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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

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ClinicalTrials.gov Identifier: NCT02852837
Recruitment Status : Active, not recruiting
First Posted : August 2, 2016
Last Update Posted : December 6, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE July 29, 2016
First Posted Date  ICMJE August 2, 2016
Last Update Posted Date December 6, 2019
Actual Study Start Date  ICMJE September 26, 2016
Estimated Primary Completion Date January 13, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2019)
  • 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) ]
  • Maximum Observed Plasma Concentration (Cmax) (Part 1 and 2) [ Time Frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward) ]
    The Cmax is the maximum observed plasma concentration.
  • Trough Analyte Concentration (Ctrough) (Part 1 and 2) [ Time Frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward) ]
    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) [ Time Frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward) ]
    AUC is defined as area under the plasma concentration-time curve.
  • Systemic Clearance (CL) (Part 1 and 2) [ Time Frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward) ]
    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) [ Time Frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward) ]
    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) [ Time Frame: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 29, 2016)
  • Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: Up to Follow-up Phase-Week 8 ]
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to Follow-up Phase-Week 8 ]
    The Cmax is the maximum observed plasma concentration.
  • Trough Analyte Concentration (Ctrough) [ Time Frame: Up to Follow-up Phase-Week 8 ]
    The (Ctrough) is the concentration before dosing just prior to the beginning of a doing interval.
  • Area Under the Plasma Concentration-Time Curve (AUC) [ Time Frame: Up to Follow-up Phase-Week 8 ]
    AUC is defined as area under the plasma concentration-time curve.
  • Systemic Clearance (CL) [ Time Frame: Up to Follow-up Phase-Week 8 ]
    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) [ Time Frame: Up to Follow-up Phase-Week 8 ]
    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) [ Time Frame: Up to Follow-up Phase-Week 8 ]
    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.
Change History Complete list of historical versions of study NCT02852837 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 26, 2017)
  • Overall Response Rate (ORR) [ Time Frame: From the date of first dose of daratumumab to the date of initial documentation of progressive disease (approximately 2 years) ]
    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 Frame: From the date of first dose of daratumumab to the date of initial documentation of a response (approximately 2 years) ]
    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 [ Time Frame: From the date of initial documentation of a response to the date of first documented evidence of progressive disease (approximately 2 years) ]
    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) [ Time Frame: From the date of first dose of daratumumab to the date of first documented progressive disease (approximately 2 years) ]
    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) [ Time Frame: From the date of first dose of daratumumab to the date of the participant's death (approximately 2 years) ]
    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 [ Time Frame: Up to Follow-up Phase-Week 8 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 29, 2016)
  • Overall Response Rate (ORR) [ Time Frame: Up to Follow-up Phase-Week 8 ]
    ORR is defined as the proportion of participants who achieve 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. 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 Frame: Up to Follow-up Phase-Week 8 ]
    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) and CR (including sCR).
  • Number of Participants With Incidence of Antibodies to Daratumumab [ Time Frame: Up to Follow-up Phase-Week 8 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE Drug: Daratumumab
Intravenous (IV) infusion of 8 mg/kg or 16 mg/kg daratumumab.
Other Name: JNJ-54767414
Study Arms  ICMJE
  • Experimental: Part 1: Dose Escalation Part
    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).
    Intervention: Drug: Daratumumab
  • Experimental: Part 2: Pharmacokinetic (PK) Expansion Part
    Participants will receive daratumumab at 16 mg/kg in 3 periods as given in the Part 1.
    Intervention: Drug: Daratumumab
  • Experimental: Part 3: Safety Expansion Part
    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: Drug: Daratumumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 9, 2017)
50
Original Estimated Enrollment  ICMJE
 (submitted: July 29, 2016)
20
Estimated Study Completion Date  ICMJE January 31, 2022
Estimated Primary Completion Date January 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02852837
Other Study ID Numbers  ICMJE CR108180
54767414MMY1003 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP