Closely Matched Unrelated Donor Peripheral Blood Stem Cell Transplantation With TCRαβ+ T Cell and B Cell Depletion For Patients With Sickle Cell Disease and Thalassemia Major
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Time to neutrophil engraftment
研究概览
简要总结
This is a single arm pilot study of peripheral stem cell transplantation (PSCT) with ex vivo t-cell receptor alpha beta+(TCRαβ+) T cell and cluster of differentiation 19+ beta (CD19+ B) cell depletion of unrelated donor (URD) grafts using the CliniMACS device in patients with sickle cell disease (SCD) and beta thalassemia major (BTM).
详细描述
This is a single arm pilot study of peripheral stem cell transplantation (PSCT) with ex vivo TCRαβ+ T cell and CD19+ B cell depletion of URD grafts using the CliniMACS device in patients with SCD and BTM. Apart from CliniMACS-based cell processing, PSCT will be performed according to current standards of care in the Children's Hospital of Philadelphia (CHOP) Cell Therapy and Transplant Section, including the use of a standard chemotherapy conditioning regimen and standard follow-up laboratory assessments. The study will determine efficacy of this strategy in terms of engraftment, rates of acute and chronic Graft versus Host Disease (GvHD), and one-year overall and event-free survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Severe Sickle Cell Disease
- •Genotype: Hemoglobin SS, Hemoglobin SC, Hemoglobin SD, SOArab, or Hemoglobin SBeta thalassemia
- •Must have at least one of the following disease manifestations
- •Clinically symptomatic neurologic event (stroke) or any neurologic deficit lasting greater than 24 hours at any time prior to enrollment
- •History of two or more episodes of vaso-occlusive events (VOE) per year in the 2 years preceding enrolment. Patients must be refractory to hydroxyurea, defined as developing VOE despite receiving hydroxyurea for at least 6 months. Patients who are intolerant of hydroxyurea may also be enrolled.
- •Vaso-occlusive events include:
- •Acute chest syndrome
- •Pain episodes requiring intravenous pain management and/or hospitalization
- •Splenic sequestration (defined as a 2 g/dL drop in hemoglobin in the setting of an acutely enlarging spleen. This will be determined as part of clinical care and prior to the research)
- •Administration of regular red blood cell (RBC) transfusion therapy, defined as receiving ≥ 8 RBC transfusions in the year preceding enrollment to prevent sickle cell-related complications of any kind per treating hematologist's judgment.
- •Beta Thalassemia Major
- •Genotype: Confirmed Beta Thalassemia genotype by molecular genetic testing (May include E/Beta0 and Beta0/Beta+ genotypes)
- •Must meet clinical diagnosis of transfusion-dependent thalassemia, defined as need for ≥ 8 RBC transfusions per year in the two years preceding study enrollment.
排除标准
- •Patients who do not meet disease, organ or infectious criteria.
- •Previous Hematopoietic stem cell transplant (HSCT)
- •Patients with no suitable unrelated donor available. Patients with suitable fully matched related donor are also not eligible.
- •Pregnant females. All females of childbearing potential must have negative pregnancy test.
- •Participation in a clinical trial in which the patient receives an investigational drug must be discontinued prior to the time of initiation of transplant therapy. Specifically transplant chemotherapy should not begin until at least 3 half-lives after last use of the investigational drug.
- •Severe RBC alloimmunization, defined as inability to receive packed RBC transfusion therapy due to anti-RBC antibodies. Patients with high titer anti-donor human leukocyte antigen (HLA) antibodies detected on screening may be enrolled if they are willing to undergo HLA antibody desensitization therapy.
研究组 & 干预措施
Sickle Cell Disease
Patients with Sickle Cell Disease (SCD) will be given previously established, disease-specific chemotherapy based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from closely matched unrelated donors.
干预措施: CliniMACS (Device)
Beta Thalassemias Major
Patients with Beta Thalassemias Major (BTM) will be given previously established, disease-specific chemotherapy based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from closely matched unrelated donors.
干预措施: CliniMACS (Device)
结局指标
主要结局
Time to neutrophil engraftment
时间窗: Up to 60 days post-transplantation
Number of days to neutrophil engraftment (first day of ANC \>500/µl for the first of 3 consecutive days)
Incidence of chronic graft vs. host disease (GVHD)
时间窗: Up to three years post-transplantation
Number of patients with Grade II-IV acute GVHD, Severe Grade III-IV acute GVHD, and Chronic Extensive GVHD
Rate of graft failure
时间窗: Up to 1year post-transplantation
Number of patients with primary graft failure (defined as no evidence of neutrophil engraftment by day +30 after stem cell infusion) and secondary graft failure (defined as ANC \<500 for at least 7-10 days after initial engraftment occurs in the absence of known infection or drug-mediated suppression, and confirmed by hypocellular bone marrow biopsy and/or total donor chimerism percentage from blood or bone marrow \< 10 percent)
Incidence of acute graft vs. host disease (GVHD)
时间窗: Up to 100 days post-transplantation
Number of patients with acute GvHD (graded according to the current guidelines for reporting by the Center for International Bone Marrow Transplant Registry)
Rate of Graft Failure
时间窗: Up to 1 year post-transplantation
Number of patients with primary graft failure (defined as no evidence of neutrophil engraftment by day +30 after stem cell infusion) and secondary graft failure (defined as ANC \<500 for at least 7-10 days after initial engraftment occurs in the absence of known infection or drug-mediated suppression, and confirmed by hypocellular bone marrow biopsy and/or total donor chimerism percentage from blood or bone marrow \< 10 percent)
Time to Neutrophil Engraftment
时间窗: Up to 60 days post-transplantation
Number of days to neutrophil engraftment (first day of ANC \>500/µl for the first of 3 consecutive days)
Incidence of Acute Graft vs. Host Disease (GVHD)
时间窗: Up to 100 days post-transplantation
Acute GvHD was assessed by the number of patients who developed acute graft-versus-host disease, graded according to current Center for International Bone Marrow Transplant Registry (CIBMTR) reporting guidelines. Grading follows established criteria based on the severity of skin, liver, and gastrointestinal involvement, including extent of rash, bilirubin elevation, and gastrointestinal symptoms (e.g., diarrhea volume). Evaluation was performed by clinical assessment and laboratory data consistent with standard transplant-related acute GvHD grading practices.
Incidence of Chronic Graft vs. Host Disease (GVHD)
时间窗: Up to two years post-transplantation
Number of patients with Grade II-IV acute GVHD, Severe Grade III-IV acute GVHD, and Chronic Extensive GVHD
次要结局
- Probability of overall survival (OS)(1 year post-transplantation)
- Number of deaths due to treatment(Up to 100 days post-transplantation)
- Probability of event-free survival (EFS)(Up to 1 year post-transplantation)
- Incidence of viral reactivation and symptomatic viral infection(Up to 1 year post-transplantation)
- Number of Deaths Due to Treatment(Up to 100 days post-transplantation)
- Probability of Event-free Survival (EFS)(Up to 1 year post-transplantation)
- Probability of Overall Survival (OS)(1 year post-transplantation)
- Incidence of Viral Reactivation and Symptomatic Viral Infection(Up to 1 year post-transplantation)
研究者
Timothy Olson
Attending Physician
Children's Hospital of Philadelphia