Phase 1/2a Study of Anti-PD-L1 Monoclonal Antibody Durvalumab in Combination With Pralatrexate and Romidepsin, Oral 5-Aza and Romidepsin, Romidepsin Alone, or Oral 5-Azacitidine for Treatment of Patients With Relapsed and Refractory PTCL
试验速览
- 阶段
- 1 期
- 入组人数
- 148
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This is an open-label, Phase 1/2a, dose-finding study with an initial phase 1 portion, articulated in four separate treatment arms, followed by a dedicated phase 2 for qualifying treatment Arm(s).
The primary objective of the Phase 1 portion is to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the combinations of: Durvalumab, oral 5-azacitidine, and romidepsin (Arm A); durvalumab, pralatrexate, and romidepsin (Arm B); durvalumab and romidepsin (Arm C); or durvalumab and oral 5-azacitidine (Arm D), in patients with peripheral T-cell lymphoma (PTCL). The safety and toxicity profile of these combinations will be evaluated throughout the entire study.
If one or more of the combinations in Arms A, B, C, or D are found to be feasible and an MTD is established, the phase 2 portion of the study will be initiated for the combination(s) with the strongest efficacy signal provided acceptable toxicity.
详细描述
The peripheral T-cell lymphomas (PTCL) are a heterogeneous group of aggressive lymphoid neoplasms and account for 10-15% of all newly diagnosed cases of non-Hodgkin's lymphoma (NHL). The current prevalence of PTCL in the United States is estimated to be approximately 9,500 patient. Treatment options for patients with relapsed/refractory (R/R) PTCL have been limited. This study focuses on exploring rational combinations of these T-cell active agents in an effort to develop novel treatment platforms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
A: Oral 5-azacitidine, durvalumab, romidepsin
Arm A: Patients will first undergo a 7-day lead-in phase of 5-azacitidine. 5-azacitidine will be administered orally from day 1 to day 14 (including the lead-in phase), durvalumab will be administered intravenously on day 8 and romidepsin intravenously on days 8 and 15 of a 28-day treatment cycle
干预措施: Durvalumab (Drug)
A: Oral 5-azacitidine, durvalumab, romidepsin
Arm A: Patients will first undergo a 7-day lead-in phase of 5-azacitidine. 5-azacitidine will be administered orally from day 1 to day 14 (including the lead-in phase), durvalumab will be administered intravenously on day 8 and romidepsin intravenously on days 8 and 15 of a 28-day treatment cycle
干预措施: Romidepsin (Drug)
A: Oral 5-azacitidine, durvalumab, romidepsin
Arm A: Patients will first undergo a 7-day lead-in phase of 5-azacitidine. 5-azacitidine will be administered orally from day 1 to day 14 (including the lead-in phase), durvalumab will be administered intravenously on day 8 and romidepsin intravenously on days 8 and 15 of a 28-day treatment cycle
干预措施: 5-Azacitidine (Drug)
B: durvalumab, pralatrexate, romidepsin
Arm B: Durvalumab will be administered intravenously on day 1, pralatrexate will be administered intravenously on days 1 and 15, and romidepsin will be administered intravenously on days 1 and 15. Each treatment cycle will last 28 days. All patients receiving pralatrexate will receive folic acid and vitamin B12 supplementation according to the drug package insert. Leucovorin rescue is also allowed at the dose of 15 mg orally twice daily on days 3 to 6 and 17 to 20.
干预措施: Durvalumab (Drug)
B: durvalumab, pralatrexate, romidepsin
Arm B: Durvalumab will be administered intravenously on day 1, pralatrexate will be administered intravenously on days 1 and 15, and romidepsin will be administered intravenously on days 1 and 15. Each treatment cycle will last 28 days. All patients receiving pralatrexate will receive folic acid and vitamin B12 supplementation according to the drug package insert. Leucovorin rescue is also allowed at the dose of 15 mg orally twice daily on days 3 to 6 and 17 to 20.
干预措施: Pralatrexate (Drug)
B: durvalumab, pralatrexate, romidepsin
Arm B: Durvalumab will be administered intravenously on day 1, pralatrexate will be administered intravenously on days 1 and 15, and romidepsin will be administered intravenously on days 1 and 15. Each treatment cycle will last 28 days. All patients receiving pralatrexate will receive folic acid and vitamin B12 supplementation according to the drug package insert. Leucovorin rescue is also allowed at the dose of 15 mg orally twice daily on days 3 to 6 and 17 to 20.
干预措施: Romidepsin (Drug)
C: durvalumab, romidepsin
Arm C: Durvalumab will be administered intravenously on day 1 and romidepsin will be administered intravenously on days 1, 8, and 15 of a 28-day treatment cycle
干预措施: Durvalumab (Drug)
C: durvalumab, romidepsin
Arm C: Durvalumab will be administered intravenously on day 1 and romidepsin will be administered intravenously on days 1, 8, and 15 of a 28-day treatment cycle
干预措施: Romidepsin (Drug)
D: durvalumab, 5-azacitidine
Arm D: Patients will first undergo a 7-day lead-in phase of 5-azacitidine. 5-azacitidine will be administered orally from day 1 to day 14 (including the lead-in phase) and durvalumab will be administered intravenously on day 8 of a 28-day treatment cycle
干预措施: Durvalumab (Drug)
D: durvalumab, 5-azacitidine
Arm D: Patients will first undergo a 7-day lead-in phase of 5-azacitidine. 5-azacitidine will be administered orally from day 1 to day 14 (including the lead-in phase) and durvalumab will be administered intravenously on day 8 of a 28-day treatment cycle
干预措施: 5-Azacitidine (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 1 year
The highest dose of study treatment that does not cause unacceptable side effects in patients with R/R PTCL in each study arm
次要结局
- Overall Response Rate (ORR)(1 year)
- Duration of Response (DoR)(1 year)
- Progression Free Survival (PFS)(1 year)