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

NCT02852837 | Completed Phase 1

• 2 other identifiers: CR10818054767414MMY1003
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (7)

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

  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)

  The Cmax is the maximum observed plasma concentration.

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

• Trough Analyte Concentration (Ctrough) (Part 1 and 2)

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

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

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

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

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

• 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 \[0-infinity\]).

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

• 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).

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

• 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.

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

Secondary Outcomes (6)

• Overall Response Rate (ORR)

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

• Time to Response

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

• Duration of Response

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

• Progression-Free Survival (PFS)

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

• Overall Survival (OS)

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

Study Arms (3)

Part 1: Dose Escalation Part

EXPERIMENTAL

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

Part 2: Pharmacokinetic (PK) Expansion Part

EXPERIMENTAL

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

Drug: Daratumumab

Part 3: Safety Expansion Part

EXPERIMENTAL

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

Interventions

Daratumumab DRUG

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

Also known as: JNJ-54767414

Part 1: Dose Escalation Part; Part 2: Pharmacokinetic (PK) Expansion Part; Part 3: Safety Expansion Part

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (5)

Unknown Facility

Beijing, China

Location

Unknown Facility

Hangzhou, China

Location

Unknown Facility

Shanghai, China

Location

Unknown Facility

Suzhou, China

Location

Unknown Facility

Tianjin, China

Location

Related Publications (2)

• 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.

  PMID: 37022569 DERIVED

• 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.

  PMID: 36301338 DERIVED

Related Links

• 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

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2016
• First Posted: August 2, 2016
• Study Start: September 26, 2016
• Primary Completion: December 13, 2019
• Study Completion: December 13, 2019
• Last Updated: November 16, 2020

Record last verified: 2020-11

Locations

CN (5)