Phase 1 Study to Evaluate the Tolerance and Pharmacokinetics of SHR1459 in Patients With Recurrentreplased/Refractory Mature B Cell Neoplasms Tumor
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability])
研究概览
简要总结
SHR1459 is a selective small molecule BTK inhibitor developed by Jiangsu Hengrui medicine Limited, by inhibiting the phosphorylation of BTK and down regulation of BCR signal transduction pathway, And then selectively inhibit the proliferation and migration of B cell tumor.
详细描述
SHR1459 is a selective small molecule BTK inhibitor developed by Jiangsu Hengrui medicine Limited, by inhibiting the phosphorylation of BTK and down regulation of BCR signal transduction pathway, And then selectively inhibit the proliferation and migration of B cell tumor. The objective of this phase 1 study is to evaluate the safety and tolerance of SHR1459 in patients with replaced/refractory mature B cell neoplasms, in order to determine the maximum tolerated dose (MTD) and recommended dose for phase 2 clinical study (RP2D);
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ECOG Performance Status [PS] score must be 0 or 1;
- •Life expectancy ≥ 12 weeks;
- •Mature B cell eoplasmss with histological or cytological diagnosis, including diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) , chronic lymphocytic leukemia/Small lymphocytic lymphoma (CLL/SLL), Mantle cell lymphoma (MCL), Marginal zone lymphoma (MZL) and waldenstrom macroglobulinemia (WM);
- •The function of bone marrow is basically normal;
- •Renal function is basically normal;
- •Hepatic function is basically normal.
排除标准
- •Had received treatment with the compound of the same mechanism (BTK inhibitor);
- •With infiltration of lymphoma central nervous system;
- •Received autologous stem cell transplantation within 60 days before signing the informed consent, received allogeneic stem cell transplantation in 90 days (after allogeneic stem cell transplantation, if graft-versus-host disease appeared, it must be ≤ level 1, and if there was no prohibited medication, the screening could be performed);
研究组 & 干预措施
SHR1459
Oral administration, once a day, 28 days for a cycle, until the disease progression or the intolerable toxicity occurs.
干预措施: SHR1459 (Drug)
结局指标
主要结局
Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability])
时间窗: through study completion, an average of about 6 months
The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of SHR1459 will be assessed
Recommended phase 2 dose (RP2D)
时间窗: 28 days since the date of first dose
Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) will be established according to the incidence of dose-limiting toxicities (DLTs) of escalated doses of SHR1459
次要结局
- Halflife (T1/2)(Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle))
- Apparent volume of distribution, steady state/bioavailability (Vss/F)(Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle))
- Duration of Response (DoR)(every 8 weeks through study completion, an average of about 6 months)
- Area under curve (AUC)(Day 1 and Day 2 of the single dose)
- Maximum plasma concentration, steady state (Cmax,ss)(Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle))
- Time to peak, steady state (Tmax,ss)(Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle))
- Time to Response (TTR)(every 8 weeks through study completion, an average of about 6 months)
- Progression-free survival (PFS)(every 8 weeks through study completion, an average of about 6 months)
- Time to peak (Tmax)(Day 1 and Day 2 of the single dose)
- Maximum plasma concentration (Cmax)(Day 1 and Day 2 of the single dose)
- Clearance/ bioavailability (CL/F)(Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle))
- apparent volume of distribution/bioavailability (Vd/F)(Day 1 and Day 2 of the single dose)
- Area under curve, steady state (AUCss)(Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle))
- Objective response rate (ORR)(every 8 weeks through study completion, an average of about 6 months)
- Accumulation index (Rac)(Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle))