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Multiple MyelomaPhase 1NCT02852837

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

A Phase 1 study testing Daratumumab in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 5 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Daratumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
5 sitesChina
Study dates
26 Sep 2016to 13 Dec 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

China5 sites

  • Study site

    Beijing

  • Study site

    Hangzhou

  • Study site

    Shanghai

  • Study site

    Suzhou

  • Study site

    Tianjin

Other trials in China

About this study

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

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).

Being tested
Daratumumab
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DaratumumabDrug

    Also called JNJ-54767414

    Intravenous (IV) infusion of 8 mg/kg or 16 mg/kg daratumumab.

Study groups in NCT02852837
Study groupRoleWhat they receive
Part 1: Dose Escalation PartExperimentalParticipants 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).
Receives: Drug: Daratumumab
Part 2: Pharmacokinetic (PK) Expansion PartExperimentalParticipants will receive daratumumab at 16 mg/kg in 3 periods as given in the Part 1.
Receives: Drug: Daratumumab
Part 3: Safety Expansion PartExperimentalParticipants 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.
Receives: Drug: Daratumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability (Part 1,2 and 3)

    Measured: 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)

    The Cmax is the maximum observed plasma concentration.

    Measured: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)

  3. Trough Analyte Concentration (Ctrough) (Part 1 and 2)

    The (Ctrough) is the concentration before dosing just prior to the beginning of a doing interval.

    Measured: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)

  4. Area Under the Plasma Concentration-Time Curve (AUC) (Part 1 and 2)

    AUC is defined as area under the plasma concentration-time curve.

    Measured: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)

  5. 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]).

    Measured: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)

  6. 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).

    Measured: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)

  7. 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.

    Measured: Until Cycle 14, Day 1 (each cycle of 21 days till Cycle 3 and 28 days Cycle 4 onward)

Secondary outcomes (6)

  1. 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.

    Measured: From the date of first dose of daratumumab to the date of initial documentation of progressive disease (approximately 2 years)

  2. 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).

    Measured: From the date of first dose of daratumumab to the date of initial documentation of a response (approximately 2 years)

  3. 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.

    Measured: From the date of initial documentation of a response to the date of first documented evidence of progressive disease (approximately 2 years)

  4. 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.

    Measured: From the date of first dose of daratumumab to the date of first documented progressive disease (approximately 2 years)

  5. Overall Survival (OS)

    Overall survival (OS) is measured from the date of first dose of daratumumab to the date of the participant's death.

    Measured: From the date of first dose of daratumumab to the date of the participant's death (approximately 2 years)

  6. Number of Participants With Incidence of Antibodies to Daratumumab

    Measured: Up to Follow-up Phase-Week 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2016 (estimated)
  2. Study start26 Sep 2016
  3. Primary completion13 Dec 2019
  4. Study completion13 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02852837
Sponsor's protocol ID
CR108180
Other IDs
54767414MMY1003
Status last verified
Nov 2020
First submitted
29 Jul 2016
Last updated
16 Nov 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 37022569

  • 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.

    PubMed 36301338

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Daratumumab in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 5 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02852837, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2020.

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