Daratumumab (HuMax®-CD38) Safety Study in Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00574288

Recruitment Status : Completed

First Posted : December 17, 2007

Results First Posted : March 9, 2017

Last Update Posted : April 27, 2018

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Sponsor:

Information provided by (Responsible Party):

Janssen Research & Development, LLC

Study Type	Interventional
Study Design	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Multiple Myeloma
Interventions	Drug: Part 1: Daratumumab Drug: Part 2: Daratumumab Other: Methylprednisolone Other: Dexamethasone
Enrollment	104

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Part 1 - <4 mg/kg	Part 1 - 4 mg/kg	Part 1 - 8 mg/kg	Part 1 - 16 mg/kg	Part 1 - 24 mg/kg	Part 2 - 8 mg/kg	Part 2 - 16 mg/kg
Arm/Group Description	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...
Arm/Group Description	Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Period Title: Overall Study
Started	20	3	3	3	3	30	42
Completed	0	0	0	1	1	4	14
Not Completed	20	3	3	2	2	26	28
Reason Not Completed
Adverse Event	2	0	0	0	1	0	0
Death	0	0	0	0	0	25	21
Lost to Follow-up	0	0	0	0	0	1	2
Study Terminated By Sponsor	0	0	0	0	0	0	5
Progressive Disease	17	2	3	2	1	0	0
Other	1	1	0	0	0	0	0

Baseline Characteristics

Arm/Group Title		Part 1 - <4 mg/kg	Part 1 - 4 mg/kg	Part 1 - 8 mg/kg	Part 1 - 16 mg/kg	Part 1 - 24 mg/kg	Part 2 - 8 mg/kg	Part 2 - 16 mg/kg	Total
Arm/Group Description		Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Total of all reporting groups
Arm/Group Description		Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Total of all reporting groups
Overall Number of Baseline Participants		20	3	3	3	3	30	42	104
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	20 participants	3 participants	3 participants	3 participants	3 participants	30 participants	42 participants	104 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	11 55.0%	2 66.7%	2 66.7%	3 100.0%	2 66.7%	21 70.0%	22 52.4%	63 60.6%
	>=65 years	9 45.0%	1 33.3%	1 33.3%	0 0.0%	1 33.3%	9 30.0%	20 47.6%	41 39.4%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	20 participants	3 participants	3 participants	3 participants	3 participants	30 participants	42 participants	104 participants
		61.8 (9.24)	64 (2)	61.3 (6.11)	53 (1.73)	59 (9.54)	58.6 (10.05)	63.8 (8.27)	61.4 (9)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	20 participants	3 participants	3 participants	3 participants	3 participants	30 participants	42 participants	104 participants
	Female	7 35.0%	2 66.7%	0 0.0%	0 0.0%	0 0.0%	9 30.0%	15 35.7%	33 31.7%
	Male	13 65.0%	1 33.3%	3 100.0%	3 100.0%	3 100.0%	21 70.0%	27 64.3%	71 68.3%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	20 participants	3 participants	3 participants	3 participants	3 participants	30 participants	42 participants	104 participants
Denmark		11 55.0%	1 33.3%	2 66.7%	2 66.7%	0 0.0%	5 16.7%	9 21.4%	30 28.8%
Netherlands		4 20.0%	2 66.7%	1 33.3%	1 33.3%	2 66.7%	14 46.7%	8 19.0%	32 30.8%
Sweden		5 25.0%	0 0.0%	0 0.0%	0 0.0%	1 33.3%	5 16.7%	11 26.2%	22 21.2%
United States		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	6 20.0%	14 33.3%	20 19.2%
No. of Prior Lines of Therapy Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	20 participants	3 participants	3 participants	3 participants	3 participants	30 participants	42 participants	104 participants
	<= 3 Lines	2 10.0%	2 66.7%	0 0.0%	0 0.0%	0 0.0%	6 20.0%	16 38.1%	26 25.0%
	> 3 Lines	18 90.0%	1 33.3%	3 100.0%	3 100.0%	3 100.0%	24 80.0%	26 61.9%	78 75.0%
Refractory to proteasome inhibitor (PI)/immunomodulatory agent (IMiD) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	20 participants	3 participants	3 participants	3 participants	3 participants	30 participants	42 participants	104 participants
	Both a PI and IMiD	0 0.0%	2 66.7%	3 100.0%	1 33.3%	2 66.7%	19 63.3%	27 64.3%	54 51.9%
	PI only	0 0.0%	1 33.3%	0 0.0%	0 0.0%	0 0.0%	2 6.7%	3 7.1%	6 5.8%
	IMiD only	0 0.0%	0 0.0%	0 0.0%	1 33.3%	1 33.3%	6 20.0%	4 9.5%	12 11.5%
	None	20 100.0%	0 0.0%	0 0.0%	1 33.3%	0 0.0%	3 10.0%	8 19.0%	32 30.8%

