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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Daratumumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02852837

CR108180

54767414MMY1003 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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50 participants in 3 patient groups

Part 1: Dose Escalation Part

Experimental group

Description:

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).

Treatment:

Drug: Daratumumab

Part 2: Pharmacokinetic (PK) Expansion Part

Experimental group

Description:

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

Treatment:

Drug: Daratumumab

Part 3: Safety Expansion Part

Experimental group

Description:

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.

Treatment:

Drug: Daratumumab