A Phase Ib/II Clinical Trial of Linperlisib Combined With Camrelizumab and Pegaspargase in Advanced or Relapsed/Refractory NK/T-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- The best objective response rate（ORR） over 6 treatment cycles
研究概览
简要总结
The patients diagnosed with relapsed/refractory or advanced NK/T-cell Lymphoma (r/r NKTCL) were selected as the research objects. To explore effective and safe treatment for advanced or r/r NKTCL, the combination of PI3K-δ inhibitor Linperlisib with PD-1 blockade Camrelizumab and anti-metabolic agent Pegaspargase was applied for the treatment.
详细描述
This is a prospective, single-arm, single-center Ib/II clinical trial that included an initial safety run-in phase with safety monitoring before the main enrollment (expansion phase).The aim of phase Ib is to evaluate the recommended phase 2 dose and dose-limiting toxicity (DLT), and the aim of phase II study is to evaluate, for the first time, the safety and efficacy of the treatment of Linperlisib combined with PD-1 blockade Camrelizumab and Pegaspargase in patients diagnosed with advanced or r/r ENKTL, respectively.
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
- •Histopathology and immunohistochemistry confirmed diagnosis of ENKTL according to WHO 2016 criteria.
- •refractory or relapsed after initial remission, or Ann-Arbor stage III-IV de novo patients
- •PET/CT or CT/MRI with at least one objectively evaluable lesion.
- •Expected to survive more than 3 months.
- •General status ECOG score 0-2 points.
- •The laboratory test within 1 week before enrollment meets the following conditions:
- •Blood routine: WBC≥3×10e9/L, PLT≥75×10e9/L, ANC≥1.5×10e9/L. sCR≤1.5 mg/dL,GFR≥50 ml/min. Liver function: ALT & AST≤3 times the upper limit of normal, TBIL ≤2 times the upper limit of normal.
- •Serum fibrinogen level≥1.0 g/L.
- •Sign the informed consent form
排除标准
- •Patients with CNS involvement, or with other neoplasm;
- •Patients has received PI3K inhibitor treatment before enrollment
- •Poor performance status, ECOG≥2;
- •Patients in lactation or pregnancy；
- •Patients (male or female) have the possibility of childbirth but are unwilling or have not taken effective contraceptive measures；
- •Patients allergic to any of the study drugs；
- •Patients with active infection；
- •Patients with a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
- •Patients with a history of interstitial pneumonia, non infectious pneumonia, or highly suspected interstitial pneumonia;
- •Patients with a history of neurological or psychiatric disorders, including epilepsy or dementia, in the past
- •According to the researcher's judgment, there are accompanying diseases that seriously endanger patient safety or affect patient completion of the study.
研究组 & 干预措施
treatment arm
Linperlisib:
Phase Ib：oral, 80 mg/d, QD; Phase II： oral, RP2D, QD.
Camrelizumab for Injection:
Phase Ib & Phase II：intravenous drip, 200 mg/d, Q3W, administered on day 1 of each cycle (3 weeks in each cycle)
Pegaspargase:
Phase Ib & Phase II：intramuscular injection，2500 IU/m2, Q3W, administered on day 1 of each cycle (3 weeks in each cycle)
干预措施: Linperlisib (Drug)
treatment arm
Linperlisib:
Phase Ib：oral, 80 mg/d, QD; Phase II： oral, RP2D, QD.
Camrelizumab for Injection:
Phase Ib & Phase II：intravenous drip, 200 mg/d, Q3W, administered on day 1 of each cycle (3 weeks in each cycle)
Pegaspargase:
Phase Ib & Phase II：intramuscular injection，2500 IU/m2, Q3W, administered on day 1 of each cycle (3 weeks in each cycle)
干预措施: Camrelizumab (Drug)
treatment arm
Linperlisib:
Phase Ib：oral, 80 mg/d, QD; Phase II： oral, RP2D, QD.
Camrelizumab for Injection:
Phase Ib & Phase II：intravenous drip, 200 mg/d, Q3W, administered on day 1 of each cycle (3 weeks in each cycle)
Pegaspargase:
Phase Ib & Phase II：intramuscular injection，2500 IU/m2, Q3W, administered on day 1 of each cycle (3 weeks in each cycle)
干预措施: Pegaspargase (Drug)
treatment arm
Linperlisib:
Phase Ib：oral, 80 mg/d, QD; Phase II： oral, RP2D, QD.
Camrelizumab for Injection:
Phase Ib & Phase II：intravenous drip, 200 mg/d, Q3W, administered on day 1 of each cycle (3 weeks in each cycle)
Pegaspargase:
Phase Ib & Phase II：intramuscular injection，2500 IU/m2, Q3W, administered on day 1 of each cycle (3 weeks in each cycle)
干预措施: Dexamethasone (Drug)
结局指标
主要结局
The best objective response rate（ORR） over 6 treatment cycles
时间窗: Within 6 treatment cycles (each cycle is 21 days)
Overall response rate means sum of complete response rate and partial response rate
次要结局
- Progression Free Survival (PFS)(From date of enrollment until the date of progression or date of death from any cause, whichever came first, assesed up to 2 years.)
- Disease Control Rate（DCR）(Up to 2 years after enrollment.)
- Objective Response Rate（ORR）(At the end of 2nd, 4th, 6th treatment cycles,respectively (each cycle is 21 days))
- Overall Survival (OS)(From date of enrollment until the date of documented death from any cause or follow up, whichever came first, assesed up to 2 years.)
- Complete Response （CR）(At the end of 2nd, 4th, 6th treatment cycles,respectively (each cycle is 21 days))
研究者
LIANG WANG
Director of the department of hematology
Beijing Tongren Hospital