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

NCT ID: NCT02852837

Last Updated: 2020-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-26
• Study Completion Date: 2019-12-13

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).

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Daratumumab

Intervention Type: DRUG

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

Part 2: Pharmacokinetic (PK) Expansion Part

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

Group Type: EXPERIMENTAL

Daratumumab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Daratumumab

Intervention Type: DRUG

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

Interventions

Daratumumab

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

Intervention Type: DRUG

Other Intervention Names

JNJ-54767414

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Beijing, , China

Hangzhou, , China

Shanghai, , China

Suzhou, , China

Tianjin, , China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 37022569 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36301338 (View on PubMed)

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR108180&attachmentIdentifier=73dbcc08-6b56-4322-a2db-6ec64f3e2398&fileName=CR108180_CSR_Synopsis.pdf&versionIdentifier=

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

Other Identifiers

54767414MMY1003

Identifier Type: OTHER

Identifier Source: secondary_id

CR108180

Identifier Type: -

Identifier Source: org_study_id