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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03277105




Registration number
NCT03277105
Ethics application status
Date submitted
7/09/2017
Date registered
8/09/2017
Date last updated
4/05/2020

Titles & IDs
Public title
A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma
Scientific title
A Phase 3 Randomized, Multicenter Study of Subcutaneous vs. Intravenous Administration of Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma
Secondary ID [1] 0 0
2017-000206-38
Secondary ID [2] 0 0
CR108342
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dara SC
Treatment: Drugs - Dara IV

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.

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.


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) - The ORR is defined as the proportion of participants who achieve 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 mg/24 hours, If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.
Timepoint [1] 0 0
At 6 months after 480 participants have been randomized (approximately 2 years)
Primary outcome [2] 0 0
Maximum Trough Concentration (Ctrough) of Daratumumab - Maximum Ctrough is defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.
Timepoint [2] 0 0
Cycle 3 (each cycle 28 days) Day 1
Secondary outcome [1] 0 0
Percentage of participants With Infusion-Related Reactions (IRR) - The Percentage of Participants with infusion reactions will be reported.
Timepoint [1] 0 0
At 6 months after 480 participants have been randomized (approximately 2 years)
Secondary outcome [2] 0 0
Progression-Free Survival (PFS) - PFS is defined as time from date of randomization to either progression of disease (PD), death due to any cause, whichever occurs first. IMWG criteria: Increase of 25% from lowest response value in any one of the following: Serum M component (absolute increase must be >=0.5 gram 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.
Timepoint [2] 0 0
At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years)
Secondary outcome [3] 0 0
Very Good Partial Response (VGPR) or Better Rate - The VGPR or better rate, defined as the proportion of participants achieving VGPR and complete response (CR) (including stringent complete response [sCR]), 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 greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein <100 milligram (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 free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescencea or 2- to 4 color flow cytometry.
Timepoint [3] 0 0
At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years)
Secondary outcome [4] 0 0
Complete Response (Including sCR) or Better Rate - As per IMWG criteria for CR is defined as 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.
Timepoint [4] 0 0
At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years)
Secondary outcome [5] 0 0
Time to Next Treatment - Time to next therapy is defined as the time from randomization to the start of the first subsequent anti-cancer therapy.
Timepoint [5] 0 0
At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years)
Secondary outcome [6] 0 0
Overall Survival (OS) - OS is defined as the time from the date of randomization to the date of the participant's death.
Timepoint [6] 0 0
At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years)
Secondary outcome [7] 0 0
Patient-Reported Satisfaction With Therapy - Patient-reported satisfaction with therapy is defined as the mean of responses to 7 of 9 questions in the modified cancer therapy satisfaction questionnaire (modified-CTSQ). Modified-CTSQ contain 9 items specific to satisfaction with therapy and for comparison of IV with SC administration. Satisfaction with therapy is calculated based on 7-items using 5-point verbal rating scale, 1, never; 5, always. Scores will be averaged and transformed to a 0-100 scale; higher scores represent better health.
Timepoint [7] 0 0
At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years)
Secondary outcome [8] 0 0
Duration of Response - Duration of response is as from initial date of first response to date of disease progression or death.
Timepoint [8] 0 0
At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years)
Secondary outcome [9] 0 0
Time to response - Time to response is defined as the time from randomization until onset of first response.
Timepoint [9] 0 0
At 6 months after 480 participants have been randomized (approximately 2 years) and 24 months after the last participant randomized (approximately 3 years)

Eligibility
Key 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:

