A PhaseⅠ/Ⅱ Trial of Chidamide，Decitabine and Immune Checkpoint Inhibitors in Relapsed/Refractory Non-Hodgkin Lymphoma and Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
This phase I/II trial aims to evaluate safety and efficacy of Chidamide, Decitabine and Immune checkpoint inhibitors in relapsed/refractory Non-Hodgkin Lymphoma and advanced solid tumors.
详细描述
Chidamide is a novel and orally active benzamide class of HDAC inhibitor that selectively inhibits activity of HDAC1, 2, 3 and 10, which can induce tumor-cell apoptosis, suppress cell proliferation and enhance immune surveillance. Low-dose decitabine inhibits the activity of DNA methyltransferase, which can increase the expression of tumor antigens and HLA molecules, enhance antigen processing, promote T cell infiltration, and boost effector T cell function. Immune checkpoint inhibitors (ICIs) have emerged as effective therapies for many cancers by promoting the reactivation and restoring function of T cells. In conclusion, we speculate that the chemotherapy free regimen of Chidamide, Decitabine and Immune checkpoint inhibitors may explore a new avenue for therapeutic intervention in relapsed/refractory Non-Hodgkin Lymphoma and advanced solid tumors.
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
- 16 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •16 to 80 years of age.
- •ECOG performance of less than
- •Life expectancy of at least 3 months.
- •Histopathological confirmed Non-Hodgkin Lymphoma and solid tumors.
- •Patients are relapsed/refractory Non-Hodgkin Lymphoma with ineligible for autologous hematopoietic stem cell transplantation.
- •The guidelines（ASCO/CSCO）recommend patients to participate in clinical trials.
- •Subjects must have at least one measureable target lesion.
- •Willingness to provide written informed consent for the study.
排除标准
- •Active, known or suspected autoimmune diseases.
- •Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
- •History of severe hypersensitive reactions to other monoclonal antibodies.
- •History of allergy or intolerance to study drug components.
- •Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
- •History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.
- •Uncontrolled intercurrent illness, including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
- •History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
- •Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.
- •Vaccination within 30 days of study enrollment.
- •Active bleeding or known hemorrhagic tendency.
研究组 & 干预措施
Experimental arm
Drug: Chidamide10mg/day, day1-4; 20mg/day, day8, 11, 15, 18. Drug: Decitabine10mg/day, day1-5. Drug: Immune Checkpoint Inhibitors（anti-PD1/PD-L1/CTLA4 antibodies）. Physicians will decide which ICIs will be used during treatment.
Every 3 weeks.
干预措施: Chidamide (Drug)
Experimental arm
Drug: Chidamide10mg/day, day1-4; 20mg/day, day8, 11, 15, 18. Drug: Decitabine10mg/day, day1-5. Drug: Immune Checkpoint Inhibitors（anti-PD1/PD-L1/CTLA4 antibodies）. Physicians will decide which ICIs will be used during treatment.
Every 3 weeks.
干预措施: Decitabine (Drug)
Experimental arm
Drug: Chidamide10mg/day, day1-4; 20mg/day, day8, 11, 15, 18. Drug: Decitabine10mg/day, day1-5. Drug: Immune Checkpoint Inhibitors（anti-PD1/PD-L1/CTLA4 antibodies）. Physicians will decide which ICIs will be used during treatment.
Every 3 weeks.
干预措施: Immune checkpoint inhibitors（anti-PD1/PD-L1/CTLA4 antibodies） (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: 3 years
The percentage of patients with CR or PR was determined according to the revised lymphoma efficacy evaluation criteria (Lugano 2014 criteria) and Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Adverse events
时间窗: 3 years
Incidence, nature, and severity of adverse events are graded according to the National Cancer Institute Common Terminology Criteria for adverse events (version5.0).
次要结局
- Duration of response (DOR)(3 years)
- Progression-free survival (PFS)(3 years)
研究者
Han weidong
Professor
Chinese PLA General Hospital