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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03277105
• Collaborator: (none)
• Enrollment: 522
• Locations: 146
• Arms: 2
• Anticipated Duration (Months): 74
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to show that subcutaneous (SC) administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 (Dara SC) is non-inferior to intravenous (IV) administration of daratumumab (Dara IV) in terms of the overall response rate (ORR) and maximum trough concentration (Ctrough).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Dara SC; Drug: Dara IV	Phase 3

Detailed Description

The study population will consist of adults diagnosed with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD. The study consists of 3 phases: a screening phase (up to 28 days), a treatment phase, and a follow-up phase. Efficacy, pharmacokinetics, immunogenicity, biomarkers and safety will be assessed at scheduled time. Follow-up will continue until the end of the data collection period, approximately 24 months after the last participant was randomized or when the median overall survival for both arms has been reached, whichever occurs first. The primary hypotheses is that the ORR and maximum Ctrough for Dara SC 1800 milligram (mg) are not inferior to the ORR and maximum Ctrough, respectively, for Dara IV 16 mg per kilogram (mg/kg) in participants with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 522 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Multicenter Study of Subcutaneous vs. Intravenous Administration of Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma
• Actual Study Start Date: Oct 27, 2017
• Actual Primary Completion Date: Jun 27, 2019
• Anticipated Study Completion Date: Dec 26, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dara SC Participants will receive a fixed dose of daratumumab as 1800 milligram (mg) subcutaneously (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 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks.	Drug: Dara SC; Participants will receive a fixed dose of Dara SC as 1800 mg daratumumab with rHuPH20 2000 U/mL, once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.
Active Comparator: Dara IV Participants will receive daratumumab for intravenous infusion (Dara IV) 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks on Day 1 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks. For Participants still receiving treatment with Dara-IV at the time of Protocol Amendment 4 the duration of infusion may be shortened to a 90-minute infusion or participants will have the option to switch to Dara 1800 mg subcutaneous (SC) on Day 1 of any cycle, at the discretion of the investigator.	Drug: Dara SC; Participants will receive a fixed dose of Dara SC as 1800 mg daratumumab with rHuPH20 2000 U/mL, once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.; Drug: Dara IV; Participants will receive Dara IV 16 mg/kg once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.; Other Names: JNJ-54767414

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [Up to 2 years]

   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.

2. Maximum Trough Concentration (Ctrough) of Daratumumab [Predose on Cycle 3 Day 1 (each cycle of 28 days)]

   Maximum Ctrough was defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.

Secondary Outcome Measures

1. Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR) [Up to 2 years]

   Percentage of participants with treatment-emergent infusion-related reactions were reported.

2. Progression Free Survival (PFS) [Up to 2 years]

   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.

3. Percentage of Participants With Very Good Partial Response (VGPR) or Better [Up to 2 years]

   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.

4. Percentage of Participants With Complete Response (Including sCR) or Better [Up to 2 years]

   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.

5. Time to Next Therapy [Up to 2 years]

   Time to next therapy was defined as the time from randomization to the start of the first subsequent anti-cancer therapy.

6. Overall Survival (OS) [Up to 2 years]

   OS was defined as the time from the date of randomization to the date of the participant's death due to any cause.

7. Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ) [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)]

   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.

8. Duration of Response [Up to 2 years]

   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.

9. Time to Partial Response (PR) or Better [Up to 2 years]

   Time to PR or better was defined as the time from randomization until onset of first response of PR or better.

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

    Time to VGPR or better was defined as the time from randomization until onset of first VGPR or better.

11. Time to Complete Response (CR) or Better [Up to 2 years]

    Time to CR or better was defined as the time from randomization until onset of first CR or better.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Evidence of a response (Partial response [PR] or better based on investigator's determination of response by international myeloma working group [IMWG] criteria) to at least 1 prior treatment regimen

• Received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to [>=] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during the course of treatment (except for participants who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram/day [mg/day] for 4 days) would not be considered prior lines of therapy

• Documented multiple myeloma as defined by the criteria below:

1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria

2. Measurable disease at Screening as defined by any of the following:

3. Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein level >=200 mg/24 hours; or

4. Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio

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

• Meet the clinical laboratory criteria as specified in the protocol

• Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization

Exclusion Criteria:

• Received daratumumab or other anti-CD38 therapies previously

• Received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) before treatment

• Received autologous stem cell transplant within 12 weeks before the date of randomization, or the participant has previously received allogeneic stem cell transplant (regardless of timing)

• Plans to undergo a stem cell transplant prior to progression of disease on this study (these participants should not be enrolled to reduce disease burden prior to transplant)

• History of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease. Further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215-5418
2	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
3	Royal Prince Alfred Hospital	Camperdown		Australia	2050
4	St. Vincent's Hospital Melbourne	Fitzroy		Australia	3065
5	Alfred Health	Melbourne		Australia	3004
6	Fiona Stanley Hospital	Murdoch		Australia	6150
7	Sir Charles Gairdner Hospital	Nedlands		Australia	6009
8	Calvary Mater Newcastle Hospital	Waratah		Australia	2298
9	The Queen Elizabeth Hospital	Woodville South		Australia	5011
10	Princess Alexandra Hospital	Woolloongabba		Australia	4102
11	Hospital Do Cancer De Barretos - Fundacao Pio Xii	Barretos		Brazil	14784-400
12	Centro de Pesquisas Oncológicas - CEPON	Florianópolis		Brazil	88034-000
13	Hospital Amaral Carvalho - Centro de Ensino e Pesquisa	Jaú		Brazil	17210-070
14	Instituto Joinvilensse de Hematologia e Oncologia	Joinville		Brazil	89201-260
15	Centro de Pesquisa do Instituto do Câncer- Hospital São Vicente de Paulo	Passo Fundo		Brazil	99010-090
16	Hospital de Clínicas de Porto Alegre	Porto Alegre		Brazil	90035-903
17	Instituto COI de Pesquisa, Educacao e Gestao	Rio de Janeiro		Brazil	22793-080
18	CEHON	Salvador		Brazil	45995-000
19	Hospital de Base de São José do Rio Preto	São José do Rio Preto		Brazil	15090-000
20	Clinica Sao Germano	São Paulo		Brazil	01455-010
21	HCFMUSP	São Paulo		Brazil	05403-010
22	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
23	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
24	The Gordon & Leslie Diamond Health Care Center	Vancouver	British Columbia	Canada	V5Z 1M9
25	QEII Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 1V7
26	Victoria Hospital	London	Ontario	Canada	N6A 5W9
27	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 1X6
28	CHU de Québec -L'Hôtel-Dieu de Québec	Québec	Quebec	Canada	G1R 2J6
29	Fakultni nemocnice Brno	Brno		Czechia	625 00
30	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czechia	500 05
31	Fakultní nemocnice Olomouc	Olomouc		Czechia	779 00
32	Fakultni nemocnice Ostrava	Ostrava		Czechia	70852
33	Fakultni nemocnice Plzen, Hemato-onkologicke oddeleni	Plzen		Czechia	323 00
34	Fakultni nemocnice Kralovske Vinohrady	Praha 10		Czechia	100 34
35	Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie	Praha 2		Czechia	128 08
36	CHU Caen - Côte de Nacre	Caen		France	14033
37	Hopital Claude Huriez	Lille Cedex		France	59000
38	CHU de Nantes hôtel-Dieu	Nantes Cedex 1		France	44093
39	CHU de Boreaux	Pessac		France	33604
40	Centre hospitalier Lyon-Sud	Pierre-Bénite		France	69495
41	CHU Poitiers - Hôpital la Milétrie	Poitiers		France	86021
42	CHU Nancy Brabois	Vandoeuvre Les Nancy		France	54511
43	Alexandra General Hospital of Athens	Athens Attica		Greece	115 28
44	Hillel Yaffe Medical Center - Oncology	Hadera		Israel	38100
45	Rambam Med.Center - Hematology Institute	Haifa		Israel	31096
46	Carmel Medical Center	Haifa		Israel	3436212
47	Hadassah Medical Center	Jerusalem		Israel	91120
48	Rabin Medical Center, Beilinson Campus	Petah Tikva		Israel	49100
49	Sheba Medical Center Tel Hashomer	Ramat Gan		Israel	52621
50	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
51	Policlinico Sant'Orsola Malpighi	Bologna		Italy	40138
52	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy	20133
53	Ospedale Villa Sofia-Cervello	Palermo		Italy	90146
54	Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100
55	Azienda USL di Piacenza	Piacenza		Italy	29121
56	Università di Roma La Sapienza	Roma		Italy	00161
57	Policlinico Universitario Agostino Gemelli	Roma		Italy	00168
58	A.O.U. Città della Salute e della Scienza	Torino		Italy	10126
59	Fukuoka University Hospital	Fukuoka		Japan	814-0180
60	Chugoku Central Hospital	Fukuyama		Japan	720-0001
61	Ogaki Municipal Hospital	Gifu		Japan	503-8502
62	Gunma University Hospital	Gunma		Japan	371-0034
63	Kobe City Medical Center General Hospital	Hyogo		Japan	650-0047
64	Iwate Medical University Hospital	Iwate		Japan	020-8505
65	University Hospital Kyoto Perfectural University of Medicine	Kyoto		Japan	602-8566
66	Matsuyama Red Cross Hospital	Matsuyama		Japan	790-8524
67	Japanese Red Cross Nagoya Daini Hospital	Nagoya		Japan	466-8650
68	Nagoya City University Hospital	Nagoya		Japan	467-8602
69	Niigata Cancer Center Hospital	Niigata		Japan	951-8566
70	National Hospital Organization Okayama Medical Center	Okayama		Japan	701-1192
71	Osaka University Hospital	Osaka		Japan	565-0871
72	National Hospital Organization Sendai Medical Center	Sendai-City		Japan	983-8520
73	National Hospital Organization Shibukawa Medical Center	Shibukawa		Japan	377-0280
74	Japanese Red Cross Medical Center	Shibuya		Japan	150-8935
