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A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT03277105
Recruitment Status : Active, not recruiting
First Posted : September 8, 2017
Results First Posted : July 27, 2020
Last Update Posted : April 26, 2021
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: Dara SC
Drug: Dara IV
Enrollment 522
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days. Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Period Title: Overall Study
Started 259 263
Safety Analysis Set 258 260
Completed 0 0
Not Completed 259 263
Reason Not Completed
Death             77             73
Lost to Follow-up             0             3
Withdrawal by Subject             10             9
Other             1             3
Ongoing             171             175
Arm/Group Title Daratumumab IV Daratumumab SC Total
Hide Arm/Group Description Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days. Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days. Total of all reporting groups
Overall Number of Baseline Participants 259 263 522
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 259 participants 263 participants 522 participants
66.8  (10.16) 65.3  (9.11) 66.1  (9.66)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 259 participants 263 participants 522 participants
Female
110
  42.5%
127
  48.3%
237
  45.4%
Male
149
  57.5%
136
  51.7%
285
  54.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 259 participants 263 participants 522 participants
Hispanic or Latino
9
   3.5%
14
   5.3%
23
   4.4%
Not Hispanic or Latino
227
  87.6%
225
  85.6%
452
  86.6%
Unknown or Not Reported
23
   8.9%
24
   9.1%
47
   9.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 259 participants 263 participants 522 participants
American Indian or Alaska Native
0
   0.0%
1
   0.4%
1
   0.2%
Asian
40
  15.4%
32
  12.2%
72
  13.8%
Native Hawaiian or Other Pacific Islander
1
   0.4%
0
   0.0%
1
   0.2%
Black or African American
5
   1.9%
9
   3.4%
14
   2.7%
White
201
  77.6%
207
  78.7%
408
  78.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
12
   4.6%
14
   5.3%
26
   5.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 259 participants 263 participants 522 participants
AUSTRALIA
15
   5.8%
13
   4.9%
28
   5.4%
BRAZIL
10
   3.9%
15
   5.7%
25
   4.8%
CANADA
16
   6.2%
20
   7.6%
36
   6.9%
CZECH REPUBLIC
20
   7.7%
16
   6.1%
36
   6.9%
FRANCE
6
   2.3%
10
   3.8%
16
   3.1%
GREECE
1
   0.4%
6
   2.3%
7
   1.3%
ISRAEL
5
   1.9%
8
   3.0%
13
   2.5%
ITALY
10
   3.9%
16
   6.1%
26
   5.0%
JAPAN
24
   9.3%
18
   6.8%
42
   8.0%
POLAND
39
  15.1%
26
   9.9%
65
  12.5%
RUSSIAN FEDERATION
28
  10.8%
27
  10.3%
55
  10.5%
SOUTH KOREA
7
   2.7%
4
   1.5%
11
   2.1%
SPAIN
14
   5.4%
12
   4.6%
26
   5.0%
SWEDEN
18
   6.9%
18
   6.8%
36
   6.9%
TAIWAN
6
   2.3%
8
   3.0%
14
   2.7%
UKRAINE
22
   8.5%
25
   9.5%
47
   9.0%
UNITED KINGDOM
16
   6.2%
17
   6.5%
33
   6.3%
UNITED STATES
2
   0.8%
4
   1.5%
6
   1.1%
Stage of Disease (ISS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 259 participants 263 participants 522 participants
Stage I
94
  36.3%
82
  31.2%
176
  33.7%
Stage II
89
  34.4%
101
  38.4%
190
  36.4%
Stage III
76
  29.3%
79
  30.0%
155
  29.7%
Data missing or Unknown
0
   0.0%
1
   0.4%
1
   0.2%
[1]
Measure Description: The International Staging System (ISS) consists of following 3 stages - Stage I: serum beta2-microglobulin less than (<) 3.5 milligrams per liter (mg/L) and albumin greater than or equal to (>=) 3.5 grams (g) per 100 milliliter; Stage II: neither stage I nor stage III and Stage III: serum beta2-microglobulin >= 5.5 mg/L.
1.Primary Outcome
Title Overall Response Rate (ORR)
Hide Description ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria, during or after study treatment. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to less than (<) 200 milligram (mg)/24 hours, If the serum and urine M-proteins are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels were required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay was also not measurable, >=50% reduction in bone marrow plasma cells (PCs) was required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas was also required.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all the randomized participants.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 259 263
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
39.4
(33.4 to 45.6)
43.3
(37.3 to 49.6)
2.Primary Outcome
Title Maximum Trough Concentration (Ctrough) of Daratumumab
Hide Description Maximum Ctrough was defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.
Time Frame Predose on Cycle 3 Day 1 (each cycle of 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics (PK) population included participants who received at least 1 administration of study drug and had at least 1 pharmacokinetics sample concentration value after the first dose administration. Here, 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 150 157
Mean (Standard Deviation)
Unit of Measure: micrograms per milliliter (mcg/mL)
525  (227) 611  (318)
3.Secondary Outcome
Title Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR)
Hide Description Percentage of participants with treatment-emergent infusion-related reactions were reported.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 258 260
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
34.5
(28.7 to 40.6)
12.7
(8.9 to 17.4)
4.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS was defined as time from date of randomization to either progression of disease (PD), death due to any cause, whichever occurs first. IMWG criteria for PD: Increase of 25% from lowest response value in any one of the following: Serum M component (absolute increase must be >=0.5 grams per deciliter (g/dL), Urine M-component (absolute increase must be >=200 mg/24 hours), Participants without measurable serum and urine Mprotein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be >10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC% (absolute percentage must be >=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas and development of hypercalcemia (serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all the randomized participants.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 259 263
Median (95% Confidence Interval)
Unit of Measure: months
6.08
(4.73 to 7.43)
5.62
(4.70 to 7.49)
5.Secondary Outcome
Title Percentage of Participants With Very Good Partial Response (VGPR) or Better
Hide Description VGPR or better was defined as the percentage of participants who achieved VGPR or better (VGPR, complete response (CR) or stringent complete response [sCR]), based on computerized algorithm as per IMWG criteria during or after the study treatment. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or >=90 percent (%) reduction in serum M-protein plus urine M-protein <100 milligrams (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cellS (PCs) in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescencea or 2- to 4 color flow cytometry.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all the randomized participants.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 259 263
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
20.8
(16.1 to 26.3)
21.7
(16.8 to 27.1)
6.Secondary Outcome
Title Percentage of Participants With Complete Response (Including sCR) or Better
Hide Description CR or better was defined as percentage of participants with a CR or better (CR or stringent complete response [sCR]) based on computerized algorithm as per IMWG criteria. IMWG criteria for CR- negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by IHC, immunofluorescencea or 2- to 4 color flow cytometry.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all the randomized participants.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 259 263
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.6
(2.4 to 8.0)
3.0
(1.3 to 5.9)
7.Secondary Outcome
Title Time to Next Therapy
Hide Description Time to next therapy was defined as the time from randomization to the start of the first subsequent anti-cancer therapy.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all the randomized participants.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 259 263
Median (95% Confidence Interval)
Unit of Measure: months
9.30
(8.08 to 10.61)
8.80
(7.59 to 11.07)
8.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all the randomized participants.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 259 263
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(17.02 to NA)
NA [2] 
(NA to NA)
[1]
Median and upper limit of 95% CI were not estimable due to insufficient number of events.
[2]
Median and 95% CI were not estimable due to insufficient number of events.
9.Secondary Outcome
Title Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ)
Hide Description Modified-CTSQ contain 9 items (2 items for Thoughts about Cancer Therapy and 7 items in a defined domain of Satisfaction with Therapy) specific to satisfaction with therapy and for comparison of SC and IV administration. Satisfaction with therapy was calculated based on 7-items using 5-point verbal rating scale, where 1= never and 5= always. Scores were averaged and transformed to a 0-100 scale; higher scores represent better health. At least 5 of the 7 items within the Satisfaction with Therapy domain had to be completed to calculate a domain score. No domain score was calculated for Thoughts about Cancer Therapy.
