ||
| Bone Pain | 10/86 (11.6%) | 2/14 (14.3%) | ||
| Bursitis | 1/86 (1.2%) | 0/14 (0%) | ||
| Costochondritis | 1/86 (1.2%) | 0/14 (0%) | ||
| Exostosis | 0/86 (0%) | 1/14 (7.1%) | ||
| Extremity Contracture | 1/86 (1.2%) | 0/14 (0%) | ||
| Fibromyalgia | 1/86 (1.2%) | 0/14 (0%) | ||
| Flank Pain | 3/86 (3.5%) | 0/14 (0%) | ||
| Groin Pain | 1/86 (1.2%) | 0/14 (0%) | ||
| Jaw Disorder | 0/86 (0%) | 1/14 (7.1%) | ||
| Joint Range of Motion Decreased | 1/86 (1.2%) | 0/14 (0%) | ||
| Joint Stiffness | 2/86 (2.3%) | 0/14 (0%) | ||
| Joint Swelling | 5/86 (5.8%) | 1/14 (7.1%) | ||
| Limb Discomfort | 1/86 (1.2%) | 0/14 (0%) | ||
| Muscle Spasms | 8/86 (9.3%) | 1/14 (7.1%) | ||
| Muscle Tightness | 1/86 (1.2%) | 0/14 (0%) | ||
| Muscle Twitching | 1/86 (1.2%) | 0/14 (0%) | ||
| Muscular Weakness | 9/86 (10.5%) | 0/14 (0%) | ||
| Musculoskeletal Chest Pain | 9/86 (10.5%) | 3/14 (21.4%) | ||
| Musculoskeletal Pain | 12/86 (14%) | 3/14 (21.4%) | ||
| Musculoskeletal Stiffness | 3/86 (3.5%) | 0/14 (0%) | ||
| Myalgia | 8/86 (9.3%) | 4/14 (28.6%) | ||
| Myalgia Intercostal | 2/86 (2.3%) | 1/14 (7.1%) | ||
| Neck Pain | 6/86 (7%) | 1/14 (7.1%) | ||
| Osteoporosis | 1/86 (1.2%) | 0/14 (0%) | ||
| Pain in Extremity | 15/86 (17.4%) | 4/14 (28.6%) | ||
| Pain in Jaw | 3/86 (3.5%) | 0/14 (0%) | ||
| Pathological Fracture | 1/86 (1.2%) | 0/14 (0%) | ||
| Synovial Cyst | 0/86 (0%) | 1/14 (7.1%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Basal Cell Carcinoma | 2/86 (2.3%) | 2/14 (14.3%) | ||
| Bowen's Disease | 0/86 (0%) | 1/14 (7.1%) | ||
| Skin Papilloma | 0/86 (0%) | 1/14 (7.1%) | ||
| Squamous Cell Carcinoma of Skin | 1/86 (1.2%) | 0/14 (0%) | ||
| Urethral Cancer | 1/86 (1.2%) | 0/14 (0%) | ||
| Nervous system disorders | ||||
| Anosmia | 1/86 (1.2%) | 0/14 (0%) | ||
| Burning Sensation | 1/86 (1.2%) | 0/14 (0%) | ||
| Carpal Tunnel Syndrome | 2/86 (2.3%) | 0/14 (0%) | ||
| Cognitive Disorder | 1/86 (1.2%) | 0/14 (0%) | ||
| Dizziness | 16/86 (18.6%) | 1/14 (7.1%) | ||
| Dizziness Postural | 1/86 (1.2%) | 0/14 (0%) | ||
| Dysarthria | 1/86 (1.2%) | 0/14 (0%) | ||
| Dysgeusia | 11/86 (12.8%) | 2/14 (14.3%) | ||
| Headache | 24/86 (27.9%) | 3/14 (21.4%) | ||
| Hypoaesthesia | 3/86 (3.5%) | 0/14 (0%) | ||
| Lethargy | 0/86 (0%) | 1/14 (7.1%) | ||
| Memory Impairment | 1/86 (1.2%) | 0/14 (0%) | ||
| Mental Impairment | 1/86 (1.2%) | 0/14 (0%) | ||