Outcome Measures

1.Primary Outcome


Title	Number of Participants With Adverse Events
Description	An adverse event (AE) was any untoward medical occurrence in a partici...
Description	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame	Up to Week 28 (for Part 1) and up to approximately 2.5 years (for Part 2)

Outcome Measure Data

Analysis Population Description

All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.


Arm/Group Title	Part 1: Daratumumab Less Than (<) 4 mg/kg	Part 1: Daratumumab 4 mg/kg	Part 1:Daratumumab 8 mg/kg	Part 1: Daratumumab 16 mg/kg	Part 1:Daratumumab 24 mg/kg	Part 2: Daratumumab 8 mg/kg	Part 2: Daratumumab 16 mg/kg
Arm/Group Description:	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...
Arm/Group Description:	Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w), along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed	20	3	3	3	3	30	42
Measure Type: Number Unit of Measure: participants
	19	3	3	3	3	30	41

2.Secondary Outcome


Title	Overall Response Rate
Description	Overall response defined as percentage of participants who achieved st...
Description	Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >= 90% reduction in serum M-protein plus urine M-protein level < 100mg/24 hours; PR: >= 50 % reduction of serum M-protein and reduction in 24 hour urinary M-protein by >= 90% or to <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 FLC levels is required in place of the M-protein criteria.
Time Frame	Up to Week 28 (for Part 1) and Week 27 (for Part 2)

Outcome Measure Data

Analysis Population Description

All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. For Part 1, only participants treated with >= 4 mg/kg daratumumab were used for efficacy analyses and less than (<) 4 mg/kg doses were considered under the therapeutic levels.


Arm/Group Title	Part 1: Daratumumab 4 mg/kg	Part 1:Daratumumab 8 mg/kg	Part 1: Daratumumab 16 mg/kg	Part 1:Daratumumab 24 mg/kg	Part 2: Daratumumab 8 mg/kg	Part 2: Daratumumab 16 mg/kg
Arm/Group Description:	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...
Arm/Group Description:	Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w), along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed	3	3	3	3	30	42
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	33.3 (0.8 to 90.6)	0 (0 to 0)	33.3 (0.8 to 90.6)	66.7 (9.4 to 99.2)	10.0 (2.1 to 26.5)	35.7 (21.6 to 52.0)

3.Secondary Outcome


Title	Part 1: Time to Response
Description	Time to first response was defined as the time from the date of first ...
Description	Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Kaplan-Meier method was used to estimate the distribution of time to response and time to best response.
Time Frame	Up to Week 28

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Part 1: Daratumumab 4 mg/kg	Daratumumab 8 mg/kg	Daratumumab 16 mg/kg	Part 1:Daratumumab 24 mg/kg
Arm/Group Description:	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...
Arm/Group Description:	Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with participants received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with participants received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed	3	3	3	3
Median (95% Confidence Interval) Unit of Measure: months
Time to first response	NA ^[1] (1.2 to NA)	NA ^[2] (NA to NA)	8.4 ^[3] (NA to NA)	1.9 (0.5 to 1.9)
Time to best response	NA ^[4] (1.2 to NA)	NA ^[2] (NA to NA)	8.4 ^[3] (NA to NA)	1.9 (0.5 to 1.9)

[1]

Median and upper limit of confidence interval (CI) was not estimable due to insufficient number of participants with events.

[2]

Median and CI was not estimable due to insufficient number of participants with events.

[3]

Among the 3 participants on 16 mg/kg, only one participant had event, the median was set to this single uncensored value of "time to event" (defaults in PROC LIFETEST), no lower or upper bound of 95% CI calculated.

[4]

Median and upper limit of CI was not estimable due to insufficient number of participants with events.

4.Secondary Outcome


Title	Part 2: Time to Progression (TTP)
Description	TTP was defined as the number of days from the date of first infusion ...
Description	TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 g/dL); urine M-component and/or (the absolute increase must be >=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be >10 mg/dL); Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Median TTP was estimated by using the Kaplan-Meier method.
Time Frame	Up to Week 27

Outcome Measure Data

Analysis Population Description

All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.


