A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 22
- 试验地点
- 9
- 主要终点
- Number of Participants With Dose-limiting Toxicities (DLTs)
研究概览
简要总结
The primary objective was to determine the maximum tolerated dose of carfilzomib given twice weekly in combination with cyclophosphamide and dexamethasone for patients with newly diagnosed multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Newly diagnosed multiple myeloma
- •Measurable disease, as defined by 1 or more of the following
- •Serum M-protein ≥ 0.5 g/dL, or
- •Urine M-protein ≥ 200 mg/24 hours, or
- •In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa lambda ( κ/λ) ratio
- •Males and females ≥ 18 years of age
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Adequate hepatic function
- •Left ventricular ejection fraction (LVEF) ≥ 40%
- •Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
- •Platelet count ≥ 50 × 10^9/L
- •Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min
排除标准
- •Planned autologous hematopoietic stem cell transplantation (HSCT) for the initial therapy of newly diagnosed multiple myeloma
- •Multiple myeloma of immunoglobulin M (IgM) subtype
- •Prior systemic treatment for multiple myeloma
- •Glucocorticoid therapy within 14 days prior to enrollment that equals or exceeds the equivalent of dexamethasone 160 mg
- •Known amyloidosis
- •Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to enrollment.
- •Known human immunodeficiency virus (HIV) seropositive, hepatitis C infection, and/or hepatitis B (subjects with hepatitis B surface antigen [SAg] or core antibody receiving and responding to antiviral therapy directed at hepatitis B are allowed)
- •Significant neuropathy (Grades ≥ 2) within 14 days prior to enrollment
- •Any other clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
研究组 & 干预措施
Carfilzomib, Cyclophosphamide and Dexamethasone (CCd)
Participants received carfilzomib, cyclophosphamide and dexamethasone for up to eight 28-day cycles, or until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
干预措施: Carfilzomib (Drug)
Carfilzomib, Cyclophosphamide and Dexamethasone (CCd)
Participants received carfilzomib, cyclophosphamide and dexamethasone for up to eight 28-day cycles, or until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
干预措施: Cyclophosphamide (Drug)
Carfilzomib, Cyclophosphamide and Dexamethasone (CCd)
Participants received carfilzomib, cyclophosphamide and dexamethasone for up to eight 28-day cycles, or until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: First cycle treatment over 28-days
The MTD is defined as the highest carfilzomib dose at which fewer than 33% of participants experience a treatment-related dose-limiting toxicity (DLT) during the first 28-day cycle. The number of participants who experienced a DLT is reported. Dose-limiting toxicities are defined as any of the following carfilzomib-related adverse events: Nonhematologic: * ≥ Grade 3 non-hematological toxicity * ≥ Grade 3 acute kidney injury (creatinine \> 3 × baseline or \> 4.0 mg/dL) lasting \> 72 hours Hematologic: * Grade 4 neutropenia (absolute neutrophil count \[ANC\] \< 0.5 × 10\^9/L) lasting for \> 7 days * Febrile neutropenia (ANC \< 1.0 × 10\^9/L with a fever ≥ 38.3ºC) of any duration * Grade 4 thrombocytopenia (\< 25 × 10\^9/L) that persists for \> 14 days, despite holding treatment * Grade 3 or 4 thrombocytopenia associated with \> Grade 1 bleeding
次要结局
- Overall Response Rate (ORR)(Disease response was assessed at the end of each cycle and 30 days after the last treatment; maximum treatment duration was 32 weeks.)
- Time To Response (TTR)(Disease response was assessed at the end of each cycle and 30 days after the last treatment; maximum treatment duration was 32 weeks.)
- Number of Participants With Adverse Events(From first dose of study drug until 30 days after last dose; median duration of treatment was 31 weeks.)