Hematopoietic Stem Cell Transplantation for Patients With Severe Sickle Cell Disease Using Myeloablative Conditioning and αβ+ T-cell Depleted Hematopoietic Stem Cells From Partially Matched Familial Donors
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Safety, as Measured by Incidence of Graft Failure, Grade III/IV Irreversible End Organ Toxicity, Grade III/IV aGvHD, or Death Within 100 Days Post-Hap-HSCT
研究概览
简要总结
The purpose of this study is to develop a safe and curative stem cell transplant approach to treating sickle cell disease by assessing the safety of haploidentical hematopoietic stem cell transplantation using αβ+ T-cell depletion for children and adolescents with severe sickle cell disease (SCD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Hemoglobin SS, SC, S-β0 Thalassemia, or SO-Arab Sickle Cell Disease
- •Between the ages of 2 and 25 years (Stage 1: 10-25 years; Stage II: 2-25 years)
- •Lack a fully matched family donor or fully matched unrelated donor register in the National Marrow Donor Program
- •Partially-matched family member with hemoglobin AA (normal) or hemoglobin AS (sickle trait) phenotype
- •SCD with Severe Phenotype, defined by the following criteria: Neurologic manifestations of sickle disease including cerebral vascular accident (CVA), transient ischemic event (TIA) or abnormal MRI findings suggestive of silent infarct; Two or more episodes of acute chest syndrome (ACS) requiring admission for transfusional or respiratory support including supplemental oxygen within [two years] of enrollment in study despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of ACS will also be eligible; History of severe vaso-occlusive (VOC) disease requiring hospitalization and intravenous narcotics on 3 or more occasions per year over the two years prior to enrollment despite hydroxyurea therapy. Patients who cannot tolerate hydroxyurea and who experience multiple episodes of VOC will also be eligible; Other severe phenotype as evidenced by end organ dysfunction related to sickle cell disease.
排除标准
- •Karnofsky or Lansky score < 60%
- •Acute hepatitis or evidence of moderate or severe portal fibrosis on biopsy. (Biopsy will be obtained if patient has been on chronic transfusion therapy > 6 months or has a ferritin > 1000 ng/ml) or AST or ALT >5 times the upper limit of normal
- •Severe renal impairment (as evidenced by creatinine clearance of <50ml/minute glomerular filtration rate (GFR) < 50% predicted normal)
- •Cardiac function that demonstrates shortening fraction less than 26% by cardiac echocardiogram or pulmonary hypertension.
- •Pregnant Female.
- •Lactating female.
- •Pulmonary function with baseline O2 saturation <85% or Diffusing Capacity for Carbon Monoxide (DLCO) on pulmonary function testing (PFT) with a DLCO <40%.
研究组 & 干预措施
Stage I
Stage I will include eligible subjects between the ages of 10-25 years.
干预措施: αβ+ T-cell depletion with Miltenyi CliniMACS system (Device)
Stage II
Stage II will include eligible subjects between the ages of 2-25 years.
干预措施: αβ+ T-cell depletion with Miltenyi CliniMACS system (Device)
结局指标
主要结局
Safety, as Measured by Incidence of Graft Failure, Grade III/IV Irreversible End Organ Toxicity, Grade III/IV aGvHD, or Death Within 100 Days Post-Hap-HSCT
时间窗: 100 days post-Hap-HSCT
Graft Function: efficacy is defined as stable donor engraftment (\>5% total nucleated cell DNA) and donor erythropoiesis that corrects the SCD hematologic phenotype (\<50% HbS in the peripheral blood). Organ Toxicity: grade III/IV irreversible end organ toxicity based on NCI grading Graft Versus Host disease: grade III/IV aGvHD or death within 100 days post- Hap-HSCT
次要结局
- Estimate 1-year Overall and Event-free Survival After Hap-HSCT(1 year post transplant)
- Observe the Incidence of Grades I Through IV Acute GvHD(100 days post transplant)
- Observe Incidence of Severe Acute GvHD as Defined by Grades III Through IV(100 days post transplant)
- Observe the Incidence of Grades I Through IV Chronic GvHD(1 year post transplant)
- Observe Incidence of Severe Chronic GvHD as Defined by Grades III and IV(1 year post transplant)