A Phase 2, Randomized, Blinded, Placebo-controlled, Multicenter Study of Siltuximab (Anti IL 6 Monoclonal Antibody) in Subjects With High-risk Smoldering Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 85
- 主要终点
- One-Year Progression-Free Survival (PFS) Rate
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of siltuximab compared with placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) in patients with high-risk smoldering multiple myeloma (SMM).
详细描述
This is a randomized (treatment assigned by chance), double-blind (neither patient nor investigator know which treatment is given), multicenter study to evaluate the safety and efficacy of siltuximab compared with placebo in patients with high-risk SMM (defined as bone marrow plasma cells >=10% and either serum monoclonal protein >=3 g/dL, or abnormal free light chain ratio <0.126 or >8 and serum M-protein <3 g/dL but >=1 g/dL). Approximately 74 patients will receive either siltuximab or placebo by intravenous (IV, injection into a vein) infusion every 4 weeks until progression to symptomatic multiple myeloma, unacceptable toxicity, withdrawal of consent, or the end of the study (approximately 4 years after randomization of the last patient). Efficacy, pharmacokinetics, immunogenicity, and potential biomarkers will be assessed at time points defined in the protocol. Patient reported outcomes (European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30, Brief Pain Inventory [worst pain], Non-Chemotherapy Anemia Symptom Scale) will be administered before any procedure or treatment at each visit. Patient safety will be monitored throughout the study.
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
- Double (Participant, Investigator)
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
- •Diagnosis of smoldering multiple myeloma (SMM) for <4 years
- •Diagnosis of high-risk SMM (defined as bone marrow plasma cells >=10% and either serum monoclonal protein >=3 g/dL, or abnormal free light chain ratio <0.126 or >8 and serum M-protein <3 g/dL but >=1 g/dL)
- •Patients must be within certain limits for protocol-specified laboratory tests
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- •Women not of childbearing potential must be postmenopausal, permanently sterilized, or otherwise incapable of pregnancy
- •Women of childbearing potential must agree to use adequate birth control measures and agree to not donate eggs for the purpose of assisted reproduction during the study and for 3 months after receiving the last dose of study agent, and must have a negative pregnancy test at screening
- •Men must agree to use a double-barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study agent
排除标准
- •Having symptomatic multiple myeloma, defined by any of the following (if due to myeloma): lytic bone lesions, severe osteopenia (low bone density), pathologic fractures, hypercalcemia (too much calcium in the blood), kidney insufficiency; symptomatic hyperviscosity of the blood, or recurrent serious bacterial infections such as pneumonia
- •Primary systemic amyloid light (AL) chain amyloidosis (a build-up of amyloid light chain proteins in the blood)
- •Prior or concurrent exposure to approved or investigational multiple myeloma treatments (concurrent treatment with bone-protecting agents (eg, bisphosphonates, denosumab), or steroids (not exceeding 10 mg prednisone per day or equivalent) are only allowed if given in a stable dose and for a nonmalignant condition; concurrent treatment with erythropoietin-stimulating agents (ESAs) are not allowed.)
- •Prior exposure to agents targeting interleukin 6 (IL 6) or the IL 6 receptor
- •Other malignancy within the past 3 years, except for the following, if treated and not active: basal cell or nonmetastatic (non-spreading) squamous cell carcinoma of the skin, cervical carcinoma or International Federation of Gynecology and Obstetrics Stage 1 carcinoma of the cervix
研究组 & 干预措施
Siltuximab
Type=exact, unit=mg/kg, number=15, form=intravenous infusion, route=intravenous use, every 4 weeks until progression to symptomatic multiple myeloma, unacceptable toxicity, withdrawal of consent, or the end of the study.
干预措施: Siltuximab (Drug)
Placebo
Form=intravenous infusion, route=intravenous use route=intravenous, use every 4 weeks until progression to symptomatic multiple myeloma, unacceptable toxicity, withdrawal of consent, or the end of the study.
干预措施: Placebo (Drug)
结局指标
主要结局
One-Year Progression-Free Survival (PFS) Rate
时间窗: Up to 1 Year
One-year PFS rate is defined as the percentage (%) of participants surviving 1 year after randomization without progression to multiple myeloma or death estimated by the Kaplan-Meier method and based on the International Myeloma Working Group (IMWG) calcium, renal, anemia, and bone lesions (CRAB) criteria. Progressive disease (PD) is defined as presence of an M- component in serum plus clonal plasma cells in the bone marrow plus 1 or more of the following: Calcium elevation (greater than \[\>\] 11.5 milligram per deciliter \[mg/dL\] \[\> 2.88 millimoles per liter {mmol/L}\]); Renal insufficiency (creatinine \> 2 mg/dL \[177 micromoles per liter or more\]; Anemia (hemoglobin less than \[\<\] 10 gram per deciliter \[g/dL\] or 2 g/dL lower than lower limit of normal \[LLN\] \[hemoglobin \< 6.5 mmol/L or 1.25 mmol/L lower than LLN\]); Bone disease (lytic lesions or osteopenia).
次要结局
- Time to Worsening in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) Scale Score(Up to 4.7 Years)
- Number of Participants With Best Response to First Subsequent Multiple Myeloma Treatment(Up to 4.7 Years)
- Percentage of Participants With Serum M-protein Response(Up to 4.7 Years)
- Time to Worsening in the Brief Pain Inventory (BPI) Worst Item Scores(Up to 4.7 Years)
- Number of Participants With Symptomatic Multiple Myeloma With Adverse Prognostic Features(Up to 4.7 Years)
- Overall Survival (OS)(Up to 4.7 Years)
- Progressive Disease Indicator Rate (PDIR) at 6 Months(At 6 Months)
- Progression-Free Survival(Up to 4.7 Years)