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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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Daratumumab
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Part 1: Dose Escalation Part

Part 2: Pharmacokinetic (PK) Expansion Part

Part 3: Safety Expansion Part

Arm Description

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).

Participants will receive daratumumab at 16 mg/kg in 3 periods as given in the Part 1.

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.

Outcomes

Primary Outcome Measures

Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability (Part 1,2 and 3)
Maximum Observed Plasma Concentration (Cmax) (Part 1 and 2)
The Cmax is the maximum observed plasma concentration.
Trough Analyte Concentration (Ctrough) (Part 1 and 2)
The (Ctrough) is the concentration before dosing just prior to the beginning of a doing interval.
Area Under the Plasma Concentration-Time Curve (AUC) (Part 1 and 2)
AUC is defined as area under the plasma concentration-time curve.
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]).
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).
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.

Secondary Outcome Measures

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.
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).
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.
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.
Overall Survival (OS)
Overall survival (OS) is measured from the date of first dose of daratumumab to the date of the participant's death.
Number of Participants With Incidence of Antibodies to Daratumumab

Full Information

First Posted
July 29, 2016
Last Updated
November 12, 2020
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02852837
Brief Title
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

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
September 26, 2016 (Actual)
Primary Completion Date
December 13, 2019 (Actual)
Study Completion Date
December 13, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
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, 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Dose Escalation Part
Arm Type
Experimental
Arm Description
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).
Arm Title
Part 2: Pharmacokinetic (PK) Expansion Part
Arm Type
Experimental
Arm Description
Participants will receive daratumumab at 16 mg/kg in 3 periods as given in the Part 1.
Arm Title
Part 3: Safety Expansion Part
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Other Intervention Name(s)
JNJ-54767414
Intervention Description
Intravenous (IV) infusion of 8 mg/kg or 16 mg/kg daratumumab.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability (Part 1,2 and 3)
Time Frame
From the time of signing of informed consent form (ICF) until 30 days after the last study drug dose (approximately 2 years)
Title
Maximum Observed Plasma Concentration (Cmax) (Part 1 and 2)
Description
The Cmax is the maximum observed plasma concentration.
Time Frame
Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Title
Trough Analyte Concentration (Ctrough) (Part 1 and 2)
Description
The (Ctrough) is the concentration before dosing just prior to the beginning of a doing interval.
Time Frame
Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Title
Area Under the Plasma Concentration-Time Curve (AUC) (Part 1 and 2)
Description
AUC is defined as area under the plasma concentration-time curve.
Time Frame
Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Title
Systemic Clearance (CL) (Part 1 and 2)
Description
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]).
Time Frame
Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Title
Elimination Half-Life (t1/2) (Part 1 and 2)
Description
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).
Time Frame
Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Title
Volume of Distribution (Vd) (Part 1 and 2)
Description
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.
Time Frame
Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
From the date of first dose of daratumumab to the date of initial documentation of progressive disease (approximately 2 years)
Title
Time to Response
Description
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).
Time Frame
From the date of first dose of daratumumab to the date of initial documentation of a response (approximately 2 years)
Title
Duration of Response
Description
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.
Time Frame
From the date of initial documentation of a response to the date of first documented evidence of progressive disease (approximately 2 years)
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
From the date of first dose of daratumumab to the date of first documented progressive disease (approximately 2 years)
Title
Overall Survival (OS)
Description
Overall survival (OS) is measured from the date of first dose of daratumumab to the date of the participant's death.
Time Frame
From the date of first dose of daratumumab to the date of the participant's death (approximately 2 years)
Title
Number of Participants With Incidence of Antibodies to Daratumumab
Time Frame
Up to Follow-up Phase-Week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Beijing
Country
China
City
Hangzhou
Country
China
City
Shanghai
Country
China
City
Suzhou
Country
China
City
Tianjin
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
36301338
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.
Results Reference
derived
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&amp;parentIdentifier=CR108180&amp;attachmentIdentifier=73dbcc08-6b56-4322-a2db-6ec64f3e2398&amp;fileName=CR108180_CSR_Synopsis.pdf&amp;versionIdentifier=
Description
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

Learn more about this trial

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

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