Arm/Group Title	Daratumumab 8 mg/kg	Daratumumab 16 mg/kg
Arm/Group Description:	Participants were administered with...	Participants were administered with...
Arm/Group Description:	Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed	30	42
Median (95% Confidence Interval) Unit of Measure: months
	2.4 (1.4 to 3.5)	5.6 ^[1] (4.7 to NA)

[1]

Upper limit of CI was not estimable due to insufficient number of participants with events.

5.Secondary Outcome


Title	Part 2: Duration of Response as Assessed Using the Method of Kaplan-Meier
Description	Duration of response was calculated from the date of initial documenta...
Description	Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria.
Time Frame	Up to Week 27

Outcome Measure Data

Analysis Population Description

Subset of All-Treated Analysis Set included those who had overall response in Part 2.


Arm/Group Title	Daratumumab 8 mg/kg	Daratumumab 16 mg/kg
Arm/Group Description:	Participants were administered with...	Participants were administered with...
Arm/Group Description:	Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed	3	15
Median (Full Range) Unit of Measure: months
	6.9 (6.2 to 10.6)	NA ^[1] (5.6 to NA)

[1]

Median and upper limit of confidence interval (CI) was not estimable due to insufficient number of participants with events.

6.Secondary Outcome


Title	Part 2: Progression-Free Survival
Description	Progression free survival (PFS) was defined as the time between the da...
Description	Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first.
Time Frame	Up to Week 27

Outcome Measure Data

Analysis Population Description

All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.


Arm/Group Title	Daratumumab 8 mg/kg	Daratumumab 16 mg/kg
Arm/Group Description:	Participants were administered with...	Participants were administered with...
Arm/Group Description:	Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed	30	42
Median (95% Confidence Interval) Unit of Measure: months
	2.4 (1.4 to 3.5)	5.6 (4.2 to 8.1)

7.Secondary Outcome


Title	Part 2: Time to Response
Description	Time to first response was defined as the time from the date of first ...
Description	Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Time to VGPR (very good partial response) was defined as the time from the date of first dose of daratumumab to the date of initial documentation of VGPR response. The Kaplan-Meier method was used to estimate time to response.
Time Frame	Up to Week 27

Outcome Measure Data

Analysis Population Description

All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. Here 'n' (Number of Participants Analyzed) signifies number of participants analyzed at specific time point.


Arm/Group Title		Daratumumab 8 mg/kg	Daratumumab 16 mg/kg
Arm/Group Description:		Participants were administered with...	Participants were administered with...
Arm/Group Description:		Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed		30	42
Mean (Standard Deviation) Unit of Measure: months
Time to first response	Number Analyzed	3 participants	15 participants
Time to first response		1.36 (0.774)	1.33 (0.955)
Time to best response	Number Analyzed	3 participants	15 participants
Time to best response		1.36 (0.774)	2.46 (2.800)
Time to VGPR or better response	Number Analyzed	0 participants	4 participants
Time to VGPR or better response			0.49 (0.000)

8.Secondary Outcome


Title	Part 2: Overall Survival
Description	Overall Survival (OS) was defined as the number of days from administr...
Description	Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method.
Time Frame	Approximately 3 years

Outcome Measure Data

Analysis Population Description

All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug.


Arm/Group Title	Daratumumab 8 mg/kg	Daratumumab 16 mg/kg
Arm/Group Description:	Participants were administered with...	Participants were administered with...
Arm/Group Description:	Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
Overall Number of Participants Analyzed	30	42
Median (95% Confidence Interval) Unit of Measure: months
	18.2 (7.5 to 22.6)	34.3 ^[1] (19.9 to NA)

[1]

Upper limit of CI was not estimable due to insufficient number of participants with events.