| Muscle Spasticity | 0/86 (0%) | 1/14 (7.1%) | ||
| Neuralgia | 1/86 (1.2%) | 0/14 (0%) | ||
| Neuropathy Peripheral | 14/86 (16.3%) | 2/14 (14.3%) | ||
| Paraesthesia | 3/86 (3.5%) | 3/14 (21.4%) | ||
| Peripheral Motor Neuropathy | 3/86 (3.5%) | 0/14 (0%) | ||
| Peripheral Sensory Neuropathy | 20/86 (23.3%) | 3/14 (21.4%) | ||
| Peroneal Nerve Palsy | 0/86 (0%) | 1/14 (7.1%) | ||
| Restless Legs Syndrome | 3/86 (3.5%) | 0/14 (0%) | ||
| Seizure | 1/86 (1.2%) | 0/14 (0%) | ||
| Sinus Headache | 1/86 (1.2%) | 0/14 (0%) | ||
| Somnolence | 1/86 (1.2%) | 0/14 (0%) | ||
| Syncope | 1/86 (1.2%) | 0/14 (0%) | ||
| Taste Disorder | 2/86 (2.3%) | 0/14 (0%) | ||
| Tremor | 3/86 (3.5%) | 0/14 (0%) | ||
| Vith Nerve Disorder | 0/86 (0%) | 1/14 (7.1%) | ||
| Product Issues | ||||
| Device Malfunction | 1/86 (1.2%) | 0/14 (0%) | ||
| Psychiatric disorders | ||||
| Agitation | 2/86 (2.3%) | 0/14 (0%) | ||
| Anxiety | 9/86 (10.5%) | 0/14 (0%) | ||
| Confusional State | 4/86 (4.7%) | 0/14 (0%) | ||
| Depression | 10/86 (11.6%) | 1/14 (7.1%) | ||
| Emotional Disorder | 1/86 (1.2%) | 0/14 (0%) | ||
| Insomnia | 28/86 (32.6%) | 2/14 (14.3%) | ||
| Irritability | 3/86 (3.5%) | 0/14 (0%) | ||
| Mental Status Changes | 1/86 (1.2%) | 0/14 (0%) | ||
| Nightmare | 1/86 (1.2%) | 0/14 (0%) | ||
| Personality Change | 1/86 (1.2%) | 0/14 (0%) | ||
| Restlessness | 2/86 (2.3%) | 0/14 (0%) | ||
| Renal and urinary disorders | ||||
| Bladder Discomfort | 1/86 (1.2%) | 0/14 (0%) | ||
| Bladder Outlet Obstruction | 1/86 (1.2%) | 0/14 (0%) | ||
| Bladder Spasm | 1/86 (1.2%) | 0/14 (0%) | ||
| Dysuria | 6/86 (7%) | 1/14 (7.1%) | ||
| Haematuria | 2/86 (2.3%) | 0/14 (0%) | ||
| Micturition Urgency | 1/86 (1.2%) | 0/14 (0%) | ||
| Nephrolithiasis | 1/86 (1.2%) | 0/14 (0%) | ||
| Nephrotic Syndrome | 1/86 (1.2%) | 0/14 (0%) | ||
| Nocturia | 4/86 (4.7%) | 2/14 (14.3%) | ||
| Pollakiuria | 3/86 (3.5%) | 1/14 (7.1%) | ||
| Renal Failure | 1/86 (1.2%) | 0/14 (0%) | ||
| Renal Impairment | 3/86 (3.5%) | 0/14 (0%) | ||
| Urinary Hesitation | 1/86 (1.2%) | 0/14 (0%) | ||
| Urinary Incontinence | 2/86 (2.3%) | 0/14 (0%) | ||
| Urinary Retention | 2/86 (2.3%) | 0/14 (0%) | ||
| Urine Flow Decreased | 0/86 (0%) | 1/14 (7.1%) | ||
| Urogenital Fistula | 1/86 (1.2%) | 0/14 (0%) | ||
| Reproductive system and breast disorders | ||||
| Breast Calcifications | 1/86 (1.2%) | 0/14 (0%) | ||
| Breast Pain | 2/86 (2.3%) | 0/14 (0%) | ||
| Female Genital Tract Fistula | 1/86 (1.2%) | 0/14 (0%) | ||
| Genital Erythema | 1/86 (1.2%) | 0/14 (0%) | ||
| Gynaecomastia | 1/86 (1.2%) | 0/14 (0%) | ||
| Metrorrhagia | 1/86 (1.2%) | 0/14 (0%) | ||
| Nipple Pain | 1/86 (1.2%) | 0/14 (0%) | ||
| Pelvic Pain | 2/86 (2.3%) | 0/14 (0%) | ||
| Prostatitis | 1/86 (1.2%) | 0/14 (0%) | ||
| Vulvovaginal Dryness | 1/86 (1.2%) | 0/14 (0%) | ||
| Vulvovaginal Pruritus | 2/86 (2.3%) | 0/14 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Atelectasis | 1/86 (1.2%) | 0/14 (0%) | ||
| Bronchospasm | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Chronic Obstructive Pulmonary Disease | 1/86 (1.2%) | 0/14 (0%) | ||
| Cough | 42/86 (48.8%) | 6/14 (42.9%) | ||
| Dysphonia | 4/86 (4.7%) | 0/14 (0%) | ||
| Dyspnoea | 27/86 (31.4%) | 3/14 (21.4%) | ||
| Dyspnoea Exertional | 1/86 (1.2%) | 0/14 (0%) | ||
| Epistaxis | 5/86 (5.8%) | 1/14 (7.1%) | ||
| Haemoptysis | 1/86 (1.2%) | 0/14 (0%) | ||
| Hiccups | 2/86 (2.3%) | 2/14 (14.3%) | ||
| Hypoxia | 3/86 (3.5%) | 0/14 (0%) | ||
| Laryngeal Inflammation | 1/86 (1.2%) | 0/14 (0%) | ||
| Laryngospasm | 1/86 (1.2%) | 0/14 (0%) | ||
| Lung Infiltration | 1/86 (1.2%) | 0/14 (0%) | ||
| Nasal Congestion | 11/86 (12.8%) | 3/14 (21.4%) | ||
| Nasal Dryness | 1/86 (1.2%) | 0/14 (0%) | ||
| Oropharyngeal Pain | 12/86 (14%) | 4/14 (28.6%) | ||
| Paranasal Sinus Discomfort | 2/86 (2.3%) | 0/14 (0%) | ||
| Paranasal Sinus Hypersecretion | 1/86 (1.2%) | 0/14 (0%) | ||
| Productive Cough | 8/86 (9.3%) | 4/14 (28.6%) | ||
| Pulmonary Embolism | 1/86 (1.2%) | 0/14 (0%) | ||
| Respiratory Distress | 0/86 (0%) | 1/14 (7.1%) | ||
| Respiratory Symptom | 1/86 (1.2%) | 0/14 (0%) | ||
| Respiratory Tract Congestion | 1/86 (1.2%) | 2/14 (14.3%) | ||
| Rhinitis Allergic | 10/86 (11.6%) | 0/14 (0%) | ||
| Rhinorrhoea | 1/86 (1.2%) | 2/14 (14.3%) | ||
| Rhonchi | 1/86 (1.2%) | 0/14 (0%) | ||
| Sinus Congestion | 5/86 (5.8%) | 2/14 (14.3%) | ||
| Sinus Disorder | 1/86 (1.2%) | 0/14 (0%) | ||
| Sinus Pain | 2/86 (2.3%) | 0/14 (0%) | ||
| Sleep Apnoea Syndrome | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Sneezing | 1/86 (1.2%) | 2/14 (14.3%) | ||
| Tachypnoea | 1/86 (1.2%) | 0/14 (0%) | ||
| Throat Irritation | 3/86 (3.5%) | 1/14 (7.1%) | ||
| Throat Tightness | 1/86 (1.2%) | 0/14 (0%) | ||
| Upper Respiratory Tract Congestion | 1/86 (1.2%) | 0/14 (0%) | ||
