A Phase III Randomized, Multicenter Trial Comparing Sirolimus/Tacrolimus With Tacrolimus/Methotrexate as Graft-versus-Host Disease (GVHD) Prophylaxis After HLA-Matched, Related Peripheral Blood Stem Cell Transplantation (BMT CTN #0402)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 304
- 试验地点
- 24
- 主要终点
- Rate of Grades II-IV Acute GVHD-free Survival
研究概览
简要总结
The study is designed as a phase III, randomized, open label, multicenter, prospective, comparative trial of sirolimus and tacrolimus versus tacrolimus and methotrexate as graft-versus-host disease (GVHD) prophylaxis after human leukocyte antigen (HLA)-matched, related, peripheral blood stem cell transplantation in individuals with hematologic cancer. Participants will be stratified by transplant center and will be randomly assigned to the sirolimus/tacrolimus or tacrolimus/methotrexate arms at a 1:1 ratio.
详细描述
BACKGROUND:
Stem cell transplantation is a standard therapy for acute and chronic leukemias and myelodysplastic disorders. A common problem that may occur after a stem cell transplant is a condition known as GVHD. The purpose of this study is to compare two combinations of medications to see which is better at preventing GVHD. The combinations of medications in this study are:
- Sirolimus and tacrolimus
- Methotrexate and tacrolimus
Doctors want to know if one combination is better than the other or if they both have the same result.
DESIGN NARRATIVE:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •6/6 HLA-matched sibling, defined by Class I (HLA-A and B) serologic typing (or higher resolution) and Class II (HLA-DRBI) molecular typing, who is willing to donate peripheral blood stem cells, and meets institutional criteria for stem cell donation. The donor must be medically eligible to donate stem cells, according to individual transplant center criteria. Pediatric patients for whom a pediatric sibling donor is not anticipated to be a suitable leukapheresis candidate are not eligible.
- •Karnofsky performance status of at least 70% or Lansky performance status of at least 70% for participants less than 16 years old
- •For participants less than 18 years old, willing and able to take oral medications, per the treating physician's recommendations
排除标准
- •Prior allogeneic or autologous transplant using any hematopoietic stem cell source
- •Seropositive for the human immunodeficiency virus (HIV)
- •Uncontrolled bacterial, viral, or fungal infection (currently taking medication and progression of clinical symptoms)
- •Pregnant (positive serum human chorionic gonadotropin [β-HCG] test) or breastfeeding within 4 weeks of study entry
- •Kidney function: serum creatinine outside the normal range for age, or measured creatinine clearance less than 50 mL/min/1.72m^2 within 4 weeks of study entry
- •Liver function: most recent direct bilirubin, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) greater than two times the upper limit of normal within 4 weeks of study entry
- •Lung disease: in adults, forced vital capacity (FVC) or forced expiratory volume in one second (FEV1) less than 60% of predicted value (corrected for hemoglobin); in children, overt hypoxemia, as measured by an oxygen saturation of less than 92% within 4 weeks of study entry
- •Cardiac ejection fraction of less than 45% in adults and children, or less than 26% shortening fraction in children within 4 weeks of study entry
- •Cholesterol level greater than 500 mg/dL or triglyceride level greater than 500 mg/dL while being treated, or not on appropriate lipid-lowering therapy within 4 weeks of study entry
- •Prior history of allergy to sirolimus
- •Requires voriconazole at time of study entry
- •Currently receiving another investigational drug unless cleared by the protocol officer or protocol chair
- •Participants with a history of cancer, other than resected basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent for more than 5 years previously will be allowed. Cancer treated with curative intent for less than 5 years previously will not be allowed unless approved by the protocol officer or protocol chair.
研究组 & 干预措施
Tacrolimus/Methotrexate
Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
干预措施: Tacrolimus (Drug)
Tacrolimus/Methotrexate
Patients will be given Tacrolimus and Methotrexate for GVHD prophylaxis.
干预措施: Methotrexate (Drug)
Tacrolimus/Sirolimus
Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.
干预措施: Tacrolimus (Drug)
Tacrolimus/Sirolimus
Patients will be given Tacrolimus and Sirolimus for GVHD prophylaxis.
干预措施: Sirolimus (Drug)
结局指标
主要结局
Rate of Grades II-IV Acute GVHD-free Survival
时间窗: Day 114
The primary objective is to compare rates of 114-day Grades II-IV acute GVHD-free survival post randomization for HLA-matched, related donor allogeneic peripheral blood stem cell transplantation using two different GVHD prophylaxis regimens. Participants are graded on a scale of 1 to 4 according to their symptoms and organs involved, where 4 represents a worse grade.
次要结局
- Incidence of Acute GVHD(Measured at Day 100)
- Time to Neutrophil and Platelet Engraftment(Measured through Day 100)
- Mucositis Severity(Measured at Day 21)
- Rate of Veno-occlusive Disease (VOD)(Measured through Day 100)
- Thrombotic Microangiopathy (TMA) Infection(Measured through Day 100)
- Reactivation of Cytomegalovirus (CMV) Infection(Measured at Year 2)
- Treatment-related Mortality(Measured at Day 100 and Year 2)
- Malignant Disease Relapse(Measured at Year 2)
- Overall Survival(Measured at Year 2)
- Infections(Measured at Year 2)
- Time to Discharge After Transplant(Measured at Year 2)