A Randomized, Controlled, Open-Label Phase 3 Study of Melflufen in Combination With Daratumumab Compared With Daratumumab in Patients With Relapsed or Relapsed-Refractory Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 54
- 试验地点
- 26
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with Relapsed-Refractory Multiple Myeloma (RRMM) who were either double refractory to an Immunomodulatory Drug (IMiD) and a Proteasome Inhibitor (PI) (regardless of the number of prior lines of therapy), or had received at least 3 prior lines of therapy including an IMiD and a PI.
Patients received treatment with melflufen+dexamethasone+daratumumab or daratumumab until documented progressive disease, unacceptable toxicity, or patient/treating physician decision. Patients in the daratumumab treatment arm had the option to receive treatment with melflufen+dexamethasone+daratumumab after confirmed progressive disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Independent Review Committee was planned to be blinded to treatment assignment. Due to the early termination, the response assessments were only done by investigators, not by an independent review committee.
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
- •A prior diagnosis of multiple myeloma with documented disease progression after the last line of therapy
- •Double refractory to an IMiD and a PI (regardless of the number of prior lines of therapy) or have received at least 3 prior lines of therapy including an IMiD and a PI
- •Prior treatment with daratumumab or another anti-CD38 antibody may be allowed under certain circumstances:
- •Achieved at least partial response (PR) and not refractory to an anti-CD38 antibody
- •At least 6 months since the last dose of anti-CD38 antibody
- •Not discontinued anti-CD38 antibody treatment due to related Grade ≥ 3 toxicity
- •Male and female of childbearing potential agree to use contraception during the treatment period and at least 3 months after the last dose
排除标准
- •Primary refractory disease (i.e., never responded with at least Minimal Response to any prior therapy for multiple myeloma)
- •Prior treatment with CD38 CAR-T cell therapy or CD38/CD3 bispecific antibodies
- •Any medical condition that may interfere with safety or participation in this study
- •Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast, or very low and low-risk prostate cancer in active surveillance
- •Known or suspected amyloidosis, plasma cell leukemia, or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- •Known central nervous system (CNS) or meningeal involvement of myeloma
- •Prior stem cell transplant (autologous and/or allogenic) within 6 months of initiation of therapy or prior allogeneic stem cell transplantation with active graft-versus-host-disease
- •Prior treatment with melflufen
研究组 & 干预措施
Arm A (melflufen+dexamethasone+daratumumab)
Treatment was given in 28-day cycles in an outpatient treatment setting.
- Melflufen 30 mg intravenous (i.v.) infusion on Day 1 of each cycle
- Dexamethasone 40 mg per oral (p.o.) weekly (20 mg p.o. weekly if ≥75 years)
- Daratumumab 1800 mg subcutaneously (s.c.) on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7
干预措施: Melflufen (Drug)
Arm A (melflufen+dexamethasone+daratumumab)
Treatment was given in 28-day cycles in an outpatient treatment setting.
- Melflufen 30 mg intravenous (i.v.) infusion on Day 1 of each cycle
- Dexamethasone 40 mg per oral (p.o.) weekly (20 mg p.o. weekly if ≥75 years)
- Daratumumab 1800 mg subcutaneously (s.c.) on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7
干预措施: Dexamethasone (Drug)
Arm A (melflufen+dexamethasone+daratumumab)
Treatment was given in 28-day cycles in an outpatient treatment setting.
- Melflufen 30 mg intravenous (i.v.) infusion on Day 1 of each cycle
- Dexamethasone 40 mg per oral (p.o.) weekly (20 mg p.o. weekly if ≥75 years)
- Daratumumab 1800 mg subcutaneously (s.c.) on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7
干预措施: Daratumumab (Drug)
Arm B (daratumumab)
Treatment was given in 28-day cycles in an outpatient treatment setting.
• Daratumumab 1800 mg s.c. on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7
干预措施: Daratumumab (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: From the date of randomization until the end of study (approximately 12 months).
Time from the date of randomization to the date of first documentation of confirmed progressive disease (PD) or death due to any cause, whichever occurred first.
次要结局
- Overall Response Rate (ORR)(From the date of randomization until the end of study (approximately 12 months).)
- Duration of Response (DOR)(From the date of randomization until the end of study (approximately 12 months).)
- Overall Survival (OS)(From the date of randomization until the end of study (approximately 12 months).)
- Time to Response (TTR)(From the date of randomization until the end of study (approximately 12 months).)
- Best Response(From the date of randomization until the end of study (approximately 12 months).)
- Clinical Benefit Rate (CBR)(From the date of randomization until the end of study (approximately 12 months).)
- Duration of Clinical Benefit (DOCB)(From the date of randomization until the end of study (approximately 12 months).)
- Time to Progression (TTP)(From the date of randomization until the end of study (approximately 12 months).)
- Time to Next Treatment (TTNT)(From the date of randomization until the end of study (approximately 12 months).)