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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 主要终点
- Area Under the Plasma Concentration-Time Curve (AUC) (Part 1 and 2)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
- •Received anti-myeloma treatment within 2 weeks before Cycle 1, Day 1
研究组 & 干预措施
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).
干预措施: Daratumumab (Drug)
Part 2: Pharmacokinetic (PK) Expansion Part
Participants will receive daratumumab at 16 mg/kg in 3 periods as given in the Part 1.
干预措施: Daratumumab (Drug)
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.
干预措施: Daratumumab (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve (AUC) (Part 1 and 2)
时间窗: 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.
Elimination Half-Life (t1/2) (Part 1 and 2)
时间窗: 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).
Trough Analyte Concentration (Ctrough) (Part 1 and 2)
时间窗: 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.
Volume of Distribution (Vd) (Part 1 and 2)
时间窗: 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.
Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability (Part 1,2 and 3)
时间窗: 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)
时间窗: 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.
Systemic Clearance (CL) (Part 1 and 2)
时间窗: 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 \[0-infinity\]).
次要结局
- Number of Participants With Incidence of Antibodies to Daratumumab(Up to Follow-up Phase-Week 8)
- Time to Response(From the date of first dose of daratumumab to the date of initial documentation of a response (approximately 2 years))
- Overall Response Rate (ORR)(From the date of first dose of daratumumab to the date of initial documentation of 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))
- 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))