Time Frame Cycle 1 (Days 8,15 and 22), Cycle 2 (Days 1,8,15 and 22), Cycle 3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21 and 22 (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all the randomized participants. Here, 'n' (number of participants analyzed) signifies the number of participants analyzed at a specified time point.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 259 263
Mean (Standard Deviation)
Unit of Measure: units on a scale
Cycle 1 Day 8 Number Analyzed 227 participants 230 participants
70.5  (15.98) 76.9  (14.64)
Cycle 1 Day 15 Number Analyzed 226 participants 238 participants
72.1  (16.72) 78.8  (14.95)
Cycle 1 Day 22 Number Analyzed 226 participants 239 participants
72.8  (16.20) 78.7  (15.75)
Cycle 2 Day 1 Number Analyzed 239 participants 238 participants
74.2  (16.44) 79.7  (16.58)
Cycle 2 Day 8 Number Analyzed 227 participants 232 participants
74.8  (15.57) 80.1  (17.24)
Cycle 2 Day 15 Number Analyzed 228 participants 224 participants
74.3  (16.94) 80.0  (17.37)
Cycle 2 Day 22 Number Analyzed 221 participants 214 participants
75.2  (16.47) 79.3  (18.65)
Cycle 3 Day 1 Number Analyzed 217 participants 224 participants
76.0  (17.39) 80.4  (17.78)
Cycle 4 Day 1 Number Analyzed 205 participants 209 participants
76.6  (17.22) 79.5  (19.88)
Cycle 5 Day 1 Number Analyzed 187 participants 188 participants
77.1  (17.11) 79.6  (18.95)
Cycle 6 Day 1 Number Analyzed 169 participants 159 participants
76.1  (17.79) 81.9  (18.34)
Cycle 7 Day 1 Number Analyzed 150 participants 137 participants
78.6  (16.01) 85.0  (16.87)
Cycle 8 Day 1 Number Analyzed 135 participants 127 participants
79.2  (15.54) 85.0  (15.18)
Cycle 9 Day 1 Number Analyzed 121 participants 113 participants
79.8  (15.27) 85.2  (15.03)
Cycle 10 Day 1 Number Analyzed 111 participants 103 participants
79.4  (14.73) 85.8  (13.31)
Cycle 11 Day 1 Number Analyzed 96 participants 94 participants
79.1  (15.55) 84.8  (13.50)
Cycle 12 Day 1 Number Analyzed 83 participants 81 participants
80.3  (15.88) 85.4  (14.70)
Cycle 13 Day 1 Number Analyzed 77 participants 76 participants
79.6  (16.57) 84.4  (15.09)
Cycle 14 Day 1 Number Analyzed 60 participants 61 participants
80.6  (14.62) 83.5  (15.54)
Cycle 15 Day 1 Number Analyzed 44 participants 40 participants
80.2  (15.22) 86.2  (13.51)
Cycle 16 Day 1 Number Analyzed 29 participants 29 participants
79.4  (14.84) 88.5  (13.10)
Cycle 17 Day 1 Number Analyzed 15 participants 20 participants
79.0  (14.34) 90.9  (11.26)
Cycle 18 Day 1 Number Analyzed 8 participants 10 participants
84.8  (14.13) 91.4  (11.57)
Cycle 19 Day 1 Number Analyzed 2 participants 8 participants
92.9  (10.10) 89.3  (13.36)
Cycle 20 Day 1 Number Analyzed 0 participants 4 participants
86.6  (18.53)
Cycle 21 Day 1 Number Analyzed 0 participants 3 participants
84.5  (20.93)
Cycle 22 Day 1 Number Analyzed 0 participants 1 participants
96.4
10.Secondary Outcome
Title Duration of Response
Hide Description Duration of response was defined as the duration from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria. PD was defined as an increase of 25 % from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >= 0.5 g/dL and >=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed included responders (PR or better) in ITT analysis set.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 102 114
Median (95% Confidence Interval)
Unit of Measure: months
10.64 [1] 
(9.26 to NA)
11.17 [1] 
(9.23 to NA)
[1]
Here NA signifies that upper limit of 95% CI was not estimable due to insufficient number of events.
11.Secondary Outcome
Title Time to Partial Response (PR) or Better
Hide Description Time to PR or better was defined as the time from randomization until onset of first response of PR or better.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed included responders (PR or better) in ITT analysis set.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 102 114
Median (Full Range)
Unit of Measure: months
1.02
(0.9 to 6.5)
1.02
(0.9 to 9.4)
12.Secondary Outcome
Title Time to Very Good Partial Response (VGPR) or Better
Hide Description Time to VGPR or better was defined as the time from randomization until onset of first VGPR or better.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed included responders (VGPR or better) in ITT analysis set.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 54 57
Median (Full Range)
Unit of Measure: months
1.91
(0.9 to 10.4)
1.94
(1.0 to 11.1)
13.Secondary Outcome
Title Time to Complete Response (CR) or Better
Hide Description Time to CR or better was defined as the time from randomization until onset of first CR or better.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed included responders (CR or better) in ITT analysis set.
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description:
Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
Overall Number of Participants Analyzed 12 8
Median (Full Range)
Unit of Measure: months
6.42
(1.1 to 14.9)
7.39
(1.2 to 11.2)
Time Frame Up to 2 years
Adverse Event Reporting Description Safety population included all randomized participants who received at least 1 dose of study drug.
 
Arm/Group Title Daratumumab IV Daratumumab SC
Hide Arm/Group Description Participants received daratumumab intravenous infusion (Dara IV) 16 milligrams per kilogram (mg/kg) once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days. Participants received daratumumab 1800 mg subcutaneous injection (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks thereafter until disease progression, unacceptable toxicity, withdrawal of consent, the investigator decides to stop treatment, or the start of subsequent anticancer therapy. The duration for each cycle was 28 days.
All-Cause Mortality
Daratumumab IV Daratumumab SC
Affected / at Risk (%) Affected / at Risk (%)
Total   77/258 (29.84%)   73/260 (28.08%) 
Hide Serious Adverse Events
Daratumumab IV Daratumumab SC
Affected / at Risk (%) Affected / at Risk (%)
Total   76/258 (29.46%)   68/260 (26.15%) 
Blood and lymphatic system disorders     
Anaemia * 1  4/258 (1.55%)  5/260 (1.92%) 
Disseminated Intravascular Coagulation * 1  1/258 (0.39%)  0/260 (0.00%) 
Febrile Neutropenia * 1  2/258 (0.78%)  1/260 (0.38%) 
Hyperviscosity Syndrome * 1  0/258 (0.00%)  1/260 (0.38%) 
Neutropenia * 1  1/258 (0.39%)  0/260 (0.00%) 
Thrombocytopenia * 1  4/258 (1.55%)  3/260 (1.15%) 
Cardiac disorders     
Acute Coronary Syndrome * 1  1/258 (0.39%)  0/260 (0.00%) 
Angina Pectoris * 1  1/258 (0.39%)  0/260 (0.00%) 
Atrial Fibrillation * 1  0/258 (0.00%)  1/260 (0.38%) 
Atrioventricular Block Complete * 1  1/258 (0.39%)  0/260 (0.00%) 
Cardiac Failure * 1  1/258 (0.39%)  1/260 (0.38%) 
Cardiac Failure Chronic * 1  0/258 (0.00%)  1/260 (0.38%) 
Cardiopulmonary Failure * 1  0/258 (0.00%)  1/260 (0.38%) 
Myocardial Infarction * 1  2/258 (0.78%)  0/260 (0.00%) 
Tachycardia * 1  0/258 (0.00%)  1/260 (0.38%) 
Gastrointestinal disorders     
Diarrhoea * 1  1/258 (0.39%)  1/260 (0.38%) 
Gastrointestinal Haemorrhage * 1  1/258 (0.39%)  0/260 (0.00%) 
Gingival Bleeding * 1  0/258 (0.00%)  1/260 (0.38%) 
Ileus * 1  1/258 (0.39%)  0/260 (0.00%) 
Inguinal Hernia * 1  1/258 (0.39%)  0/260 (0.00%) 
Nausea * 1  2/258 (0.78%)  1/260 (0.38%) 
Oesophageal Varices Haemorrhage * 1  0/258 (0.00%)  1/260 (0.38%) 
Small Intestinal Obstruction * 1  0/258 (0.00%)  1/260 (0.38%) 
Subileus * 1  1/258 (0.39%)  0/260 (0.00%) 
Vomiting * 1  2/258 (0.78%)  0/260 (0.00%) 
General disorders     
Asthenia * 1  0/258 (0.00%)  2/260 (0.77%) 
Chest Discomfort * 1  1/258 (0.39%)  0/260 (0.00%) 
Chest Pain * 1  0/258 (0.00%)  1/260 (0.38%) 
Fatigue * 1  2/258 (0.78%)  1/260 (0.38%) 
General Physical Health Deterioration * 1  5/258 (1.94%)  4/260 (1.54%) 
Performance Status Decreased * 1  0/258 (0.00%)  1/260 (0.38%) 
Pyrexia * 1  4/258 (1.55%)  4/260 (1.54%) 
Hepatobiliary disorders     
Hyperbilirubinaemia * 1  1/258 (0.39%)  0/260 (0.00%) 
Infections and infestations     
Bacteraemia * 1  1/258 (0.39%)  0/260 (0.00%) 
Bronchitis * 1  1/258 (0.39%)  1/260 (0.38%) 
Campylobacter Gastroenteritis * 1  1/258 (0.39%)  0/260 (0.00%) 
Furuncle * 1  0/258 (0.00%)  1/260 (0.38%) 
Hepatitis B Reactivation * 1  1/258 (0.39%)  0/260 (0.00%) 
Infection * 1  1/258 (0.39%)  0/260 (0.00%) 
Influenza * 1  2/258 (0.78%)  3/260 (1.15%) 
Listeriosis * 1  0/258 (0.00%)  1/260 (0.38%) 
Lower Respiratory Tract Infection * 1  3/258 (1.16%)  3/260 (1.15%) 
Lung Infection * 1  2/258 (0.78%)  5/260 (1.92%) 
Mastoiditis * 1  1/258 (0.39%)  0/260 (0.00%) 
Meningitis Cryptococcal * 1  0/258 (0.00%)  1/260 (0.38%) 
Meningitis Pneumococcal * 1  1/258 (0.39%)  0/260 (0.00%) 
Neutropenic Sepsis * 1  0/258 (0.00%)  1/260 (0.38%) 
Pneumocystis Jirovecii Pneumonia * 1  2/258 (0.78%)  0/260 (0.00%) 
Pneumonia * 1  11/258 (4.26%)  7/260 (2.69%) 
Respiratory Tract Infection * 1  1/258 (0.39%)  2/260 (0.77%) 
Sepsis * 1  4/258 (1.55%)  3/260 (1.15%) 
Septic Shock * 1  4/258 (1.55%)  3/260 (1.15%) 
Staphylococcal Sepsis * 1  1/258 (0.39%)  0/260 (0.00%) 
Upper Respiratory Tract Infection * 1  1/258 (0.39%)  0/260 (0.00%) 
Urinary Tract Infection * 1  3/258 (1.16%)  0/260 (0.00%) 
Injury, poisoning and procedural complications     
Femoral Neck Fracture * 1  0/258 (0.00%)  1/260 (0.38%) 
Femur Fracture * 1  2/258 (0.78%)  1/260 (0.38%) 
Humerus Fracture * 1  0/258 (0.00%)  2/260 (0.77%) 
Upper Limb Fracture * 1  0/258 (0.00%)  1/260 (0.38%) 
Investigations     
General Physical Condition Abnormal * 1  0/258 (0.00%)  1/260 (0.38%) 
Oxygen Saturation Decreased * 1  0/258 (0.00%)  1/260 (0.38%) 
Metabolism and nutrition disorders     
Hypercalcaemia * 1  4/258 (1.55%)  2/260 (0.77%) 
Hyperglycaemia * 1  2/258 (0.78%)  0/260 (0.00%) 
Hypernatraemia * 1  1/258 (0.39%)  0/260 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  0/258 (0.00%)  1/260 (0.38%) 
Back Pain * 1  1/258 (0.39%)  2/260 (0.77%) 
Bone Pain * 1  2/258 (0.78%)  5/260 (1.92%) 
Muscular Weakness * 1  1/258 (0.39%)  0/260 (0.00%) 
Neck Pain * 1  0/258 (0.00%)  1/260 (0.38%) 
Pain in Extremity * 1  0/258 (0.00%)  2/260 (0.77%) 
Pathological Fracture * 1  0/258 (0.00%)  1/260 (0.38%) 
Spinal Pain * 1  1/258 (0.39%)  0/260 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma of Colon * 1  1/258 (0.39%)  0/260 (0.00%) 
Intestinal Adenocarcinoma * 1  0/258 (0.00%)  1/260 (0.38%) 
Plasmacytoma * 1  1/258 (0.39%)  0/260 (0.00%) 
Prostate Cancer Recurrent * 1  0/258 (0.00%)  1/260 (0.38%) 
Tumour Associated Fever * 1  0/258 (0.00%)  1/260 (0.38%) 
Nervous system disorders     
Brain Oedema * 1  1/258 (0.39%)  0/260 (0.00%) 
Cerebral Infarction * 1  0/258 (0.00%)  1/260 (0.38%) 
Cerebrovascular Accident * 1  0/258 (0.00%)  1/260 (0.38%) 
Cerebrovascular Insufficiency * 1  0/258 (0.00%)  1/260 (0.38%) 
Monoparesis * 1  1/258 (0.39%)  0/260 (0.00%) 
Peripheral Sensory Neuropathy * 1  1/258 (0.39%)  0/260 (0.00%) 
Spinal Cord Compression * 1  0/258 (0.00%)  1/260 (0.38%) 
Syncope * 1  0/258 (0.00%)  1/260 (0.38%) 
Transient Ischaemic Attack * 1  1/258 (0.39%)  1/260 (0.38%) 
Psychiatric disorders     
Confusional State * 1  2/258 (0.78%)  0/260 (0.00%) 
Renal and urinary disorders     
Acute Kidney Injury * 1  4/258 (1.55%)  4/260 (1.54%) 
Haematuria * 1  0/258 (0.00%)  2/260 (0.77%) 
Myeloma Cast Nephropathy * 1  0/258 (0.00%)  1/260 (0.38%) 
Renal Failure * 1  1/258 (0.39%)  2/260 (0.77%) 
Reproductive system and breast disorders     
Pelvic Pain * 1  1/258 (0.39%)  0/260 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Bronchospasm * 1  1/258 (0.39%)  0/260 (0.00%) 
Cough * 1  0/258 (0.00%)  1/260 (0.38%) 
Epistaxis * 1  0/258 (0.00%)  1/260 (0.38%) 
Hypoxia * 1  1/258 (0.39%)  0/260 (0.00%) 
Pulmonary Embolism * 1  1/258 (0.39%)  0/260 (0.00%) 
Pulmonary Thrombosis * 1  1/258 (0.39%)  0/260 (0.00%) 
Respiratory Distress * 1  0/258 (0.00%)  1/260 (0.38%) 
Respiratory Failure * 1  0/258 (0.00%)  2/260 (0.77%) 
Vascular disorders     
Circulatory Collapse * 1  1/258 (0.39%)  0/260 (0.00%) 
Deep Vein Thrombosis * 1  0/258 (0.00%)  1/260 (0.38%) 
Hypertension * 1  1/258 (0.39%)  1/260 (0.38%) 
Hypotension * 1  1/258 (0.39%)  0/260 (0.00%) 
1
Term from vocabulary, MedDRA Version 21.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Daratumumab IV Daratumumab SC
Affected / at Risk (%) Affected / at Risk (%)
Total   204/258 (79.07%)   208/260 (80.00%) 
Blood and lymphatic system disorders     
Anaemia * 1  58/258 (22.48%)  67/260 (25.77%) 
Leukopenia * 1  10/258 (3.88%)  18/260 (6.92%) 
Lymphopenia * 1  17/258 (6.59%)  19/260 (7.31%) 
Neutropenia * 1  34/258 (13.18%)  50/260 (19.23%) 
Thrombocytopenia * 1  48/258 (18.60%)  46/260 (17.69%) 
Gastrointestinal disorders     
Constipation * 1  20/258 (7.75%)  14/260 (5.38%) 
Diarrhoea * 1  27/258 (10.47%)  39/260 (15.00%) 
Nausea * 1  26/258 (10.08%)  21/260 (8.08%) 
Vomiting * 1  18/258 (6.98%)  14/260 (5.38%) 
General disorders     
Asthenia * 1  13/258 (5.04%)  12/260 (4.62%) 
Chills * 1  32/258 (12.40%)  15/260 (5.77%) 
Fatigue * 1  25/258 (9.69%)  28/260 (10.77%) 
Oedema Peripheral * 1  13/258 (5.04%)  9/260 (3.46%) 
Pyrexia * 1  30/258 (11.63%)  31/260 (11.92%) 
Infections and infestations     
Nasopharyngitis * 1  16/258 (6.20%)  18/260 (6.92%) 
Upper Respiratory Tract Infection * 1  25/258 (9.69%)  35/260 (13.46%) 
Metabolism and nutrition disorders     
Hypokalaemia * 1  15/258 (5.81%)  11/260 (4.23%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  15/258 (5.81%)  19/260 (7.31%) 
Back Pain * 1  31/258 (12.02%)  27/260 (10.38%) 
Bone Pain * 1  8/258 (3.10%)  14/260 (5.38%) 
Musculoskeletal Chest Pain * 1  14/258 (5.43%)  16/260 (6.15%) 
Pain in Extremity * 1  11/258 (4.26%)  15/260 (5.77%) 
Nervous system disorders     
Headache * 1  22/258 (8.53%)  13/260 (5.00%) 
Psychiatric disorders     
Insomnia * 1  13/258 (5.04%)  14/260 (5.38%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  33/258 (12.79%)  22/260 (8.46%) 
Dyspnoea * 1  28/258 (10.85%)  14/260 (5.38%) 
Nasal Congestion * 1  13/258 (5.04%)  10/260 (3.85%) 
Vascular disorders     
Hypertension * 1  22/258 (8.53%)  13/260 (5.00%) 
1
Term from vocabulary, MedDRA Version 21.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Global Medical Head
Organization: Janssen Research & Development, LLC
Phone: 844-434-4210
EMail: ClinicalTrialDisclosure@its.jnj.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03277105    
Other Study ID Numbers: CR108342
2017-000206-38 ( EudraCT Number )
54767414MMY3012 ( Other Identifier: Janssen Research & Development, LLC )
First Submitted: September 7, 2017
First Posted: September 8, 2017
Results First Submitted: June 19, 2020
Results First Posted: July 27, 2020
Last Update Posted: April 26, 2021