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

2. 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
St. Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [3] 0 0
Alfred Health - Melbourne
Recruitment hospital [4] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [5] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [6] 0 0
Calvary Mater Newcastle Hospital - Waratah
Recruitment hospital [7] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [8] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment postcode(s) [6] 0 0
2298 - Waratah
Recruitment postcode(s) [7] 0 0
5011 - Woodville South
Recruitment postcode(s) [8] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
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United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
Brazil
State/province [3] 0 0
Barretos
Country [4] 0 0
Brazil
State/province [4] 0 0
Florianópolis
Country [5] 0 0
Brazil
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Jaú
Country [6] 0 0
Brazil
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Joinville
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Brazil
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Passo Fundo
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Brazil
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Porto Alegre
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Brazil
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Rio de Janeiro
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Brazil
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Salvador
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Brazil
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São José do Rio Preto
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Brazil
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São Paulo
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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Czechia
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Brno
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Czechia
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Hradec Kralove
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Czechia
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Olomouc
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Czechia
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Ostrava
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Czechia
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Plzen
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Czechia
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Praha 10
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Czechia
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Praha 2
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France
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Caen
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France
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Lille Cedex
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France
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Nantes Cedex 1
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France
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Pessac
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France
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Pierre-Bénite
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France
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Poitiers
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France
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Vandoeuvre Les Nancy
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Greece
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Athens Attica
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Israel
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Hadera
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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Bologna
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Italy
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Milano
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Italy
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Palermo
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Italy
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Pavia
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Italy
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Piacenza
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Italy
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Roma
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Italy
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Torino
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Japan
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Fukuoka
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Fukuyama
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Gifu
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Gunma
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Iwate
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Kobe-City,
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Kyoto
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Matsuyama
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Nagoya
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Niigata
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Okayama
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Osaka
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Sendai
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Japan
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Shibukawa
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Japan
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Shibuya
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Korea, Republic of
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Busan
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Korea, Republic of
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Goyang-Si
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Korea, Republic of
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Incheon
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Korea, Republic of
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Seoul
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Korea, Republic of
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Ulsan
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Poland
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Brzozow
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Poland
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Bydgoszcz
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Poland
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Chorzów
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Poland
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Gdynia
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Poland
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Krakow
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Poland
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Legnica
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Poland
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Lublin
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Poland
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Poznan
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Poland
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Warszawa
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Russian Federation
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Dzerzhinsk
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Russian Federation
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Ekaterinburg
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Russian Federation
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Moscow
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Russian Federation
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Nizny Novgorod
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Russian Federation
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Penza
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Russian Federation
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Ryazan
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Russian Federation
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Saint-Petersburg
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Russian Federation
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Samara
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Russian Federation
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St-Petersburg
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Russian Federation
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St. Petersburg
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Russian Federation
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Syktyvkar
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Spain
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Badalona
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Spain
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Barcelona
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Spain
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Girona
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Spain
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Granada
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Spain
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La Laguna
Country [91] 0 0
Spain
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Leon
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Spain
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Madrid
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Spain
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Pamplona
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Spain
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Pozuelo de Alarcon
Country [95] 0 0
Spain
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Salamanca
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Spain
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Valencia
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Sweden
State/province [97] 0 0
Falun
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Sweden
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Helsingborg
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Sweden
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Huddinge
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Sweden
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Lund
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Sweden
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Umea
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Sweden
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Uppsala
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Taiwan
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Changhua
Country [104] 0 0
Taiwan
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Taichung City
Country [105] 0 0
Taiwan
State/province [105] 0 0
Taichung,
Country [106] 0 0
Taiwan
State/province [106] 0 0
Tainan
Country [107] 0 0
Taiwan
State/province [107] 0 0
Taipei
Country [108] 0 0
Taiwan
State/province [108] 0 0
Taoyuan
Country [109] 0 0
Ukraine
State/province [109] 0 0
Cherkasy
Country [110] 0 0
Ukraine
State/province [110] 0 0
Dnepropetrovsk
Country [111] 0 0
Ukraine
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Ivano-Frankivsk
Country [112] 0 0
Ukraine
State/province [112] 0 0
Kharkiv
Country [113] 0 0
Ukraine
State/province [113] 0 0
Kiev
Country [114] 0 0
Ukraine
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Lviv
Country [115] 0 0
Ukraine
State/province [115] 0 0
Mykolaiv
Country [116] 0 0
Ukraine
State/province [116] 0 0
Poltava
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Blackpool
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Bournemouth
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Leicester
Country [120] 0 0
United Kingdom
State/province [120] 0 0
London
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Manchester
Country [122] 0 0
United Kingdom
State/province [122] 0 0
Nottingham
Country [123] 0 0
United Kingdom
State/province [123] 0 0
Surrey
Country [124] 0 0
United Kingdom
State/province [124] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT03277105
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications