Chidamide Plus Post-transplantation Cyclophosphamide and Cyclosporine to Prevent Graft-versus-host Disease After Myeloablative Conditioning, Matched Peripheral-blood Stem-cell Transplantation
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- aGVHD
研究概览
简要总结
This study is to explore the efficacy and safety of introduction of chidamide in PTCy based GVHD prophylaxis in patients undergoing allogeneic PBSCT.
详细描述
Eligible patients were aged 16 to 65 years, diagnosed with hematologic malignancy, and had a Karnofsky performance score of ≥70% and were candidates for myeloablative HCT. A 8/8 HLA allelic match between the donor and the recipient at HLA-A, HLA-B, HLA-C, and HLA-DRB1 by high-resolution typing was required. The graft source was PBSC.
Patients received a myeloablative conditioning regimen consisting of oral chidamide given twice weekly at a dose of 20 mg from day -7 to 2 weeks post transplantation, intravenous busulfan 3.2 mg/kg from day -6 to -3, intravenous fludarabine 30 mg/m2 and cytarabine 1g/m2 respectively from day -6 to -2. PBSCs were infused on day 0. GVHD prophylaxis was post-transplantation cyclophosphamide (50 mg/kg on day +3, +4) and cyclosporine (started from day +5). In the absence of GVHD, cyclosporine tapering started on day +100 and discontinued on day +180. Minimal residual disease (MRD) was determined by multi-parameter flow cytometry.
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 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 16 years or older, and ≤ 65 years at time of enrollment
- •Signed informed consent
- •Hematologic disorder requiring allogeneic hematopoietic cell transplantation
- •Left ventricular ejection fraction (LVEF) ≥ 45% by multiple uptake gated acquisition (MUGA) scan or echocardiogram
- •Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusing lung capacity oxygenation (DLCO) adjusted ≥ 50% of predicted values on pulmonary function tests
- •Transaminases (AST, ALT) < 3 times upper limit of normal (ULN) values
- •Creatinine clearance calculated ≥ 50 mL/min
- •Karnofsky Performance Status Score ≥ 60%.
- •Human leukocyte antigen (HLA) matched 8/ (A, B, C, DRB1) related or unrelated donor
排除标准
- •Active infection not controlled with appropriate antimicrobial therapy HIV, hepatitis B (HBcAb positive but HBsAg negative with undetectable viral load are eligible), or hepatitis C infection
- •Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) ≥4
- •Anti-thymocyte globulin (ATG) as part of the conditioning regimen
- •Histone deacetylase (HDAC), DAC, HSP90 inhibitors or valproic acid for the treatment of cancer within 30 days
- •Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first chidamide treatment
- •Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: Any history of ventricular fibrillation or torsade de pointes; Bradycardia defined as heart rate (HR)< 45 bpm (Patients with pacemakers are eligible if HR ≥ 45 bpm); Screening electrocardiogram (ECG) with a QTcF > 480 msec; Right bundle branch block + left anterior hemiblock (bifascicular block); Patients with myocardial infarction or unstable angina ≤ 12 months prior to starting study drug; Other clinically significant heart disease (e.g., New York Heart Association (NYHA) class III or IV , uncontrolled hypertension) as per discretion of principal investigator and/or treating physician; Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug with the exception of drugs listed on Appendix B of study documents that are required for hematopoietic cell transplantation (HCT) patients.
研究组 & 干预措施
Chidamide
Chidamide, tablets, 5 mg/tablet, 20 mg orally twice weekly from D-7~+14 Cyclophosphamide: 50 mg/Kg intravenously D+3, +4 Cyclosporine A: intravenously then orally 3 mg/Kg D+5~D+100
干预措施: Chidamide (Drug)
Chidamide
Chidamide, tablets, 5 mg/tablet, 20 mg orally twice weekly from D-7~+14 Cyclophosphamide: 50 mg/Kg intravenously D+3, +4 Cyclosporine A: intravenously then orally 3 mg/Kg D+5~D+100
干预措施: Cyclophosphamide (Drug)
Chidamide
Chidamide, tablets, 5 mg/tablet, 20 mg orally twice weekly from D-7~+14 Cyclophosphamide: 50 mg/Kg intravenously D+3, +4 Cyclosporine A: intravenously then orally 3 mg/Kg D+5~D+100
干预措施: cyclosporine A (Drug)
结局指标
主要结局
aGVHD
时间窗: 100 day after infusion of PBSCs
accumulated incidence of aGVHD
次要结局
- GRFS(3 years after recruitment)
- DFS(3 years after recruitment)
- OS(3 years after recruitment)
- cGVHD(2 yeas after infusion of PBSCs)
研究者
Jie Ji
MD
Sichuan University