Clinical trial NCT02852837: Dose Escalation Study of JNJ-54767414 (Daratumumab) in Chinese Participants With Relapsed or Refractory Multiple Myeloma Who Failed at Least 2 Prior Lines of Systemic Therapy
Official title: A Phase 1, Open-label, Dose Escalation Study of JNJ-54767414 (Daratumumab) in Chinese Subjects With Relapsed or Refractory Multiple Myeloma Who Failed at Least 2 Prior Lines of Systemic Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2016-08-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

Part 1 and 2:

* Chinese participant who must be at least 20 years of age
* Documented multiple myeloma (MM) with measurable disease according to protocol-defined criteria
* Relapsed or refractory multiple myeloma after receiving at least 2 prior lines of therapy
* Eastern Cooperative Oncology Group performance status score of 0, 1, or 2
* Adequate recovery from prior therapy

Part 3:

* Chinese participants who must be at least 18 years of age
* Received both 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)
* Documented evidence of progressive disease (PD) based on investigator's determination of response as defined by the International Myeloma Working Group (IMWG) criteria on or after their last regimen

Exclusion Criteria:

Part 1 and 2:

* Received daratumumab or other anti-CD38 therapies previously
* Previously received an allogenic stem cell transplant or has received an autologous stem cell transplantation within 12 weeks
* Exhibiting clinical signs of meningeal involvement of multiple myeloma
* Known chronic obstructive pulmonary disease, known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification
* Known clinically significant cardiac disease
* Known to be seropositive for human immunodeficiency virus, hepatitis B or known to have a history of hepatitis C
* Has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
* Abnormal laboratory values according to protocol-defined parameters at screening

Part 3:

- Received anti-myeloma treatment within 2 weeks before Cycle 1, Day 1

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability (Part 1,2 and 3)
timeFrame: From the time of signing of informed consent form (ICF) until 30 days after the last study drug dose (approximately 2 years)
measure: Maximum Observed Plasma Concentration (Cmax) (Part 1 and 2)
timeFrame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
measure: Trough Analyte Concentration (Ctrough) (Part 1 and 2)
timeFrame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
measure: Area Under the Plasma Concentration-Time Curve (AUC) (Part 1 and 2)
timeFrame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
measure: Systemic Clearance (CL) (Part 1 and 2)
timeFrame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
measure: Elimination Half-Life (t1/2) (Part 1 and 2)
timeFrame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
measure: Volume of Distribution (Vd) (Part 1 and 2)
timeFrame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: From the date of first dose of daratumumab to the date of initial documentation of progressive disease (approximately 2 years)
measure: Time to Response
timeFrame: From the date of first dose of daratumumab to the date of initial documentation of a response (approximately 2 years)
measure: Duration of Response
timeFrame: From the date of initial documentation of a response to the date of first documented evidence of progressive disease (approximately 2 years)
measure: Progression-Free Survival (PFS)
timeFrame: From the date of first dose of daratumumab to the date of first documented progressive disease (approximately 2 years)
measure: Overall Survival (OS)
timeFrame: From the date of first dose of daratumumab to the date of the participant's death (approximately 2 years)
measure: Number of Participants With Incidence of Antibodies to Daratumumab
timeFrame: Up to Follow-up Phase-Week 8
Other outcomes:
Locations:
city: Beijing
country: China
city: Hangzhou
country: China
city: Shanghai
country: China
city: Suzhou
country: China
city: Tianjin
country: China
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Jing H, Yang L, Qi J, Qiu L, Fu C, Li J, Yang M, Qi M, Fan N, Ji J, Lu J, Li Y, Jin J. Safety and efficacy of daratumumab in Chinese patients with relapsed or refractory multiple myeloma: a phase 1, dose-escalation study (MMY1003). Ann Hematol. 2022 Dec;101(12):2679-2690. doi: 10.1007/s00277-022-04951-3. Epub 2022 Oct 27.