Sitagliptin Efficacy and Safety for Prevention of Acute Graft Versus Host Disease in Patients Receiving Alternative Donor Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 190
- 试验地点
- 1
- 主要终点
- Development Grade II-IV Acute GVHD by Day +100 Following Transplantation
研究概览
简要总结
Primary Objective:
It is hypothesized that the efficacy of Sitagliptin would reduce the incidence of grade II-IV acute Graft Versus Host Disease (GVHD) by day +100 post-transplant in patients undergoing alternative donor (related haploid or unrelated donor ) allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and receiving standard GVHD prophylaxis.
Secondary Objectives
The following descriptive secondary objectives will be studied:
- Determine the tolerability and potential toxicity of sitagliptin in patients undergoing allogeneic HSCT.
- Determine the cumulative incidence of grades II-IV acute GVHD by day +100.
- To investigate the cumulative incidence of grades III-IV acute GVHD.
- To investigate the engraftment kinetics of absolute neutrophil count and platelets.
- To evaluate the incidence of Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and other infections occurring during the 100 days post-transplant.
- To study non-relapse mortality (NRM) at day +100, and 1 year post-transplant.
- Determine the overall survival at 1 year post-transplant.
- Determine the incidence of chronic GVHD.
- Determine the cumulative incidence of relapse of the primary hematological malignancy.
详细描述
This is a Prospective, Multi-center, Open-label, Randomized, Controlled clinical trial of Sitagliptin for the prevention and safety of aGVHD after Alternative Donor hematopoietic stem cell transplantation.
190 adult patients with hematologic malignancies receiving haploid or unrelated donor sourced HSCT are planned to be enrolled competitively in this study from 5 clinical centers in China. These patients will be randomly assigned to two groups of 95 patients each, which one is experimental group and the other is control group. 95 patients in experimental group will receive Sitagliptin combined with Standard prophylaxis for GVHD. 95 patients in the control group will receive Standard prophylaxis regimen for GVHD of Alternative Donor HSCT.
Control group uses antithymocyte immunoglobulin (ATG)+cyclosporin A (CSA)+MMF+MTX for GVHD prophylaxis with the details as follows: CSA 3mg/kg continuous i.v. drip, start before Day -7, change to p.o. when gastrointestinal function recovers with a dose of 5mg/kg as two divided doses, maintaining CSA within 150-250ng/ml（If CsA cannot be tolerated, tacrolimus may be used as an alternative.）; MTX 15mg/m2,Day +1, 10mg/m2,Days +3, +6, and +11; MMF 0.5g bid, starting from Day -7 to day +30 for one month; ATG 2.5mg/kg/d, Day -4 to Day -1.
Experimental group will take Sitagliptin orally from d-1 to d+14 in addition to Standard Prophylaxis Regimen.
With regard to the content of dose reduction of CSA (including time and reduction rate), it is recommended for patients with hematologic malignancies in standard risk group to start to reduce dose after 3-6 months in the absence of GVHD and reoccurrence. The specific reduction rate can be determined at each site; the patients with GVHD will be managed by routine practice in this site.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient age ≥ 18 to ≤ 60 years
- •Eastern Cooperative Oncology Group (ECOG）score 0-2 points / Karnofsky score ≧80
- •To receive allogeneic hematopoietic stem cell transplantation from related haploid or unrelated donor
- •The pretreatment of modified Bu/Cy+ATG scheme was planned.
- •Patients with malignant hematological diseases indicated by transplantation and in complete remission (CR) state.
- •Expected survival ≥ 3 months
- •Signed written informed consent (Patient must be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent)
- •Agree to use effective contraception
排除标准
- •Prior allogeneic hematopoietic stem cell transplant
- •Allergy/intolerance to Sitagliptin
- •There are contraindications for Sitagliptin use.
- •Moderate or severe renal insufficiency
- •Patients with diabetes mellitus requiring insulin secretagogues and/or insulin
- •Human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection
- •Active infection that is difficult to control
- •Vital organ function cannot tolerate transplantation
- •Other malignant tumors outside the blood system, except the following diseases: malignant tumors that have been cured for 3 years without active lesions; Adequate treatment of non-melanoma skin cancer without active foci of malignant amygdala and carcinoma in situ
- •There is evidence that may interfere with the study or make patients at risk of serious complications or medical conditions, including but not limited to serious cardiovascular diseases (such as New York heart association class III or IV heart disease over the past six months of myocardial infarction, unstable type of cardiac arrhythmias) or unstable angina and/or severe lung disease (e.g. History of severe obstructive pulmonary disease and symptomatic bronchospasm)
- •Pregnant or lactating women
- •Any life-threatening medical condition or organ system dysfunction considered by the investigator may endanger the patient's safety by interfering with the absorption or metabolism of sitagliptin or putting study results at unnecessary risk
研究组 & 干预措施
Sitagliptin Group
95 adult patients with hematologic malignancies receiving Alternative Donor HSCT, who will receive Sitagliptin combined with Standard prophylaxis regimen for GVHD of Alternative Donor HSCT.
干预措施: Sitagliptin + Standard Prophylaxis (Drug)
Standard Group
95 adult patients with hematologic malignancies receiving Alternative Donor HSCT, who will only receive Standard prophylaxis regimen for GVHD of Alternative Donor HSCT
干预措施: Standard Prophylaxis (Drug)
结局指标
主要结局
Development Grade II-IV Acute GVHD by Day +100 Following Transplantation
时间窗: up to 100 days
Percent of patients and the 95% Confidence interval who have Grade II-IV Acute GVHD by 100 days following transplantation. Only patients who were on the study for at least 100 days post transplantation were included in the analysis.
次要结局
- Percentage of Patients With Relapse of the Primary Hematological Malignancy at 1 Year(1 year from transplant)
- Development Grade II-IV Acute GVHD at Day +100(100 days from transplant)
- Cumulative incidence of early transplant-related death (TRM) within 100 days after transplantation(100 days from transplant)
- Median Time to Engraftment of Platelets(up to 4 months)
- Percentage of Patients With Grade III-IV Acute GVHD at Day +100(100 days from transplant)
- Median Time to Engraftment of Neutrophils(up to 1 month)
- Number of Unique Patients With Infections by Day +100(100 days from transplant)
- Percentage of Patients With Non-relapse Mortality (NRM) at +1 Year(1 year from transplant)
- Percentage of Patients Surviving at +1 Year(1 year from transplant)
- Percentage of Patients Diagnosed With Chronic GVHD at 1 Year(1 year from transplant)