Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 54767414MMY1003 | Other Identifier | Janssen Research & Development, LLC |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Dose Escalation Part | Experimental | Participants will receive single dose of daratumumab from Week 1 till Week 3 (Period 1 - single dosing period) followed by 6 weekly doses of daratumumab until Week 9 (Period 2 - weekly dosing period) and every 2 weeks for 8 infusions and then once every 4 weeks from Week 26 until disease progression, intolerability, or other reasons for treatment discontinuation (Period 3 - less intense dosing period). A dose of 8 milligram per kilogram (mg/kg) will be chosen as the starting dose and will be escalated to 16 mg/kg if the 8 mg/kg is determined safe and tolerated by study evaluation team (SET). |
|
| Part 2: Pharmacokinetic (PK) Expansion Part | Experimental | Participants will receive daratumumab at 16 mg/kg in 3 periods as given in the Part 1. |
|
| Part 3: Safety Expansion Part | Experimental | Participants will receive daratumumab 16 mg/kg every week for 8 weeks followed by every 2 weeks for an additional 16 weeks, and then every 4 weeks thereafter. Participants will be treated with daratumumab until disease progression, intolerability, or any other reasons for treatment discontinuation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Daratumumab | Drug | Intravenous (IV) infusion of 8 mg/kg or 16 mg/kg daratumumab. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability (Part 1,2 and 3) | 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. | 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. | 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. | 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]). | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
Inclusion Criteria:
Part 1 and 2:
Part 3:
Exclusion Criteria:
Part 1 and 2:
Part 3:
- Received anti-myeloma treatment within 2 weeks before Cycle 1, Day 1
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing | China | |||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37022569 | Derived | Li X, Dosne AG, Perez Ruixo C, Perez Ruixo JJ. Pharmacodynamic-Mediated Drug Disposition (PDMDD) Model of Daratumumab Monotherapy in Patients with Multiple Myeloma. Clin Pharmacokinet. 2023 May;62(5):761-777. doi: 10.1007/s40262-023-01232-8. Epub 2023 Apr 6. | |
| 36301338 | Derived | 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. |
| Label | URL |
|---|---|
| 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 | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 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. | Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward) |
| 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). | 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. | From the date of initial documentation of a response to the date of first documented evidence of progressive disease (approximately 2 years) |
| 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. | 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. | 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 | Up to Follow-up Phase-Week 8 |
| Hangzhou |
| China |
| Shanghai | China |
| Suzhou | China |
| Tianjin | China |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C556306 | daratumumab |
Not provided
Not provided
Not provided