A Study of Daratumumab in Japanese Participants With Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the tolerability and safety of Daratumumab in Japanese participants with relapsed (the return of a medical problem) or refractory (not responding to treatment) multiple myeloma (cancer of plasma cells in bone marrow, characterized by the presence of abnormal proteins in the blood).

Detailed Description
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This is a Phase 1, 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, a Treatment Phase, and a Follow-up Phase. The Treatment Phase consists of 2 parts: intense dosing regimen and less intense dosing regimen. Follow-up phase will be until 8 weeks after last dose administration/death/lost to follow up/consent withdrawal for study participation or study end, whichever occurs first. The primary endpoints will be Dose Limiting Toxicity (DLTs) and overall Adverse Events (AEs) profiling. Participants' safety will be monitored throughout the study.

Official Title
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A Phase I Study of JNJ-54761414 (Daratumumab) in Japanese Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Daratumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants proven to have symptomatic (having symptoms) multiple myeloma according the International Myeloma Working Group (IMWG) diagnostic criteria Participant must have measurable disease defined by either or both the following measurements: a) Serum M-protein greater than or equal to (>=) 1 gram per deciliter (g/dL) (>=10 gram per liter [g/L]) (except for serum immunoglobulin A [IgA] M-protein >= 0.5 g/dL); b) Urine M-protein >=200 milligram per 24 hour (mg/24 h); in case immunoglobulin D [IgD] or immunoglobulin E [IgE] M-protein, quantification should be performed Participant must have relapsed or refractory multiple myeloma after receiving at least 2 previous therapies, and without further established treatment options Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 Participant must have life expectancy greater than (>) 3 months Exclusion Criteria: Participant has received daratumumab or other anti-cluster of differentiation 38 (anti-CD38) therapies previously Participant has received anti-myeloma treatment within 2 weeks before administration of the study drug Participant has previously received an allogenic stem cell transplant; or participant has received autologous stem cell transplantation (ASCT) within 12 weeks before administration of the study drug Participant has a history of malignancy (other than multiple myeloma) within 5 years before administration of the study drug Participant is exhibiting clinical signs of meningeal involvement of multiple myeloma

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daratumumab 8 milligram per kilogram (mg/kg)<br>Participants will be administered intravenously with daratumumab at a dose of 8 mg/kg up to 8 weeks (total 7 infusions). After 8 weeks, participants will receive daratumumab intravenously two times in every 2 weeks until Week 24 followed by one time in 4 weeks until study discontinuation. | Drug: Daratumumab<br>* Participants will be administered intravenously with daratumumab at a dose of 8 or 16 mg/kg up to 8 weeks (total 7 infusions). After 8 weeks, participants will receive daratumumab intravenously at a same dose, two times in every 2 weeks until Week 24 followed by one time in 4 weeks until study discontinuation. If the dose exceeds 24 mg/kg, then it will be considered as overdose in this study.<br>* Other names: JNJ-54767414;|
| Experimental: Daratumumab 16 mg/kg<br>Participants will be administered intravenously with daratumumab at a dose of 16 mg/kg up to 8 weeks (total 7 infusions). After 8 weeks, participants will receive daratumumab intravenously at a same dose, two times in every 2 weeks until Week 24 followed by one time in 4 weeks until study discontinuation. | Drug: Daratumumab<br>* Participants will be administered intravenously with daratumumab at a dose of 8 or 16 mg/kg up to 8 weeks (total 7 infusions). After 8 weeks, participants will receive daratumumab intravenously at a same dose, two times in every 2 weeks until Week 24 followed by one time in 4 weeks until study discontinuation. If the dose exceeds 24 mg/kg, then it will be considered as overdose in this study.<br>* Other names: JNJ-54767414;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities (DLT) | The Dose-Limiting Toxicities (DLTs) are based on drug-related adverse events and defined as any of the following events: Infusion-related reactions, non-hematologic toxicity of Grade 3 or higher, or hematologic toxicity. | Day 1 up to Day 36 | 
| Number of Participants affected by Adverse Events | An AE is any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was 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. | Baseline up to 4 Weeks after the last dose of study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Overall Response | The Overall Response rate is defined according to Internal Myeloma Working Group criteria based on participants achieving greater than or equal to (>=) partial Response, including participants achieving stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR). Percentage of participants with overall response will be reported. | Baseline until disease progression, unmanageable adverse event or death, whichever occurs first, up to 1 year | 
| 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. | Baseline until first documented response or up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Daratumumab, JNJ-54767414, Phase 1, Relapse, Refractory