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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 : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Daratumumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 26, 2016
Estimated Primary Completion Date : January 13, 2020
Estimated Study Completion Date : January 13, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Daratumumab

Arm Intervention/treatment
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).
Drug: Daratumumab
Intravenous (IV) infusion of 8 mg/kg or 16 mg/kg daratumumab.
Other Name: JNJ-54767414

Experimental: Part 2: Pharmacokinetic (PK) Expansion Part
Participants will receive daratumumab at 16 mg/kg in 3 periods as given in the Part 1.
Drug: Daratumumab
Intravenous (IV) infusion of 8 mg/kg or 16 mg/kg daratumumab.
Other Name: JNJ-54767414

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.
Drug: Daratumumab
Intravenous (IV) infusion of 8 mg/kg or 16 mg/kg daratumumab.
Other Name: JNJ-54767414




Primary Outcome Measures :
  1. 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) ]
  2. 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.

  3. 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.

  4. 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.

  5. 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]).

  6. 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).

  7. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 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.

  6. Number of Participants With Incidence of Antibodies to Daratumumab [ Time Frame: Up to Follow-up Phase-Week 8 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02852837


Locations
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China
Beijing, China
Hangzhou, China
Shanghai, China
Suzhou, China
Tianjin, China, China
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02852837     History of Changes
Other Study ID Numbers: CR108180
54767414MMY1003 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: August 2, 2016    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Daratumumab
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs