A Phase Ib Combination Study of Rituximab, TinostamustinEAnd CHeckpoint Inhibition With Pembrolizumab in Relapsed/Refractory DLBCL - REACH
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
Safety run-in (part 1): Relapsed or refractory B-cell Non-Hodgkin lymphoma (NHL)
Main study (part 2): Relapsed or refractory diffuse large B-cell lymphoma
详细描述
The primary objective of the safety run-in phase (part 1) is to assess the safety and tolerability of pembrolizumab in combination with R-tinostamustineand to recommend a safe and tolerated dose of tinostamustinefor use in combination with 200mg pembrolizumab and 375mg/m2 rituximab Q3W in the main efficacy part of the study (part 2).
Part 2 (main study) The primary objective of part 2 is to assess efficacy of pembrolizumab in combination with R-tinostamustineas determined by the best overall response rate (ORR) in subjects with r/r DLBCL.
Hypothesis: The combination of pembrolizumab and R-tinostamustinewill act synergistically and show high anti-tumour efficacy in subjects with r/r DLBCL. R-EDO-S101 will increase pembrolizumab-mediated anti-tumour immunity by (A) tumour de-bulking with improved access of immune cells into the tumour and reduced burden of tumour sub-clones and (B) epigenetic priming of PD-1 inhibition through the histone deacetylase inhibitor (HDACi) component of tinostamustine.
Secondary Objectives & Hypotheses
- Objective: Safety and tolerability of pembrolizumab in combination with R-tinostamustine.
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
- 是
入选标准
- •Histologically proven CD20+ DLBCL (including transformed lymphoma)
- •Previous treatment with at least 1 line of standard therapy
- •Age 18 or over
- •ECOG performance status 0/1 Measurable disease on cross-sectional imaging that is at least 1.5 cm in the longest diameter and measureable in two perpendicular dimensions
- •Adequate organ function
- •Resolution of prior systemic therapy related non-haematological AEs to grade (G) ≤
- •Participants with ≤ G 2 neuropathy may be eligible.
- •Consent to provide fresh tumour tissue during screening and treatment
排除标准
- •CNS or leptomeningeal involvement
- •Autologous stem cell transplant (ASCT) within 12 weeks or other anticancer treatment within 3 weeks of commencing therapy
- •Prior allogeneic transplant
- •Known HIV, or active Hepatitis B/C infection
- •Active systemic autoimmune disease
- •No previous therapy with agents targeting immune checkpoint proteins
研究组 & 干预措施
Safety Run in & Main Efficacy Part
Part 1 (safety run-in) aims to evaluate the maximum tolerated dose (MTD) of tinostamustinein combination with pembrolizumab (200mg Q3W) and rituximab (375mg/m2 Q3W). The dose of tinostamustineestablished to be safe and tolerable in this combination will be used in part 2 of the trial (main efficacy part).
The aim of part 2 is to detect signals of anti-tumour activity and to further assess the safety of this combination treatment in r/r DLBCL. The study has a strong focus on correlative research in order to identify mechanisms of response and resistance to pembrolizumab and the pembrolizumab/R-tinostamustinecombination.
干预措施: Tinostamustinein (Drug)
Safety Run in & Main Efficacy Part
Part 1 (safety run-in) aims to evaluate the maximum tolerated dose (MTD) of tinostamustinein combination with pembrolizumab (200mg Q3W) and rituximab (375mg/m2 Q3W). The dose of tinostamustineestablished to be safe and tolerable in this combination will be used in part 2 of the trial (main efficacy part).
The aim of part 2 is to detect signals of anti-tumour activity and to further assess the safety of this combination treatment in r/r DLBCL. The study has a strong focus on correlative research in order to identify mechanisms of response and resistance to pembrolizumab and the pembrolizumab/R-tinostamustinecombination.
干预措施: Pembrolizumab (Drug)
Safety Run in & Main Efficacy Part
Part 1 (safety run-in) aims to evaluate the maximum tolerated dose (MTD) of tinostamustinein combination with pembrolizumab (200mg Q3W) and rituximab (375mg/m2 Q3W). The dose of tinostamustineestablished to be safe and tolerable in this combination will be used in part 2 of the trial (main efficacy part).
The aim of part 2 is to detect signals of anti-tumour activity and to further assess the safety of this combination treatment in r/r DLBCL. The study has a strong focus on correlative research in order to identify mechanisms of response and resistance to pembrolizumab and the pembrolizumab/R-tinostamustinecombination.
干预措施: Rituximab (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: 2.3 years
Part 1 (safety run-in): To assess the safety and tolerability of pembrolizumab in combination with R-tinostamustineand to recommend a safe and tolerated dose of tinostamustinefor use in part 2 in combination with 200mg pembrolizumab and 375mg/m2 rituximab . Part 2 (main study): To assess efficacy of pembrolizumab in combination with R-tinostamustineas determined by best overall response in subjects with relapsed/refractory (r/r) DLBCL.
次要结局
- Secondary Objectives(2.3 years)