A Study Evaluating BPX-501 T Cells and AP1903 for Prevention of Graft Versus Host Disease (GVHD) After Haploidentical, Related, T Cell-Depleted Hematopoietic Cell Transplantation for Non-Malignant Diseases
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Adverse Events
研究概览
简要总结
The purpose of this study is to determine a safe dose of BPX-501 gene modified T cells infused after a haplo-identical stem cell transplant to facilitate engraftment and the safety of Rimiducid (AP1903) on day 7 to prevent GVHD.
详细描述
This is a single arm dose finding study evaluating the safety and efficacy of a BPX 501 infusion (T cells genetically modified with the inducible Caspase 9 suicide gene) of 3x10E6 to 1X10E7 cells/kg followed by a Rimiducid infusion on day 7 after a partially mismatched, related, T cell-depleted hematopoietic cell transplantation (HCT) in patients with non-malignant diseases. The purpose of this clinical trial is to determine the dose of BPX 501 T cell infusion with subsequent planned infusion of Rimiducid which can facilitate engraftment and prevent the occurrence of GVHD.
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
- 4 Months 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must meet eligibility criteria for allogeneic transplantation
- •Lack of suitable conventional donor (10/10 allele matched related or unrelated donor) or presence of rapidly progressive disease not permitting time to identify an unrelated donor
- •Males or females
- •Age < 55 years old and > 4 months
- •Diagnosis of a nonmalignant disorder considered treatable by HCT.
- •HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, DRBl, and DQB1 loci.
- •i. A minimum match of 5/10 is required. ii. The donor and recipient must be identical, as determined by high resolution typing, in at least one allele of each of the following
- •If capable of reproduction, patient must agree to use contraception or abstinence to prevent pregnancy during the first year of enrollment and treatment.
- •Informed consent signed by patient (if ≥18 years old) or parent/guardian (if <18 years old).
- •Fanconi anemia patients ONLY i) Patients must meet one of the following criteria to be eligible for this study:
- •Any patient with Fanconi anemia and bone marrow failure involving 2 of the following 3 lineages: granulocyte count <0.5 x 109/L, platelet count <20 x 109/L, or hemoglobin <8 g/dL.
- •Any patient with Fanconi anemia who requires red blood cell or platelet transfusions because of marrow failure
- •Any patient with Fanconi anemia who has a life-threatening bone marrow failure involving a single hematopoietic lineage.
排除标准
- •Serious organ dysfunction
- •Pregnant or breast-feeding
- •Evidence of HIV infection
- •Bovine product allergy
- •Patients with an active infectious disease
- •Patients with Fanconi anemia with AML/MDS.
结局指标
主要结局
Adverse Events
时间窗: 24 months
To determine the safety (as defined by non-responsive Grade III-IV GVHD to rimiducid) of HCT with HLA-haploidentical CD34+ selected peripheral blood stem cell (PBSC) grafts and BPX 501 T cells followed by scheduled rimiducid infusion on Day 7. this outcome measure is reported as number of patients who experienced the AE of Grade III-IV GVHD that was not non-responsive to rimiducid (safety switch) administration.
Engraftment
时间窗: Day 28
Determine the engraftment rate (defined as \>50% donor CD3 chimerism) on day 28 after HCT with HLA-haploidentical CD34+ selected PBSC grafts per dose cohort of BPX 501 T cells followed by Rimiducid infusion on Day 7. NOTE: only one patient was enrolled who received the dose of 5x 10\^6cell/kg dose of BPX-501
次要结局
- GvHD(Month 24)
- Immune Reconstitution(Month 24)
- Graft Rejection(Month 24)
- Infection Rates(Day 200)
- Rimiducid Activity(Month 24)
- High Grade Toxicity(Month 24)