| Upper-Airway Cough Syndrome | 1/86 (1.2%) | 0/14 (0%) | ||
| Wheezing | 8/86 (9.3%) | 1/14 (7.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Actinic Keratosis | 1/86 (1.2%) | 0/14 (0%) | ||
| Alopecia | 6/86 (7%) | 1/14 (7.1%) | ||
| Chronic Pigmented Purpura | 1/86 (1.2%) | 0/14 (0%) | ||
| Cold Sweat | 1/86 (1.2%) | 0/14 (0%) | ||
| Decubitus Ulcer | 1/86 (1.2%) | 0/14 (0%) | ||
| Dermal Cyst | 0/86 (0%) | 1/14 (7.1%) | ||
| Dermatitis | 1/86 (1.2%) | 0/14 (0%) | ||
| Dermatitis Contact | 1/86 (1.2%) | 1/14 (7.1%) | ||
| Drug Eruption | 1/86 (1.2%) | 0/14 (0%) | ||
| Dry Skin | 3/86 (3.5%) | 1/14 (7.1%) | ||
| Eczema | 1/86 (1.2%) | 0/14 (0%) | ||
| Erythema | 2/86 (2.3%) | 0/14 (0%) | ||
| Hyperhidrosis | 5/86 (5.8%) | 1/14 (7.1%) | ||
| Nail Disorder | 0/86 (0%) | 1/14 (7.1%) | ||
| Nail Pigmentation | 1/86 (1.2%) | 0/14 (0%) | ||
| Night Sweats | 4/86 (4.7%) | 0/14 (0%) | ||
| Pain of Skin | 2/86 (2.3%) | 0/14 (0%) | ||
| Petechiae | 1/86 (1.2%) | 0/14 (0%) | ||
| Pruritus | 20/86 (23.3%) | 1/14 (7.1%) | ||
| Psoriasis | 1/86 (1.2%) | 0/14 (0%) | ||
| Rash | 12/86 (14%) | 1/14 (7.1%) | ||
| Rash Follicular | 1/86 (1.2%) | 0/14 (0%) | ||
| Rash Macular | 2/86 (2.3%) | 0/14 (0%) | ||
| Rash Maculo-Papular | 2/86 (2.3%) | 0/14 (0%) | ||
| Rash Pruritic | 1/86 (1.2%) | 0/14 (0%) | ||
| Scab | 1/86 (1.2%) | 0/14 (0%) | ||
| Skin Disorder | 1/86 (1.2%) | 0/14 (0%) | ||
| Skin Irritation | 1/86 (1.2%) | 0/14 (0%) | ||
| Skin Mass | 1/86 (1.2%) | 0/14 (0%) | ||
| Stasis Dermatitis | 1/86 (1.2%) | 0/14 (0%) | ||
| Urticaria | 4/86 (4.7%) | 0/14 (0%) | ||
| Social circumstances | ||||
| Menopause | 1/86 (1.2%) | 0/14 (0%) | ||
| Surgical and medical procedures | ||||
| Catheterisation Venous | 1/86 (1.2%) | 0/14 (0%) | ||
| Vascular disorders | ||||
| Deep Vein Thrombosis | 3/86 (3.5%) | 0/14 (0%) | ||
| Flushing | 12/86 (14%) | 1/14 (7.1%) | ||
| Haematoma | 1/86 (1.2%) | 0/14 (0%) | ||
| Hot Flush | 2/86 (2.3%) | 0/14 (0%) | ||
| Hypertension | 8/86 (9.3%) | 1/14 (7.1%) | ||
| Hypotension | 6/86 (7%) | 2/14 (14.3%) | ||
| Pallor | 1/86 (1.2%) | 0/14 (0%) | ||
| Varicose Vein | 1/86 (1.2%) | 0/14 (0%) | ||
| Venous Thrombosis | 1/86 (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/Title | Senior Director |
|---|---|
| Organization | Janssen Scientific Affairs |
| Phone | 844-434-4210 |
| ClinicalTrialDisclosure@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