A Phase II Trial Evaluating the Use of a Histone Deacetylase Inhibitor Panobinostat for Graft Versus Host Disease (GVHD) Prevention
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Number of Participants Stratified by Acute Graft Versus Host Disease GVHD Stage
研究概览
简要总结
This study will test PANO in combination with tacrolimus/sirolimus (TAC/SIR) for acute GVHD prevention. The purpose of this study is to determine if Panobinostat (PANO) when used in combination with sirolimus and tacrolimus will help reduce the incidence of Graft-vs-host disease (GVHD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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
- •Age ≥ 18 years or older 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 8/8 (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
- •Sorror's co-morbidity factors with total score >
- •Important modification to co-morbidity index calculation: DLCO adjusted will not be included in assessment of pulmonary risk, except those patients with DLCO adjusted < 50% who are excluded from the trial.
- •Anti-thymocyte globulin (ATG) as part of the conditioning regimen
- •Cyclophosphamide as part of the conditioning regimen or for GVHD prophylaxis
- •Pregnancy
- •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 PANO 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
Panobinostat (PANO) Therapy
Participants will be treated with standard of care chemotherapy agents prior to their allogeneic hematopoietic cell transplant. For Graft Versus Host Disease (GVHD) prevention, participants will receive PANO, Sirolimus and Tacrolimus.
干预措施: Panobinostat (Drug)
Panobinostat (PANO) Therapy
Participants will be treated with standard of care chemotherapy agents prior to their allogeneic hematopoietic cell transplant. For Graft Versus Host Disease (GVHD) prevention, participants will receive PANO, Sirolimus and Tacrolimus.
干预措施: Sirolimus (Drug)
Panobinostat (PANO) Therapy
Participants will be treated with standard of care chemotherapy agents prior to their allogeneic hematopoietic cell transplant. For Graft Versus Host Disease (GVHD) prevention, participants will receive PANO, Sirolimus and Tacrolimus.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Number of Participants Stratified by Acute Graft Versus Host Disease GVHD Stage
时间窗: 100 days post transplant
Cumulative incidence of acute GVHD grades II-IV by day 100. Investigators will consider ≥43% incidence of grade II-IV aGVHD not acceptable. Investigators will use 23% incidence rate of GVHD as target. GVHD severity stage and grading and distribution will be measured weekly from day of transplant to day 90 +/- 14 using standard scoring system. Stage of GVHD will be given for each site of involvement (e.g. skin, liver, and gut), as well as a composite score for overall acute GVHD grade. Pathologic confirmation of aGVHD will be dictated by usual clinical practice, and not mandated by this protocol.
次要结局
- Time to Stable Engraftment(100 days post transplant)
- Number of Participants With Primary Disease Relapse(1 year)
- Number of Participants With Non-relapse Mortality(1 year)
- Percentage of Participants With Overall Survival (OS)(1 year)
- Number of Participants Stratified by Chronic Graft Versus Host Disease (GVHD) Stage(100 days post transplant)
- Percentage of Participants With Relapse-free Survival (RFS)(1 year)