Back to resultsA Study of JNJ-54767414 (Daratumumab) in Combination With Bortezomib and Dexamethasone (D-Vd) in Japanese Participants With Relapsed or Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
JNJ-54767414 (Daratumumab)
Bortezomib
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Daratumumab, JNJ-54767414, Bortezomib, Dexamethasone
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
JNJ-54767414 (Daratumumab) +Bortezomib+Dexamethasone
Arm Description
Participants will be administered JNJ-54767414 (daratumumab) intravenously at a dose of 16 milligram per kilogram (mg/kg) weekly for the first 3 cycles, then on Day 1 of Cycles 4-8 (every 3 weeks), and then on Day 1 of subsequent cycles (every 4 weeks), First 8 Cycles are 21-day cycles; Cycles 9 and onwards are 28-day cycles. Bortezomib at a dose of 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8 and 11 of each 21-day cycle for 8 treatment cycles and Dexamethasone orally at 20 mg on Day 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 bortezomib treatment cycles.
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Secondary Outcome Measures
Minimum Observed Serum Concentration (Cmin) of JNJ-54767414 (Daratumumab)
The Cmin is the maximum observed serum concentration of JNJ-54767414.
Maximum Observed Serum Concentration (Cmax) of JNJ-54767414 (Daratumumab)
The Cmax is the maximum observed serum concentration of JNJ-54767414.
Serum Concentration of JNJ-54767414 (Daratumumab) Antibodies
Serum levels of antibodies to Daratumumab for evaluation of potential immunogenicity.
Percentage of Participants With Overall Response Rate (ORR)
Overall response rate is defined as the percentage of participants who achieve complete response or partial response according to the International Myeloma Working Group criteria, during or after study treatment.
Percentage of Participants with Complete Response (CR) or better
CR is Defined as the proportion of Participants achieving CR (including sCR) according to the IMWG criteria.
Percentage of Participants with a Very Good Partial Response (VGPR) or better
VGPR is defined as a greater than 90% reduction in serum myeloma protein (M-protein) plus urine myeloma protein less than 100 milligram (mg) per 24 hours.
Time to Response
Time to response is defined as the time from the date of first dose of study treatment to the date of the first documentation of observed response (CR or PR).
Full Information
NCT ID
NCT02497378
First Posted
July 10, 2015
Last Updated
March 5, 2019
Sponsor
Janssen Pharmaceutical K.K.
1. Study Identification
Unique Protocol Identification Number
NCT02497378
Brief Title
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
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
July 10, 2015 (Actual)
Primary Completion Date
March 6, 2018 (Actual)
Study Completion Date
March 6, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Pharmaceutical K.K.
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Daratumumab, JNJ-54767414, Bortezomib, Dexamethasone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
JNJ-54767414 (Daratumumab) +Bortezomib+Dexamethasone
Arm Type
Experimental
Arm Description
Participants will be administered JNJ-54767414 (daratumumab) intravenously at a dose of 16 milligram per kilogram (mg/kg) weekly for the first 3 cycles, then on Day 1 of Cycles 4-8 (every 3 weeks), and then on Day 1 of subsequent cycles (every 4 weeks), First 8 Cycles are 21-day cycles; Cycles 9 and onwards are 28-day cycles. Bortezomib at a dose of 1.3 milligram per meter square (mg/m^2) subcutaneously (SC) on Days 1, 4, 8 and 11 of each 21-day cycle for 8 treatment cycles and Dexamethasone orally at 20 mg on Day 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 bortezomib treatment cycles.
Intervention Type
Drug
Intervention Name(s)
JNJ-54767414 (Daratumumab)
Intervention Description
JNJ-54767414 (Daratumumab) will be administered as an Intravenous (IV) infusion at a dose of 16 milligram per kilogram (mg/kg) weekly for the first 3 cycles, on Day 1 of Cycles 4-8 (every 3 weeks), and then on Day 1 of subsequent cycles (every 4 weeks). First 8 Cycles are 21-day cycles; Cycles 9 and onwards are 28-day cycles.
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
VELCADE
Intervention Description
Bortezomib will be administered at a dose of 1.3 mg/m^2 subcutaneously (SC) on Day 1, 4, 8 and 11 of each 21-day cycle. Eight Bortezomib treatment cycles are to be administered.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone will be administered orally at 20 mg on Day 1, 2, 4, 5, 8, 9, 11 and 12 of the first 8 bortezomib treatment cycles (except for Cycles 1-3). In Cycles 1-3, participants receive dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11, 12 and 15. During weeks when the participants receives an infusion of daratumumab, dexamethasone will be administered at a dose of 20 mg IV or orally (PO) (only if IV is not available) before the daratumumab infusion as preinfusion medication.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE was any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame
Approximately 2 years
Secondary Outcome Measure Information:
Title
Minimum Observed Serum Concentration (Cmin) of JNJ-54767414 (Daratumumab)
Description
The Cmin is the maximum observed serum concentration of JNJ-54767414.
Time Frame
Approximately 2 years
Title
Maximum Observed Serum Concentration (Cmax) of JNJ-54767414 (Daratumumab)
Description
The Cmax is the maximum observed serum concentration of JNJ-54767414.
Time Frame
Approximately 2 years
Title
Serum Concentration of JNJ-54767414 (Daratumumab) Antibodies
Description
Serum levels of antibodies to Daratumumab for evaluation of potential immunogenicity.
Time Frame
Approximately 2 years
Title
Percentage of Participants With Overall Response Rate (ORR)
Description
Overall response rate is defined as the percentage of participants who achieve complete response or partial response according to the International Myeloma Working Group criteria, during or after study treatment.
Time Frame
Approximately 2 years
Title
Percentage of Participants with Complete Response (CR) or better
Description
CR is Defined as the proportion of Participants achieving CR (including sCR) according to the IMWG criteria.
Time Frame
Approximately 2 years
Title
Percentage of Participants with a Very Good Partial Response (VGPR) or better
Description
VGPR is defined as a greater than 90% reduction in serum myeloma protein (M-protein) plus urine myeloma protein less than 100 milligram (mg) per 24 hours.
Time Frame
Approximately 2 years
Title
Time to Response
Description
Time to response is defined as the time from the date of first dose of study treatment to the date of the first documentation of observed response (CR or PR).
Time Frame
Approximately 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Pharmaceutical K.K. Clinical Trial
Organizational Affiliation
Janssen Pharmaceutical K.K.
Official's Role
Study Director
Facility Information:
City
Hiroshima
Country
Japan
City
Hitachi
Country
Japan
City
Nagoya
Country
Japan
City
Shibuya
Country
Japan
City
Tachikawa
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
29260507
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.
Results Reference
derived
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR107666&attachmentIdentifier=4f56a255-b7e2-4ed1-b927-a68e44a5d4fd&fileName=CR107666_CSR.pdf&versionIdentifier=
Description
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)
Learn more about this trial
A Study of JNJ-54767414 (Daratumumab) in Combination With Bortezomib and Dexamethasone (D-Vd) in Japanese Participants With Relapsed or Refractory Multiple Myeloma
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