Clinical trial NCT02497378: A Study of JNJ-54767414 (Daratumumab) in Combination With Bortezomib and Dexamethasone (D-Vd) in Japanese Participants With Relapsed or Refractory Multiple Myeloma
Official title: A Phase 1b Study of JNJ-54767414 (Daratumumab) in Combination With Bortezomib and Dexamethasone (D-Vd) in Japanese Patients With Relapsed or Refractory Multiple Myeloma (MM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Daratumumab
JNJ-54767414
Bortezomib
Dexamethasone
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2015-07-14
Enrollment: 8
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the tolerability and safety of JNJ-54767414 (daratumumab) in Combination With Bortezomib and Dexamethasone (D-Vd) in Japanese participants with relapsed (the return of a medical problem) or refractory (not responding to treatment) multiple myeloma.

Detailed description: This is an open-label (all participants and study personnel will know the identity of the study treatments) and multicenter (study conducted at multiple sites) study in Japanese participants. The study will include a Screening Phase (21 days prior to Cycle 1 Day 1); open-label treatment phase (from Cycle 1 Day 1 until study treatment discontinuation, disease progression, unacceptable toxicity, or other reasons), and a Follow-up Phase. Bortezomib and Dexamethasone will be administered along with JNJ-54767414 for first 8 treatment cycles. Follow-up Phase begins immediately following the End-of-Treatment Visit, and will continue until 8 weeks after last study treatment, death, loss to follow-up, consent withdrawal for study participation, or study end, whichever occurs first. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Participants proven to have symptomatic (having symptoms) multiple myeloma (MM) according the International Myeloma Working Group (IMWG) diagnostic criteria
* Participant must have documented MM as defined by following criteria: Monoclonal plasma cells in the bone marrow 10 percent (%), or presence of a biopsy-proven plasmacytoma at some point in their disease history, disease measurements: a) Serum M-protein greater than or equal to (\>=) 1 gram per deciliter (g/dL) (\>=10 gram per liter \[g/L\]) b) Serum immunoglobulin A \[IgA\] M-protein \>= 0.5 g/dL); c) Urine M-protein \>=200 milligram per 24 hour (mg/24 h); d) Serum immunoglobulin free light chain \>=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
* Participant must have received at least 1 prior line of therapy for MM
* Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
* Participant must have achieved a response (partial response \[PR\] or better based on investigator's determination of response by the IMWG criteria) to at least 1 prior regimen

Exclusion Criteria:

* Participant has received daratumumab or other anti-cluster of differentiation 38 (anti-CD38) therapies previously
* Is refractory to bortezomib or another PI, like ixazomib and carfilzomib (had progression of disease while receiving bortezomib therapy or within 60 days of ending bortezomib therapy or another PI therapy, like ixazomib and carfilzomib
* Is intolerant to bortezomib (ie, discontinued due to any adverse event while on bortezomib treatment)
* Has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of daratumumab first administration. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day \[mg/day\] for a maximum of 4 days) before treatment. A list of anti-myeloma treatments with the corresponding pharmacokinetic half-lives is provided in the Site Investigational Product Procedures Manual (IPPM)
* Has a history of malignancy (other than multiple myeloma) within 3 years before the date of daratumumab first administration
* Has any concurrent medical condition or disease (eg, active systemic infection, pulmonary impairment) that is likely to interfere with study procedures

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Minimum Observed Serum Concentration (Cmin) of JNJ-54767414 (Daratumumab)
timeFrame: Approximately 2 years
measure: Maximum Observed Serum Concentration (Cmax) of JNJ-54767414 (Daratumumab)
timeFrame: Approximately 2 years
measure: Serum Concentration of JNJ-54767414 (Daratumumab) Antibodies
timeFrame: Approximately 2 years
measure: Percentage of Participants With Overall Response Rate (ORR)
timeFrame: Approximately 2 years
measure: Percentage of Participants with Complete Response (CR) or better
timeFrame: Approximately 2 years
measure: Percentage of Participants with a Very Good Partial Response (VGPR) or better
timeFrame: Approximately 2 years
measure: Time to Response
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Hiroshima
country: Japan
city: Hitachi
country: Japan
city: Nagoya
country: Japan
city: Shibuya
country: Japan
city: Tachikawa
country: Japan
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Iida S, Ichinohe T, Shinagawa A, Suzuki K, Takezako N, Aoki M. Safety and efficacy of daratumumab in combination with bortezomib and dexamethasone in Japanese patients with relapsed or refractory multiple myeloma. Int J Hematol. 2018 Apr;107(4):460-467. doi: 10.1007/s12185-017-2390-2. Epub 2017 Dec 19.