Reduced Intensity Conditioning With Thiotepa Combined With Busulfan, Fludarabine and Cytarabine in Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Relapsed or Refractory Peripheral T-cell Lymphoma.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- 1y and 2y-progression-free survival (PFS)
研究概览
简要总结
This study is a single-center, single-arm, prospective phase II clinical trial that evaluates the efficacy and safety of an reduced-intensity conditioning (RIC) regimen with thiotepa combined with busulfan, fludarabine, and cytarabine for allogeneic hematopoietic stem cell transplantation in the treatment of relapse and refratory peripheral T-cells lymphoma. The conditioning regimen includes thiotepa at a dose of 5mg/kg/d at d -7 (1 day), fludarabine at 30mg/m2/d from d -6 to d -2 (5 days), cytarabine at 1g/m2/d from d -6 to d -2 (5 days), and busulfan at 3.2mg/kg/d from d -4 to d -3 (2 days). Conditioning begins on day -7, and donor hematopoietic stem cell infusion is performed on day 0. All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year after transplantation. FDG-PET/CT imaging will be adopted every 6 months after transplantation. If disease relapse is suspected during the follow-up period, bone marrow and relapse site examinations will be conducted at any time. The primary study endpoints are the 1-year and 2-year progression-free survival (PFS) rates post-transplant. Secondary study endpoints include the incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant, cumulative relapse rates at 1 year and 2 years post-transplant, 1-year and 2-year overall survival (OS), graft-versus-host disease-free, relapse-free survival (GRFS), non-relapse mortality (NRM), cumulative incidence of chronic GVHD, and the incidence of Cytomegalovirus （CMV）and Epstein-Barr virus（EBV）reactivation within 1 year.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and less than 70 years, regardless of gender
- •Peripheral T-cell lymphoma (PTCL) was diagnosed according to the 2016 WHO criteria and met any of the following criteria: Relapse: Except ALK+ anaplastic large cell lymphoma （ALCL), CR was achieved by standard chemotherapy but disease progressed，and relapse after hematopoietic stem cell transplantation;Refractory: Except ALK+ anaplastic large cell lymphoma （ALCL), the tumor shrank < 50% or progressive disease after 4 courses of standard chemotherapy, or not achieve CR after 6 courses of standard chemotherapy;Not suitable for or refusing autologous hematopoietic stem cell transplantation.
- •Patients must have a suitable hematopoietic stem cell donor:Related donors must have at least 5/10 matches for HLA-A, -B, -C, -DQB1, and - DRB1;Unrelated donors must have at least 8/10 matches for HLA-A, -B, -C, -DQB1, and -DRB1
- •Hematopoietic cell transplantation comorbidity index (HCT-CI) score ≤ 2
- •ECOG (Eastern Cooperative Oncology Group) performance status: 0-2
- •Adequate liver, kidney, and cardiopulmonary function, meeting the following requirements:Serum creatinine ≤ 1.5x ULN (the upper limit of normal);Cardiac function: Ejection fraction ≥ 50%;Baseline oxygen saturation > 92%;Total bilirubin ≤ 2.0 x ULN; ALT and AST ≤ 2.0 x ULN，AKP ≤ 2.0 x ULN;Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40% and FEV1 (Forced Expiratory Volume in 1 second) ≥ 50%
- •Patients must have the ability to understand and be willing to participate in this study and sign an informed consent form
排除标准
- •PTCL patients did not meet the criteria of relapse / refractory.
- •Refuse to adopt allegeneic hematopoietic stem cell transplantation.
- •History of malignancies other than lymphoid tumors within the 5 years prior to screening, except for adequately treated in situ cervical cancer, basal cell carcinoma, squamous cell carcinoma of the skin, and curatively treated localized prostate cancer or ductal carcinoma in situ
- •HCT-CI score ≥
- •Any unstable systemic diseases, including but not limited to unstable angina, recent cerebrovascular accidents or transient ischemic attacks within the 3 months prior to screening, myocardial infarction within the 3 months prior to screening, congestive heart failure (New York Heart Association [NYHA] class ≥ III), severe arrhythmias requiring drug treatment after pacemaker implantation, significant liver, kidney, or metabolic diseases, and pulmonary arterial hypertension.
- •Active, uncontrolled infections, including those associated with hemodynamic instability, new or worsening infection symptoms or signs, new infectious lesions on imaging, or persistent unexplained fever without signs or symptoms of infection.
- •HIV-infected individuals.
- •Active hepatitis B (HBV) or active hepatitis C (HCV) requiring antiviral therapy.
- •History of autoimmune diseases
- •Pregnant or breastfeeding women.
- •Fertile males and females unwilling to use contraception during the treatment period and for 12 months after treatment.
研究组 & 干预措施
intervention arm
Participants will receive allogenetic hematopoietic stem cell transplantation (allo-HSCT) with the reduced intensity conditioning regimen including thiotepa(5mg / kg / d-7d ( 1d )), fludarabine (30mg / m2 / d, -6d--2d ( 5d )), Ara-C (1g / m2 / d, -6d--2d ( 5d )), and busulfan(3.2mg / kg / d, -4d-3d ( 2d )).
干预措施: Thiotepa (Drug)
结局指标
主要结局
1y and 2y-progression-free survival (PFS)
时间窗: up to 1 years for the 1y-PFS and up to 2 years for the 2y-PFS
1-year and 2-year progression-free survival (PFS) rates post-transplant
次要结局
- 1y and 2y-overall survival (OS)(up to 1 years for the 1y-OS and up to 2 years for the 2y-OS)
- acute graft-versus-host disease (aGVHD)(up to 180 days)
- 1y and 2y-cumulative relapse rates (CIR)(up to 1 years for the 1y-CIR and up to 2 years for the 2y-CIR)
- cumulative incidence of chronic GVHD(up to 2 years)
- CMV and EBV reactivation(up to 1 year)
- non-relapse mortality (NRM)(up to 2 years)
- graft-versus-host disease-free, relapse-free survival (GRFS)(up to 2 years)
研究者
Xianmin Song, MD
Professor
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine