Reduced Intensity Matched Sibling Bone Marrow Transplantation for Sickle Cell Anemia in Patients 2-30 Years Old
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Number of Participants With Graft Failure
研究概览
简要总结
This protocol will be investigating the use of stem cell transplantation, in related donors, to cure sickle cell disease. Sickle cell disease is a recessive disorder caused by a point mutation that results in the substitution of valine for glutamic acid at the sixth position in the B-chain of hemoglobin. This leads to sickling of the red blood cells under many conditions, such as hypoxia, dehydration, and hyperthermia. The sickling leads to vaso-occlusion, which causes irreversible damage in almost all systems in the body, including the central nervous system (CNS), lungs, heart, bones, eyes, liver, and kidneys.
详细描述
Primary objective:
- To determine disease free survival (DFS) at two years after matched sibling transplant using bone marrow (BM) after a conditioning regimen consisting of distal timed Alemtuzumab, Fludarabine, and Melphalan for patients 2-30 y/o
Secondary objectives:
- Overall survival
- Rate of neutrophil and platelet engraftment for BM
- Incidence of graft failure
- Incidence of grade II-IV and grade III-IV acute graft vs host disease (GVHD)
- Incidence of chronic GVHD
- Incidence of other transplant complications, such as veno-occlusive disease, central nervous system (CNS) toxicity, and idiopathic pneumonia syndrome (IPS)
- Incidence of reactivation of CMV, EBV, adenovirus, BK/JC virus
- Incidence of invasive fungal disease
- Time to immune reconstitution via monitoring of lymphocyte subpopulations and immunoglobulin levels
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
- 2 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient Eligibility
- •Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single or double) with a total TNC dose of greater than 5 x 107/kg recipient weight)
- •Hb SS, S-thal0, S-thal+, SC
- •Evidence of ongoing hemolysis: Hb<10, retic >5%, LDH > 500, TB>2
- •Karnofsky/Lansky score >50
- •LVSF>26% or LVEF>40%
- •DLCO >40% or O2 sat >85% for those patients that can't perform PFTs
- •GFR >70 and serum creatinine < 1.5 * ULN for age
- •ALT and AST < 5 x ULN, direct bilirubin <2 x ULN
- •If the patient has been on chronic transfusion or has a ferritin >1000, liver biopsy should be done and show no evidence of bridging fibrosis or cirrhosis
- •Exclusion criteria
- •Evidence of uncontrolled bacterial, viral, or fungal infection within one month prior to initiation of the conditioning regimen
- •Pregnant or breastfeeding
- •HIV positive
- •Written informed consent not obtained
排除标准
- 未提供
研究组 & 干预措施
Related donor
Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan.
- Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below.
Day Treatment
- -22 Alemtuzumab 3mg IV (test dose)
- -21 Alemtuzumab 10mg IV
- -20 Alemtuzumab 15mg IV
- -19 Alemtuzumab 20mg IV
- -8 Fludarabine 30mg/m2 IV
- -7 Fludarabine 30mg/m2 IV
- -6 Fludarabine 30mg/m2 IV
- -5 Fludarabine 30mg/m2 IV
- -4 Fludarabine 30mg/m2 IV
- -3 Melphalan 140mg/m2 IV
- -2 Rest Day
- -1 Rest Day
- 0 Stem Cell Infusion
干预措施: Alemtuzumab (Drug)
Related donor
Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan.
- Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below.
Day Treatment
- -22 Alemtuzumab 3mg IV (test dose)
- -21 Alemtuzumab 10mg IV
- -20 Alemtuzumab 15mg IV
- -19 Alemtuzumab 20mg IV
- -8 Fludarabine 30mg/m2 IV
- -7 Fludarabine 30mg/m2 IV
- -6 Fludarabine 30mg/m2 IV
- -5 Fludarabine 30mg/m2 IV
- -4 Fludarabine 30mg/m2 IV
- -3 Melphalan 140mg/m2 IV
- -2 Rest Day
- -1 Rest Day
- 0 Stem Cell Infusion
干预措施: Fludarabine (Drug)
Related donor
Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan.
- Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below.
Day Treatment
- -22 Alemtuzumab 3mg IV (test dose)
- -21 Alemtuzumab 10mg IV
- -20 Alemtuzumab 15mg IV
- -19 Alemtuzumab 20mg IV
- -8 Fludarabine 30mg/m2 IV
- -7 Fludarabine 30mg/m2 IV
- -6 Fludarabine 30mg/m2 IV
- -5 Fludarabine 30mg/m2 IV
- -4 Fludarabine 30mg/m2 IV
- -3 Melphalan 140mg/m2 IV
- -2 Rest Day
- -1 Rest Day
- 0 Stem Cell Infusion
干预措施: Melphalan (Drug)
Related donor
Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan.
- Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below.
Day Treatment
- -22 Alemtuzumab 3mg IV (test dose)
- -21 Alemtuzumab 10mg IV
- -20 Alemtuzumab 15mg IV
- -19 Alemtuzumab 20mg IV
- -8 Fludarabine 30mg/m2 IV
- -7 Fludarabine 30mg/m2 IV
- -6 Fludarabine 30mg/m2 IV
- -5 Fludarabine 30mg/m2 IV
- -4 Fludarabine 30mg/m2 IV
- -3 Melphalan 140mg/m2 IV
- -2 Rest Day
- -1 Rest Day
- 0 Stem Cell Infusion
干预措施: Stem Cells (Procedure)
结局指标
主要结局
Number of Participants With Graft Failure
时间窗: 2 years
Primary endpoint: In each group, the Number of participants with Graft Failure at the 2 years endpoint will be estimated using the Kaplan Meier product limit estimator.
次要结局
- Overall Survival(2 years)