Adverse Events

Time Frame	Up to Week 28 (for Part 1) and approximately 2.5 years
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Part 1 - <4 mg/kg	Part 1 - 4 mg/kg	Part 1 - 8 mg/kg	Part 1 - 16 mg/kg	Part 1 - 24 mg/kg	Part 2 - 8 mg/kg	Part 2 - 16 mg/kg
Arm/Group Description	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...	Participants were administered with...
Arm/Group Description	Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.	Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions.	Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period.
All-Cause Mortality
	Part 1 - <4 mg/kg	Part 1 - 4 mg/kg	Part 1 - 8 mg/kg	Part 1 - 16 mg/kg	Part 1 - 24 mg/kg	Part 2 - 8 mg/kg	Part 2 - 16 mg/kg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Part 1 - <4 mg/kg	Part 1 - 4 mg/kg	Part 1 - 8 mg/kg	Part 1 - 16 mg/kg	Part 1 - 24 mg/kg	Part 2 - 8 mg/kg	Part 2 - 16 mg/kg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	7/20 (35.00%)	0/3 (0.00%)	1/3 (33.33%)	2/3 (66.67%)	2/3 (66.67%)	12/30 (40.00%)	16/42 (38.10%)
Blood and lymphatic system disorders
Anaemia ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Neutropenia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Thrombocytopenia ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Cardiac disorders
Atrial Fibrillation ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Atrial Flutter ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Gastrointestinal disorders
Abdominal Pain ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Nausea ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
General disorders
Chest Pain ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Oedema Peripheral ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Pyrexia ^* 1	1/20 (5.00%)	0/3 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	0/3 (0.00%)	1/30 (3.33%)	2/42 (4.76%)
Hepatobiliary disorders
Hepatic Function Abnormal ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Immune system disorders
Cytokine Release Syndrome ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Infections and infestations
Bacteraemia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Bacterial Sepsis ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Herpes Zoster ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	2/42 (4.76%)
Influenza ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Metapneumovirus Infection ^* 1	0/20 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Pneumonia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	3/30 (10.00%)	3/42 (7.14%)
Respiratory Syncytial Virus Infection ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Urinary Tract Infection ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/30 (0.00%)	0/42 (0.00%)
Varicella ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Injury, poisoning and procedural complications
Limb Traumatic Amputation ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Spinal Compression Fracture ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Investigations
Blood Creatinine Increased ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Crossmatch Incompatible ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	3/42 (7.14%)
Free Haemoglobin Present ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
International Normalised Ratio Increased ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Metabolism and nutrition disorders
Hypokalaemia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Hypomagnesaemia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Musculoskeletal and connective tissue disorders
Back Pain ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Bone Pain ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Osteoporotic Fracture ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Nervous system disorders
Amnesia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Transient Ischaemic Attack ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Vith Nerve Paralysis ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Psychiatric disorders
Confusional State ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/30 (0.00%)	0/42 (0.00%)
* Indicates events were collected by non-systematic assessment 1 Term from vocabulary, MedDRA Version 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Part 1 - <4 mg/kg	Part 1 - 4 mg/kg	Part 1 - 8 mg/kg	Part 1 - 16 mg/kg	Part 1 - 24 mg/kg	Part 2 - 8 mg/kg	Part 2 - 16 mg/kg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	19/20 (95.00%)	3/3 (100.00%)	3/3 (100.00%)	3/3 (100.00%)	3/3 (100.00%)	30/30 (100.00%)	41/42 (97.62%)
Blood and lymphatic system disorders
Anaemia ^* 1	4/20 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	3/42 (7.14%)
Haemolysis ^* 1	3/20 (15.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Leukopenia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	4/42 (9.52%)
Lymphopenia ^* 1	2/20 (10.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Monocytopenia ^* 1	2/20 (10.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Neutropenia ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	4/42 (9.52%)
Thrombocytopenia ^* 1	3/20 (15.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/30 (6.67%)	3/42 (7.14%)
Cardiac disorders
Palpitations ^* 1	0/20 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Supraventricular Extrasystoles ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Tachycardia ^* 1	2/20 (10.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Eye disorders
Ocular Hyperaemia ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Vision Blurred ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/30 (6.67%)	5/42 (11.90%)
Gastrointestinal disorders
Abdominal Pain ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Aphthous Stomatitis ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/30 (6.67%)	0/42 (0.00%)
Constipation ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	4/30 (13.33%)	4/42 (9.52%)
Diarrhoea ^* 1	1/20 (5.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	9/30 (30.00%)	6/42 (14.29%)
Dry Mouth ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Dyspepsia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/30 (10.00%)	1/42 (2.38%)
Lip Oedema ^* 1	0/20 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Mouth Ulceration ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Nausea ^* 1	2/20 (10.00%)	1/3 (33.33%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	4/30 (13.33%)	10/42 (23.81%)
Oesophagitis ^* 1	0/20 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Stomatitis ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/30 (10.00%)	1/42 (2.38%)
Vomiting ^* 1	0/20 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	5/30 (16.67%)	2/42 (4.76%)
General disorders
Chest Discomfort ^* 1	0/20 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	1/42 (2.38%)
Chest Pain ^* 1	2/20 (10.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	5/42 (11.90%)