75	Pusan National University Hospital	Busan		Korea, Republic of	49241
76	National Cancer Center	Goyang-Si		Korea, Republic of	10408
77	Gachon University Gil Medical Center	Incheon		Korea, Republic of	21565
78	Severance Hospital	Seoul		Korea, Republic of	03722
79	Asan Medical Center	Seoul		Korea, Republic of	05505
80	Samsung Medical Center	Seoul		Korea, Republic of	06351
81	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
82	Ulsan University Hospital	Ulsan		Korea, Republic of	44033
83	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza	Brzozow		Poland	36-200
84	Szpital Uniwersytecki nr 2 im. Jana Biziela w Bydgoszczy	Bydgoszcz		Poland	85-168
85	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich	Chorzów		Poland	41-500
86	Szpitale Pomorskie Sp. z o.o.	Gdynia		Poland	81-519
87	Szpital Uniwersytecki w Krakowie	Krakow		Poland	31-501
88	Wojewodzki Szpital Specjalistyczny w Legnicy	Legnica		Poland	59-220
89	Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie	Lublin		Poland	20-081
90	Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego	Poznan		Poland	60-569
91	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy	Warszawa		Poland	02-781
92	Emergency Hospital of Dzerzhinsk	Dzerzhinsk		Russian Federation	606019
93	Ekaterinburg City Clinical Hospital # 7	Ekaterinburg		Russian Federation	620137
94	S.P. Botkin Moscow City Clinical Hospital	Moscow		Russian Federation	125284
95	City Clinical Hospital # 40	Moscow		Russian Federation	129301
96	Nizhniy Novgorod Region Clinical Hospital	Nizny Novgorod		Russian Federation	603126
97	Penza Regional Oncology Dispensary	Penza		Russian Federation	440071
98	Ryazan Regional Clinical Hospital	Ryazan		Russian Federation	390039
99	Saint Petersburg City Hospital #15	Saint-Petersburg		Russian Federation	123182
100	Samara Region Clinical Hospital	Samara		Russian Federation	443095
101	Clinical Research Institute of Hematology and Transfusiology	St-Petersburg		Russian Federation	191024
102	Oncology Dispensary of Komi Republic	Syktyvkar		Russian Federation	167904
103	Hosp. Univ. Germans Trias I Pujol	Badalona		Spain	08916
104	Hosp. Clinic I Provincial de Barcelona	Barcelona		Spain	08036
105	Hosp. Univ. Dr. Josep Trueta	Girona		Spain	17007
106	Hosp. Univ. Virgen de Las Nieves	Granada		Spain	18014
107	Hosp. Univ. de Canarias	La Laguna		Spain	38320
108	Hosp. de Leon	Leon		Spain	24080
109	Hosp. Gral. Univ. Gregorio Marañon	Madrid		Spain	28007
110	Hosp. Univ. Infanta Leonor	Madrid		Spain	28031
111	Hosp. Univ. 12 de Octubre	Madrid		Spain	28041
112	Clinica Univ. de Navarra	Pamplona		Spain	31008
113	Hosp. Quiron Madrid Pozuelo	Pozuelo de Alarcon		Spain	28223
114	Hosp. Clinico Univ. de Salamanca	Salamanca		Spain	37007
115	Hosp. Univ. Dr. Peset	Valencia		Spain	46017
116	Falu Lasarett	Falun		Sweden	79182
117	Helsingborgs lasarett	Helsingborg		Sweden	25187
118	Karolinska University Hospital, Huddinge	Huddinge		Sweden	141 86
119	Skanes universitetssjukhus	Lund		Sweden	222 41
120	Norrlands University Hospital	Umea		Sweden	907 46
121	Akademiska Sjukhuset	Uppsala		Sweden	SE-751 85
122	Chang-Hua Christian Hospital	Changhua		Taiwan	50006
123	China Medical University Hospital	Taichung City		Taiwan	40447
124	Taichung Veterans General Hospital	Taichung,		Taiwan	40705
125	National Cheng Kung University Hospital	Tainan		Taiwan	704
126	National Taiwan University Hospital	Taipei		Taiwan	10048
127	Chang Gung Memorial Hospital	Taoyuan		Taiwan	33305
128	Communal Nonprofit Enterprise 'Cherkasy Regional Oncology Dispensary Of Cherkasy Regional Council'	Cherkasy		Ukraine	18009
129	Dnepropetrovsk City Clinical Hospital #4, Regional Hematology Center	Dnepropetrovsk		Ukraine	49102
130	Ivano-Frankivsk Regional Clinical Hospital	Ivano-Frankivsk		Ukraine	76008
131	SI Grigoriev Institute for Medical Radiology National Academy of Medical Science of Ukraine	Kharkiv		Ukraine	61024
132	National Cancer Institute, Dept. of chemotherapy of hemoblastosis	Kiev		Ukraine	03022
133	Kiev Marrow Transplantation Center, Bone Marrow Transplantation Department	Kiev		Ukraine	03115
134	State Institution 'National Scientific Center for Radiation Medicine of NAMS of Ukraine'	Kiev		Ukraine	03115
135	Institute of Blood Pathology and Transfusion Medicine of AMS of Ukraine	Lviv		Ukraine	79044
136	Mykolaiv Regional Clinical Hospital	Mykolaiv		Ukraine	54000
137	Ukrainian Medical Stomatological Academy, Poltava Regional Clinical Hospital	Poltava		Ukraine	36011
138	Blackpool Victoria Hospital	Blackpool		United Kingdom	FY3 8NR
139	Royal Bournemouth Hospital	Bournemouth		United Kingdom	BH7 7DW
140	Leicester Royal Infirmary - Haematology	Leicester		United Kingdom	LE1 5WW
141	St Bartholomew's Hospital	London		United Kingdom	EC1A 7BE
142	Guy's & St Thomas Hospital	London		United Kingdom	SE1 9RT
143	Christie Hospital NHS Trust	Manchester		United Kingdom	M20 9BX
144	Nottingham City Hospital	Nottingham		United Kingdom	NG5 1PB
145	Royal Marsden Hospital	Surrey		United Kingdom	SM2 5PT
146	New Cross Hospital	Wolverhampton		United Kingdom	WV10 0QP

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Jan 21, 2020
• Statistical Analysis Plan - Feb 12, 2019

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT03277105
• Other Study ID Numbers: CR108342; 2017-000206-38; 54767414MMY3012
• First Posted: Sep 8, 2017
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell

Study Results

Participant Flow

Arm/Group Title	Daratumumab IV	Daratumumab SC
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

Baseline Characteristics

Arm/Group Title	Daratumumab IV	Daratumumab SC	Total
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 Participants	259	263	522
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.8 (10.16)	65.3 (9.11)	66.1 (9.66)
Sex: Female, Male (Count of Participants)
Female	110 42.5%	127 48.3%	237 45.4%
Male	149 57.5%	136 51.7%	285 54.6%
Ethnicity (NIH/OMB) (Count of 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%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	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%	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%
Unknown or Not Reported	12 4.6%	14 5.3%	26 5%
Region of Enrollment (Count of 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%	13 2.5%
ITALY	10 3.9%	16 6.1%	26 5%
JAPAN	24 9.3%	18 6.8%	42 8%
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%
SWEDEN	18 6.9%	18 6.8%	36 6.9%
TAIWAN	6 2.3%	8 3%	14 2.7%
UKRAINE	22 8.5%	25 9.5%	47 9%
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) (Count of 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%	155 29.7%
Data missing or Unknown	0 0%	1 0.4%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria, 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

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all the randomized participants.

Arm/Group Title	Daratumumab IV	Daratumumab SC
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.
Measure Participants	259	263
Number (95% Confidence Interval) [percentage of participants]	39.4 15.2%	43.3 16.5%

2. Primary Outcome

Title	Maximum Trough Concentration (Ctrough) of Daratumumab
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)

Outcome Measure Data

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
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.
Measure Participants	150	157
Mean (Standard Deviation) [micrograms per milliliter (mcg/mL)]	525 (227)	611 (318)

3. Secondary Outcome

Title	Percentage of Participants With Treatment-emergent Infusion-related Reactions (IRR)
Description	Percentage of participants with treatment-emergent infusion-related reactions were reported.
Time Frame	Up to 2 years

Outcome Measure Data

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
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.
Measure Participants	258	260
Number (95% Confidence Interval) [percentage of participants]	34.5 13.3%	12.7 4.8%

4. Secondary Outcome

Title	Progression Free Survival (PFS)
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

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all the randomized participants.

Arm/Group Title	Daratumumab IV	Daratumumab SC
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.
Measure Participants	259	263
Median (95% Confidence Interval) [months]	6.08	5.62

5. Secondary Outcome

Title	Percentage of Participants With Very Good Partial Response (VGPR) or Better
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

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all the randomized participants.

Arm/Group Title	Daratumumab IV	Daratumumab SC
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.
Measure Participants	259	263
Number (95% Confidence Interval) [percentage of participants]	20.8 8%	21.7 8.3%

6. Secondary Outcome

Title	Percentage of Participants With Complete Response (Including sCR) or Better
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

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all the randomized participants.

Arm/Group Title	Daratumumab IV	Daratumumab SC
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.
Measure Participants	259	263
Number (95% Confidence Interval) [percentage of participants]	4.6 1.8%	3.0 1.1%

7. Secondary Outcome

Title	Time to Next Therapy
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

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all the randomized participants.

Arm/Group Title	Daratumumab IV	Daratumumab SC
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.
Measure Participants	259	263
Median (95% Confidence Interval) [months]	9.30	8.80

8. Secondary Outcome

Title	Overall Survival (OS)
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

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all the randomized participants.

Arm/Group Title	Daratumumab IV	Daratumumab SC
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.
Measure Participants	259	263
Median (95% Confidence Interval) [months]	NA	NA

9. Secondary Outcome

Title	Patient-Reported Satisfaction With Therapy as Assessed With Cancer Therapy Satisfaction Questionnaire (CTSQ)
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)

Outcome Measure Data

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
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.
Measure Participants	259	263
Cycle 1 Day 8	70.5 (15.98)	76.9 (14.64)
Cycle 1 Day 15	72.1 (16.72)	78.8 (14.95)
Cycle 1 Day 22	72.8 (16.20)	78.7 (15.75)
Cycle 2 Day 1	74.2 (16.44)	79.7 (16.58)
Cycle 2 Day 8	74.8 (15.57)	80.1 (17.24)
Cycle 2 Day 15	74.3 (16.94)	80.0 (17.37)
Cycle 2 Day 22	75.2 (16.47)	79.3 (18.65)
Cycle 3 Day 1	76.0 (17.39)	80.4 (17.78)
Cycle 4 Day 1	76.6 (17.22)	79.5 (19.88)
Cycle 5 Day 1	77.1 (17.11)	79.6 (18.95)
Cycle 6 Day 1	76.1 (17.79)	81.9 (18.34)
Cycle 7 Day 1	78.6 (16.01)	85.0 (16.87)
Cycle 8 Day 1	79.2 (15.54)	85.0 (15.18)
Cycle 9 Day 1	79.8 (15.27)	85.2 (15.03)
Cycle 10 Day 1	79.4 (14.73)	85.8 (13.31)
Cycle 11 Day 1	79.1 (15.55)	84.8 (13.50)
Cycle 12 Day 1	80.3 (15.88)	85.4 (14.70)
Cycle 13 Day 1	79.6 (16.57)	84.4 (15.09)
Cycle 14 Day 1	80.6 (14.62)	83.5 (15.54)
Cycle 15 Day 1	80.2 (15.22)	86.2 (13.51)
Cycle 16 Day 1	79.4 (14.84)	88.5 (13.10)
Cycle 17 Day 1	79.0 (14.34)	90.9 (11.26)
Cycle 18 Day 1	84.8 (14.13)	91.4 (11.57)
Cycle 19 Day 1	92.9 (10.10)	89.3 (13.36)
Cycle 20 Day 1	86.6 (18.53)
Cycle 21 Day 1	84.5 (20.93)
Cycle 22 Day 1	96.4

10. Secondary Outcome

Title	Duration of Response
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

Outcome Measure Data

Analysis Population Description

Participants analyzed included responders (PR or better) in ITT analysis set.

Arm/Group Title	Daratumumab IV	Daratumumab SC
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.
Measure Participants	102	114
Median (95% Confidence Interval) [months]	10.64	11.17

11. Secondary Outcome

Title	Time to Partial Response (PR) or Better
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

Outcome Measure Data

Analysis Population Description

Participants analyzed included responders (PR or better) in ITT analysis set.

Arm/Group Title	Daratumumab IV	Daratumumab SC
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.
Measure Participants	102	114
Median (Full Range) [months]	1.02	1.02

12. Secondary Outcome

Title	Time to Very Good Partial Response (VGPR) or Better
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

Outcome Measure Data

Analysis Population Description

Participants analyzed included responders (VGPR or better) in ITT analysis set.

Arm/Group Title	Daratumumab IV	Daratumumab SC
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.
Measure Participants	54	57
Median (Full Range) [months]	1.91	1.94

13. Secondary Outcome

Title	Time to Complete Response (CR) or Better
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

Outcome Measure Data

Analysis Population Description

Participants analyzed included responders (CR or better) in ITT analysis set.

Arm/Group Title	Daratumumab IV	Daratumumab SC
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.
Measure Participants	12	8
Median (Full Range) [months]	6.42	7.39

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	77/258 (29.8%)		73/260 (28.1%)
Serious Adverse Events
	Daratumumab IV		Daratumumab SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/258 (29.5%)		68/260 (26.2%)
Blood and lymphatic system disorders
Anaemia	4/258 (1.6%)		5/260 (1.9%)
Disseminated Intravascular Coagulation	1/258 (0.4%)		0/260 (0%)
Febrile Neutropenia	2/258 (0.8%)		1/260 (0.4%)
Hyperviscosity Syndrome	0/258 (0%)		1/260 (0.4%)
Neutropenia	1/258 (0.4%)		0/260 (0%)
Thrombocytopenia	4/258 (1.6%)		3/260 (1.2%)
Cardiac disorders
Acute Coronary Syndrome	1/258 (0.4%)		0/260 (0%)
Angina Pectoris	1/258 (0.4%)		0/260 (0%)
Atrial Fibrillation	0/258 (0%)		1/260 (0.4%)
Atrioventricular Block Complete	1/258 (0.4%)		0/260 (0%)
Cardiac Failure	1/258 (0.4%)		1/260 (0.4%)
Cardiac Failure Chronic	0/258 (0%)		1/260 (0.4%)
Cardiopulmonary Failure	0/258 (0%)		1/260 (0.4%)
Myocardial Infarction	2/258 (0.8%)		0/260 (0%)
Tachycardia	0/258 (0%)		1/260 (0.4%)
Gastrointestinal disorders
Diarrhoea	1/258 (0.4%)		1/260 (0.4%)
Gastrointestinal Haemorrhage	1/258 (0.4%)		0/260 (0%)
Gingival Bleeding	0/258 (0%)		1/260 (0.4%)
Ileus	1/258 (0.4%)		0/260 (0%)
Inguinal Hernia	1/258 (0.4%)		0/260 (0%)
Nausea	2/258 (0.8%)		1/260 (0.4%)
Oesophageal Varices Haemorrhage	0/258 (0%)		1/260 (0.4%)
Small Intestinal Obstruction	0/258 (0%)		1/260 (0.4%)
Subileus	1/258 (0.4%)		0/260 (0%)
Vomiting	2/258 (0.8%)		0/260 (0%)
General disorders
Asthenia	0/258 (0%)		2/260 (0.8%)
Chest Discomfort	1/258 (0.4%)		0/260 (0%)
Chest Pain	0/258 (0%)		1/260 (0.4%)
Fatigue	2/258 (0.8%)		1/260 (0.4%)
General Physical Health Deterioration	5/258 (1.9%)		4/260 (1.5%)
Performance Status Decreased	0/258 (0%)		1/260 (0.4%)
Pyrexia	4/258 (1.6%)		4/260 (1.5%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/258 (0.4%)		0/260 (0%)
Infections and infestations
Bacteraemia	1/258 (0.4%)		0/260 (0%)
Bronchitis	1/258 (0.4%)		1/260 (0.4%)
Campylobacter Gastroenteritis	1/258 (0.4%)		0/260 (0%)
Furuncle	0/258 (0%)		1/260 (0.4%)
Hepatitis B Reactivation	1/258 (0.4%)		0/260 (0%)
Infection	1/258 (0.4%)		0/260 (0%)
Influenza	2/258 (0.8%)		3/260 (1.2%)
Listeriosis	0/258 (0%)		1/260 (0.4%)
Lower Respiratory Tract Infection	3/258 (1.2%)		3/260 (1.2%)
Lung Infection	2/258 (0.8%)		5/260 (1.9%)
Mastoiditis	1/258 (0.4%)		0/260 (0%)
Meningitis Cryptococcal	0/258 (0%)		1/260 (0.4%)
Meningitis Pneumococcal	1/258 (0.4%)		0/260 (0%)
Neutropenic Sepsis	0/258 (0%)		1/260 (0.4%)
Pneumocystis Jirovecii Pneumonia	2/258 (0.8%)		0/260 (0%)
Pneumonia	11/258 (4.3%)		7/260 (2.7%)
Respiratory Tract Infection	1/258 (0.4%)		2/260 (0.8%)
Sepsis	4/258 (1.6%)		3/260 (1.2%)
Septic Shock	4/258 (1.6%)		3/260 (1.2%)
Staphylococcal Sepsis	1/258 (0.4%)		0/260 (0%)
Upper Respiratory Tract Infection	1/258 (0.4%)		0/260 (0%)
Urinary Tract Infection	3/258 (1.2%)		0/260 (0%)
Injury, poisoning and procedural complications
Femoral Neck Fracture	0/258 (0%)		1/260 (0.4%)
Femur Fracture	2/258 (0.8%)		1/260 (0.4%)
Humerus Fracture	0/258 (0%)		2/260 (0.8%)
Upper Limb Fracture	0/258 (0%)		1/260 (0.4%)
Investigations
General Physical Condition Abnormal	0/258 (0%)		1/260 (0.4%)
Oxygen Saturation Decreased	0/258 (0%)		1/260 (0.4%)
Metabolism and nutrition disorders
Hypercalcaemia	4/258 (1.6%)		2/260 (0.8%)
Hyperglycaemia	2/258 (0.8%)		0/260 (0%)
Hypernatraemia	1/258 (0.4%)		0/260 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/258 (0%)		1/260 (0.4%)
Back Pain	1/258 (0.4%)		2/260 (0.8%)
Bone Pain	2/258 (0.8%)		5/260 (1.9%)
