The purpose of this study is to evaluate the tolerability, safety and the pharmacokinetic (PK) profile of daratumumab in Chinese participants with relapsed or refractory multiple myeloma (RRMM) who failed at least 2 prior lines of systemic therapy (Part 1 and Part 2); and to evaluate the tolerability and safety of daratumumab in Chinese participants whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) and who have demonstrated disease progression on the last therapy (Part 3).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Intravenous (IV) infusion of 8 mg/kg or 16 mg/kg daratumumab.
Unnamed facility
Beijing, China
Unnamed facility
Hangzhou, China
Unnamed facility
Shanghai, China
Unnamed facility
Suzhou, China
Unnamed facility
Tianjin, China
Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability (Part 1,2 and 3)
Time frame: From the time of signing of informed consent form (ICF) until 30 days after the last study drug dose (approximately 2 years)
Maximum Observed Plasma Concentration (Cmax) (Part 1 and 2)
The Cmax is the maximum observed plasma concentration.
Time frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Trough Analyte Concentration (Ctrough) (Part 1 and 2)
The (Ctrough) is the concentration before dosing just prior to the beginning of a doing interval.
Time frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Area Under the Plasma Concentration-Time Curve (AUC) (Part 1 and 2)
AUC is defined as area under the plasma concentration-time curve.
Time frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Systemic Clearance (CL) (Part 1 and 2)
Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC \[0-infinity\]).
Time frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Elimination Half-Life (t1/2) (Part 1 and 2)
Elimination half-life (t\[1/2\]) is associated with the terminal slope (lambda \[z\]) of the semi-logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).
Time frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Volume of Distribution (Vd) (Part 1 and 2)
The Vd is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Overall Response Rate (ORR)
ORR is defined as the proportion of participants who achieve complete response \[CR\] (including sCR) according to the IMWG criteria, during or after the study treatment. IMWG criteria CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and less than (\<)5 % plasma cells (PCs) in bone marrow; sCR: CR along with normal free light chain (FLC) ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry. Partial Response (PR): more than equal to (\>=) 50percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 mg/24 hours; VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or \>= 90 % reduction in serum M-protein plus urine M-protein less than (\<)100 mg/24 hours.
Time frame: From the date of first dose of daratumumab to the date of initial documentation of progressive disease (approximately 2 years)
Time to Response
Time to response is defined as the time between the date of first dosing and the first efficacy evaluation that the participant has met all criteria for PR (including VGPR) or CR (including sCR).
Time frame: From the date of first dose of daratumumab to the date of initial documentation of a response (approximately 2 years)
Duration of Response
Duration of Response will be calculated from date of initial documentation of a response (CR/PR) to date of first documented evidence of PD. IMWG criteria for PD- Increase of 25% from lowest response value in any one of 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), only in participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase must be \>10 mg/dL), only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC percentage (absolute percentage must be \>=10%). Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed to PC proliferative disorder.
Time frame: From the date of initial documentation of a response to the date of first documented evidence of progressive disease (approximately 2 years)
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Progression-Free Survival (PFS)
PFS is defined as the time from the date of first dose of daratumumab to the date of first documented Progressive disease (PD), as per International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first.
Time frame: From the date of first dose of daratumumab to the date of first documented progressive disease (approximately 2 years)
Overall Survival (OS)
Overall survival (OS) is measured from the date of first dose of daratumumab to the date of the participant's death.
Time frame: From the date of first dose of daratumumab to the date of the participant's death (approximately 2 years)
Number of Participants With Incidence of Antibodies to Daratumumab
Time frame: Up to Follow-up Phase-Week 8