Chills ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/30 (10.00%)	5/42 (11.90%)
Fatigue ^* 1	2/20 (10.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	13/30 (43.33%)	19/42 (45.24%)
Influenza Like Illness ^* 1	3/20 (15.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/30 (3.33%)	1/42 (2.38%)
Oedema Peripheral ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/30 (10.00%)	1/42 (2.38%)
Pyrexia ^* 1	7/20 (35.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	12/30 (40.00%)	9/42 (21.43%)
Hepatobiliary disorders
Hepatic Function Abnormal ^* 1	0/20 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Immune system disorders
Cytokine Release Syndrome ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Hypersensitivity ^* 1	1/20 (5.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Infections and infestations
Gastroenteritis ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Herpes Zoster ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	4/30 (13.33%)	2/42 (4.76%)
Nasopharyngitis ^* 1	2/20 (10.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	7/30 (23.33%)	16/42 (38.10%)
Oral Candidiasis ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/30 (10.00%)	1/42 (2.38%)
Pneumonia ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	1/42 (2.38%)
Sinusitis ^* 1	0/20 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	4/42 (9.52%)
Upper Respiratory Tract Infection ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	8/30 (26.67%)	11/42 (26.19%)
Urinary Tract Infection ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/30 (6.67%)	2/42 (4.76%)
Viral Infection ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Vulvovaginal Candidiasis ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Investigations
Blood Creatine Phosphokinase Increased ^* 1	0/20 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	2/42 (4.76%)
Electrocardiogram QT Prolonged ^* 1	5/20 (25.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Free Haemoglobin Present ^* 1	4/20 (20.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Haptoglobin Decreased ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Lymphocyte Count Decreased ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Metabolism and nutrition disorders
Decreased Appetite ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	4/42 (9.52%)
Enzyme Abnormality ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Hypercalcaemia ^* 1	0/20 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	0/42 (0.00%)
Hyperglycaemia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	5/42 (11.90%)
Hyponatraemia ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	2/20 (10.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	4/30 (13.33%)	8/42 (19.05%)
Back Pain ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	3/30 (10.00%)	14/42 (33.33%)
Bone Pain ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	6/30 (20.00%)	4/42 (9.52%)
Kyphosis ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Musculoskeletal Chest Pain ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/30 (10.00%)	4/42 (9.52%)
Musculoskeletal Pain ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/30 (6.67%)	4/42 (9.52%)
Myalgia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	6/30 (20.00%)	1/42 (2.38%)
Pain in Extremity ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	6/42 (14.29%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	3/42 (7.14%)
Benign Neoplasm of Skin ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Nervous system disorders
Dizziness ^* 1	3/20 (15.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	5/30 (16.67%)	4/42 (9.52%)
Dysgeusia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/30 (6.67%)	0/42 (0.00%)
Headache ^* 1	1/20 (5.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/30 (10.00%)	4/42 (9.52%)
Hypoaesthesia ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	2/42 (4.76%)
Paraesthesia ^* 1	0/20 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Peripheral Sensory Neuropathy ^* 1	0/20 (0.00%)	1/3 (33.33%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	5/30 (16.67%)	1/42 (2.38%)
Psychiatric disorders
Confusional State ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Insomnia ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	4/30 (13.33%)	5/42 (11.90%)
Renal and urinary disorders
Pollakiuria ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Proteinuria ^* 1	9/20 (45.00%)	1/3 (33.33%)	3/3 (100.00%)	1/3 (33.33%)	1/3 (33.33%)	0/30 (0.00%)	0/42 (0.00%)
Renal Impairment ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Reproductive system and breast disorders
Prostatitis ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/30 (0.00%)	0/42 (0.00%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	1/30 (3.33%)	0/42 (0.00%)
Cough ^* 1	4/20 (20.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	6/30 (20.00%)	11/42 (26.19%)
Dysphonia ^* 1	0/20 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Dyspnoea ^* 1	0/20 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	8/30 (26.67%)	7/42 (16.67%)
Epistaxis ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/30 (6.67%)	0/42 (0.00%)
Laryngitis Allergic ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/30 (10.00%)	1/42 (2.38%)
Nasal Congestion ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	4/30 (13.33%)	7/42 (16.67%)
Oropharyngeal Pain ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/30 (6.67%)	5/42 (11.90%)
Productive Cough ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/30 (10.00%)	0/42 (0.00%)
Rhinitis Allergic ^* 1	1/20 (5.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	12/30 (40.00%)	10/42 (23.81%)
Throat Irritation ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	3/42 (7.14%)
Throat Tightness ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	3/42 (7.14%)
Skin and subcutaneous tissue disorders
Eczema Asteatotic ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
Erythema ^* 1	0/20 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	1/42 (2.38%)
Hyperhidrosis ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	3/30 (10.00%)	2/42 (4.76%)
Pruritus ^* 1	0/20 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	1/3 (33.33%)	0/3 (0.00%)	2/30 (6.67%)	1/42 (2.38%)
Rash ^* 1	1/20 (5.00%)	1/3 (33.33%)	1/3 (33.33%)	0/3 (0.00%)	0/3 (0.00%)	4/30 (13.33%)	2/42 (4.76%)
Vascular disorders
Flushing ^* 1	2/20 (10.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	1/30 (3.33%)	1/42 (2.38%)
Hot Flush ^* 1	0/20 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	2/30 (6.67%)	1/42 (2.38%)
Hypertension ^* 1	2/20 (10.00%)	0/3 (0.00%)	2/3 (66.67%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	3/42 (7.14%)
Hypotension ^* 1	2/20 (10.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/3 (0.00%)	0/30 (0.00%)	0/42 (0.00%)
* Indicates events were collected by non-systematic assessment 1 Term from vocabulary, MedDRA Version 18.0

Limitations and Caveats

[Not Specified]

More Information

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:	Senior Director
Organization:	Janssen Research & Development, LLC
EMail:	ClinicalTrialDisclosure@its.jnj.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Usmani SZ, Nahi H, Plesner T, Weiss BM, Bahlis NJ, Belch A, Voorhees PM, Laubach JP, van de Donk NWCJ, Ahmadi T, Uhlar CM, Wang J, Feng H, Qi M, Richardson PG, Lonial S. Daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma: final results from the phase 2 GEN501 and SIRIUS trials. Lancet Haematol. 2020 Jun;7(6):e447-e455. doi: 10.1016/S2352-3026(20)30081-8.

Adams HC 3rd, Stevenaert F, Krejcik J, Van der Borght K, Smets T, Bald J, Abraham Y, Ceulemans H, Chiu C, Vanhoof G, Usmani SZ, Plesner T, Lonial S, Nijhof I, Lokhorst HM, Mutis T, van de Donk NWCJ, Sasser AK, Casneuf T. High-Parameter Mass Cytometry Evaluation of Relapsed/Refractory Multiple Myeloma Patients Treated with Daratumumab Demonstrates Immune Modulation as a Novel Mechanism of Action. Cytometry A. 2019 Mar;95(3):279-289. doi: 10.1002/cyto.a.23693. Epub 2018 Dec 11.

Krejcik J, Frerichs KA, Nijhof IS, van Kessel B, van Velzen JF, Bloem AC, Broekmans MEC, Zweegman S, van Meerloo J, Musters RJP, Poddighe PJ, Groen RWJ, Chiu C, Plesner T, Lokhorst HM, Sasser AK, Mutis T, van de Donk NWCJ. Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab. Clin Cancer Res. 2017 Dec 15;23(24):7498-7511. doi: 10.1158/1078-0432.CCR-17-2027. Epub 2017 Oct 12.

Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, Groen RW, van Duin M, Sonneveld P, Minnema MC, Zweegman S, Chiu C, Bloem AC, Mutis T, Lokhorst HM, Sasser AK, van de Donk NW. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood. 2016 Aug 18;128(7):959-70. doi: 10.1182/blood-2016-03-703439. Epub 2016 Jun 15.

Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, Minnema MC, Lassen U, Krejcik J, Palumbo A, van de Donk NW, Ahmadi T, Khan I, Uhlar CM, Wang J, Sasser AK, Losic N, Lisby S, Basse L, Brun N, Richardson PG. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med. 2015 Sep 24;373(13):1207-19. doi: 10.1056/NEJMoa1506348. Epub 2015 Aug 26.

Layout table for additonal information

Responsible Party:	Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:	NCT00574288
Other Study ID Numbers:	CR101876 GEN501 ( Other Identifier: Janssen Research & Development, LLC ) DARA-GEN501 ( Other Identifier: Janssen Research & Development, LLC ) 2007-003783-22 ( EudraCT Number )
First Submitted:	December 14, 2007
First Posted:	December 17, 2007
Results First Submitted:	October 21, 2016
Results First Posted:	March 9, 2017
Last Update Posted:	April 27, 2018

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