A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 92
- 试验地点
- 11
- 主要终点
- The Clinical Benefit Response (CBR)
研究概览
简要总结
The primary objective of this study is to determine the efficacy of PCI-32765, both as a single agent and in combination with dexamethasone, in subjects with relapsed or relapsed and refractory Multiple Myeloma (MM)
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 clinical trials. The current study is designed and intended to determine the effects of PCI-32765 in subjects with 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
- •Diagnosis of symptomatic MM with measurable disease, defined here as having at least one of the following:
- •Serum monoclonal protein (M-protein) ≥0.5 g/dL as determined by serum protein electrophoresis (SPEP)
- •Urine M-protein ≥200 mg/24 hrs
- •Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal
- •Relapsed or relapsed and refractory MM after receiving at least 2 but no more than 5 previous lines of therapy, 1 of which must be an immunomodulator.
- •Refractory myeloma (to most recent treatment) is defined as disease that is nonresponsive while on treatment or progressive disease within 60 days after the completion of preceding treatment. Nonresponsive disease is defined as either failure to achieve minimal response or development of progressive disease while on therapy.
- •Men and women ≥18 years of age.
- •ECOG performance status of ≤ 1.
排除标准
- •Subject must not have primary refractory disease defined as disease that is nonresponsive in subjects who have never achieved a minor response (MR) or better with any therapy.
- •Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome, osteosclerotic myeloma, or Crow-Fukase syndrome.
- •Plasma cell leukemia.
- •Primary amyloidosis.
- •Certain exclusions on prior therapy.
- •ANC <0.75 x 10^9/L independent of growth factor support.
- •Platelets <50 x 10^9/L) independent of transfusion support.
- •AST or ALT ≥3.0 x upper limit of normal (ULN).
- •Total bilirubin >2.5 x ULN, unless due to Gilbert's syndrome.
- •Creatinine >2.5 mg/dL.
- •Unable to swallow capsules or disease significantly affecting gastrointestinal function.
- •Requires anti-coagulation with warfarin or a vitamin K antagonist. Requires treatment with strong CYP3A4/5 inhibitors.
研究组 & 干预措施
Cohort 1
PCI-32765 420 mg per day
干预措施: PCI-32765 (Drug)
Cohort 2
PCI-32765 560 mg per day, 40 mg dexamethasone (oral) once per week
干预措施: PCI-32765 (Drug)
Cohort 2
PCI-32765 560 mg per day, 40 mg dexamethasone (oral) once per week
干预措施: Dexamethasone (Drug)
Cohort 3
PCI-32765 840 mg per day
干预措施: PCI-32765 (Drug)
Cohort 4
PCI-32765 840 mg per day, 40 mg dexamethasone (oral) once per week
干预措施: PCI-32765 (Drug)
Cohort 4
PCI-32765 840 mg per day, 40 mg dexamethasone (oral) once per week
干预措施: Dexamethasone (Drug)
结局指标
主要结局
The Clinical Benefit Response (CBR)
时间窗: From the date of first study treatment until disease progression per IMWG, up to 60 months
The clinical benefit response (CBR) rate, defined as the proportion of subjects who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or minimal response (MR) as assessed by the modified International Myeloma Working Group (IMWG) response criteria
次要结局
- Pharmacokinetics (PK). (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Maximum Observed Plasma Concentration (Cmax)(Procedure was performed up to 60 weeks.)
- Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Time to Maximum Observed Plasma Concentration (Tmax).(Procedure was performed up to 60 weeks.)
- Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h).(Procedure was performed up to 60 weeks.)
- Duration of Clinical Benefit Response (DCB)(From the date of first study treatment until disease progression per IMWG, up to 60 months)
- Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Terminal Elimination Half-life (t1/2,Term).(Procedure was performed up to 60 weeks.)
- Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Metabolite-to-Parent Ratio for AUC0-24h (M/P AUC0-24h)(Procedure was performed up to 60 weeks.)
- To Evaluate the Efficacy of PCI-32765 by Assessing ORR(From the date of first study treatment until disease progression per IMWG, up to 60 months)
- Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Accumulation Ratio for AUC0-24h (Acc. Ratio AUC0-24h)(Procedure was performed up to 60 weeks.)
- Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Metabolite-to-Parent Ratio for Cmax (M/P Cmax)(Procedure was performed up to 60 weeks.)
- Duration of Response (DOR)(up to 3 Years)