A Multicenter Phase 1/2b Study of the Bruton's Tyrosine Kinase Inhibitor, Ibrutinib (PCI-32765), in Combination With Carfilzomib (Kyprolis™) in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 17
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
A MULTICENTER PHASE 1/2B STUDY OF THE BRUTON'S TYROSINE KINASE INHIBITOR, IBRUTINIB (PCI-32765), IN COMBINATION WITH CARFILZOMIB (KYPROLIS™) IN SUBJECTS WITH RELAPSED OR RELAPSED AND REFRACTORY MULTIPLE MYELOMA
详细描述
Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoietic cells other than T cells and is necessary for downstream signal transduction from various hematopoietic receptors including the B cell receptor as well as some Fc, chemokine, and adhesion receptors, and is crucial for both B cell development and osteoclastogenesis. Although down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from many myeloma patients and some cell lines. PCI-32765 is a potent and specific inhibitor of Btk currently in Phase 2 and 3 clinical trials. The current study is designed and intended to determine the safety and efficacy of PCI-32765 in combination with carfilzomib (Kyprolis™) with and without dexamethasone in subjects with relapsed or relapsed and refractory multiple myeloma (MM).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Measurable disease of MM as defined by at least ONE of the following:
- •Serum monoclonal protein (SPEP) ≥1 g/dL
- •Urine M-protein ≥200 mg/24 hrs
- •Serum free light chain (SFLC): involved FLC ≥10 mg/dL (≥100 mg/L) AND abnormal kappa to lambda serum free light chain ratio
- •Relapsed or relapsed and refractory MM after receiving at least 2 previous therapies, including an immunomodulator and bortezomib and had either no response or documented disease progression (according to IMWG criteria) to the most recent treatment regimen
- •Adequate hematologic, hepatic, and renal function
- •ECOG performance status of 0-2
- •Inclusion Criteria for Phase 2 Sub-study Cohort:
- •Must meet all inclusion criteria defined in main study and in addition the following criteria must be met:
- •Subject must have received a regimen containing carfilzomib in combination with dexamethasone as their most recent line of therapy and have:
- •Achieved less than a partial response (<PR) following at least 4 cycles and are without evidence of progression disease (PD).
- •Disease progression following an initial confirmed response of MR or better to the combination (according to IMWG response criteria).
排除标准
- •Subject must not have primary refractory disease
- •Plasma cell leukemia, primary amyloidosis or POEMS syndrome
- •Unable to swallow capsules or disease significantly affecting gastrointestinal function
- •Requires anti-coagulation with warfarin or a vitamin K antagonist
- •Requires treatment with strong CYP3A inhibitors
- •Exclusion Criteria for Phase 2 Sub-study Cohort:
- •Must not meet any exclusion criteria defined in main study except for exclusion criteria "Subject must not have primary refractory disease" which is related to prior carfilzomib
研究组 & 干预措施
Phase 2b - Sub-study
Ibrutinib PO 840 mg + Carfilzomib IV 20/36 mg/m2 + Dexamethasone PO 20 mg
干预措施: Dexamethasone (Drug)
Phase 1 - Dose Finding
Ibrutinib PO 560mg + Carfilzomib IV 20/27mg/m2 + Dexamethasone PO 20mg
干预措施: Ibrutinib (Drug)
Phase 1 - Dose Finding
Ibrutinib PO 560mg + Carfilzomib IV 20/27mg/m2 + Dexamethasone PO 20mg
干预措施: Carfilzomib (Drug)
Phase 1 - Dose Finding
Ibrutinib PO 560mg + Carfilzomib IV 20/27mg/m2 + Dexamethasone PO 20mg
干预措施: Dexamethasone (Drug)
Phase 2b - Main Study
Ibrutinib PO 560mg + Carfilzomib IV 20/36mg/m2 + Dexamethasone PO 20mg
干预措施: Ibrutinib (Drug)
Phase 2b - Main Study
Ibrutinib PO 560mg + Carfilzomib IV 20/36mg/m2 + Dexamethasone PO 20mg
干预措施: Carfilzomib (Drug)
Phase 2b - Main Study
Ibrutinib PO 560mg + Carfilzomib IV 20/36mg/m2 + Dexamethasone PO 20mg
干预措施: Dexamethasone (Drug)
Phase 2b - Sub-study
Ibrutinib PO 840 mg + Carfilzomib IV 20/36 mg/m2 + Dexamethasone PO 20 mg
干预措施: Ibrutinib (Drug)
Phase 2b - Sub-study
Ibrutinib PO 840 mg + Carfilzomib IV 20/36 mg/m2 + Dexamethasone PO 20 mg
干预措施: Carfilzomib (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: up to 4 years
-To evaluate the overall response (ORR) of ibrutinib in combination with carfilzomib and dexamethasone.
次要结局
- Progression Free Survival (PFS)(Up to 4 years)
- Duration of Response (DOR)(Up to 4 years)
- Overall Survival(Up to 4 years)