Muscular Weakness	1/258 (0.4%)		0/260 (0%)
Neck Pain	0/258 (0%)		1/260 (0.4%)
Pain in Extremity	0/258 (0%)		2/260 (0.8%)
Pathological Fracture	0/258 (0%)		1/260 (0.4%)
Spinal Pain	1/258 (0.4%)		0/260 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of Colon	1/258 (0.4%)		0/260 (0%)
Intestinal Adenocarcinoma	0/258 (0%)		1/260 (0.4%)
Plasmacytoma	1/258 (0.4%)		0/260 (0%)
Prostate Cancer Recurrent	0/258 (0%)		1/260 (0.4%)
Tumour Associated Fever	0/258 (0%)		1/260 (0.4%)
Nervous system disorders
Brain Oedema	1/258 (0.4%)		0/260 (0%)
Cerebral Infarction	0/258 (0%)		1/260 (0.4%)
Cerebrovascular Accident	0/258 (0%)		1/260 (0.4%)
Cerebrovascular Insufficiency	0/258 (0%)		1/260 (0.4%)
Monoparesis	1/258 (0.4%)		0/260 (0%)
Peripheral Sensory Neuropathy	1/258 (0.4%)		0/260 (0%)
Spinal Cord Compression	0/258 (0%)		1/260 (0.4%)
Syncope	0/258 (0%)		1/260 (0.4%)
Transient Ischaemic Attack	1/258 (0.4%)		1/260 (0.4%)
Psychiatric disorders
Confusional State	2/258 (0.8%)		0/260 (0%)
Renal and urinary disorders
Acute Kidney Injury	4/258 (1.6%)		4/260 (1.5%)
Haematuria	0/258 (0%)		2/260 (0.8%)
Myeloma Cast Nephropathy	0/258 (0%)		1/260 (0.4%)
Renal Failure	1/258 (0.4%)		2/260 (0.8%)
Reproductive system and breast disorders
Pelvic Pain	1/258 (0.4%)		0/260 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/258 (0.4%)		0/260 (0%)
Cough	0/258 (0%)		1/260 (0.4%)
Epistaxis	0/258 (0%)		1/260 (0.4%)
Hypoxia	1/258 (0.4%)		0/260 (0%)
Pulmonary Embolism	1/258 (0.4%)		0/260 (0%)
Pulmonary Thrombosis	1/258 (0.4%)		0/260 (0%)
Respiratory Distress	0/258 (0%)		1/260 (0.4%)
Respiratory Failure	0/258 (0%)		2/260 (0.8%)
Vascular disorders
Circulatory Collapse	1/258 (0.4%)		0/260 (0%)
Deep Vein Thrombosis	0/258 (0%)		1/260 (0.4%)
Hypertension	1/258 (0.4%)		1/260 (0.4%)
Hypotension	1/258 (0.4%)		0/260 (0%)
Other (Not Including Serious) Adverse Events
	Daratumumab IV		Daratumumab SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	204/258 (79.1%)		208/260 (80%)
Blood and lymphatic system disorders
Anaemia	58/258 (22.5%)		67/260 (25.8%)
Leukopenia	10/258 (3.9%)		18/260 (6.9%)
Lymphopenia	17/258 (6.6%)		19/260 (7.3%)
Neutropenia	34/258 (13.2%)		50/260 (19.2%)
Thrombocytopenia	48/258 (18.6%)		46/260 (17.7%)
Gastrointestinal disorders
Constipation	20/258 (7.8%)		14/260 (5.4%)
Diarrhoea	27/258 (10.5%)		39/260 (15%)
Nausea	26/258 (10.1%)		21/260 (8.1%)
Vomiting	18/258 (7%)		14/260 (5.4%)
General disorders
Asthenia	13/258 (5%)		12/260 (4.6%)
Chills	32/258 (12.4%)		15/260 (5.8%)
Fatigue	25/258 (9.7%)		28/260 (10.8%)
Oedema Peripheral	13/258 (5%)		9/260 (3.5%)
Pyrexia	30/258 (11.6%)		31/260 (11.9%)
Infections and infestations
Nasopharyngitis	16/258 (6.2%)		18/260 (6.9%)
Upper Respiratory Tract Infection	25/258 (9.7%)		35/260 (13.5%)
Metabolism and nutrition disorders
Hypokalaemia	15/258 (5.8%)		11/260 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	15/258 (5.8%)		19/260 (7.3%)
Back Pain	31/258 (12%)		27/260 (10.4%)
Bone Pain	8/258 (3.1%)		14/260 (5.4%)
Musculoskeletal Chest Pain	14/258 (5.4%)		16/260 (6.2%)
Pain in Extremity	11/258 (4.3%)		15/260 (5.8%)
Nervous system disorders
Headache	22/258 (8.5%)		13/260 (5%)
Psychiatric disorders
Insomnia	13/258 (5%)		14/260 (5.4%)
Respiratory, thoracic and mediastinal disorders
Cough	33/258 (12.8%)		22/260 (8.5%)
Dyspnoea	28/258 (10.9%)		14/260 (5.4%)
Nasal Congestion	13/258 (5%)		10/260 (3.8%)
Vascular disorders
Hypertension	22/258 (8.5%)		13/260 (5%)

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.