A Phase II Pilot Study of Nonmyeloablative Conditioning Hematopoietic Stem Cell Transplantation in Children With Sickle Cell Disease Who Have a Matched Related Major ABO-Incompatible Donor (Sickle-AID)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Incidence of pure red cell aplasia (PRCA)
研究概览
简要总结
The aim of this study to evaluate the safety and efficacy of a nonmyeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with sickle cell disease (SCD) who have a matched related major ABO-incompatible donor. The nonmyeloablative regimen will use alemtuzumab, total body irradiation (TBI) and sirolimus for immune suppression. This study will expand the access of HSCT for patients with SCD who are currently not eligible because of donor restrictions.
详细描述
Sickle cell disease (SCD) is a debilitating chronic blood disorder with multi-system end-organ damage that leads to morbidity and early mortality. The only cure for SCD is hematopoietic stem cell transplantation (HSCT), which given the risks with unrelated HSCT, is only an option for a minority of patients who have a matched sibling donor.
In the field of HSCT, blood group ABO incompatibility between donor and recipient is not a contraindication and several studies do not show compromised outcomes. However, in the context of nonmyeloablative (NMA) conditioning and major ABO-incompatibility, when the recipient has existing antibodies to donor red blood cells, pure red cell aplasia (PRCA) may occur.
This phase II pilot study will enroll SCD patients with a matched related major ABO-incompatible donor to determine the safety and efficacy of NMA-HSCT. Biological studies will include a plan to study and monitor red cell engraftment in this population to facilitate early detection and interventional measures to prevent and treat PRCA.
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
- 1 Year 至 19 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be ≥ 12 months and < 19 years of age at the time of study enrollment.
- •Patients must have sickle cell disease as defined by hemoglobin electropheresis, as follows:
- •homozygous Hb S disease (HbSS),
- •sickle-Hb C disease (HbSC),
- •sickle beta-plus-thalassemia (HbS/β+), or
- •sickle beta-null-thalassemia (HbS/βo)
- •Patients must meet standard eligibility criteria to undergo HSCT, including but not limited to one or more of the following:
- •history of repeated (more than 1) bony (vaso-occlusive) crisis
- •history of stroke
- •elevated transcranial Doppler velocity not eligible for hydroxyurea, as per TWiTCH trial (ie. severe vasculopathy)
- •history of acute chest crisis or splenic sequestration crisis
- •history of priapism in males
- •history of osteonecrosis
- •pulmonary hypertension as documented by tricuspid regurgitation jet velocity (TRV) > 2.5 m/s on echocardiogram
- •red cell allo-immunization (≥ 2 antibodies) during long term transfusion therapy
- •Sickle complications should be present despite the use of hydroxyurea, but this is not an absolute requirement, if the treating team considers the patient to be at high risk for further crisis episodes.
排除标准
- •Patients who are unable to comply with or follow the study protocol.
- •Patients with known hypersensitivity to sirolimus, its derivatives or to any of its components.
研究组 & 干预措施
Non-myeloablative conditioning
Non-myeloablative conditioning
干预措施: Total Body Irradiation (Radiation)
Non-myeloablative conditioning
Non-myeloablative conditioning
干预措施: Alemtuzumab (Drug)
Non-myeloablative conditioning
Non-myeloablative conditioning
干预措施: Sirolimus (Drug)
结局指标
主要结局
Incidence of pure red cell aplasia (PRCA)
时间窗: 6 months from enrollment
Clinical definition: reticulocytopenia \< 10x109/L (\< 1%) lasting more than 60 days after HSCT, or Pathological definition: the absence of erythroid precursors in the marrow in the setting of adequate myeloid, lymphoid and megakaryocytic precursors
次要结局
- RBC chimerism measured by peripheral blood flow cytometry(12 months)
- Secondary graft failure(24 months)
- Disease recurrence(24 months)
- RBC chimerism measured by bone marrow BFU-erythroid forming colonies(2 months)
- Primary graft failure(6 weeks)
- Incidence and severity of acute GVHD(100 days)
- Incidence and severity of chronic GVHD(24 months)
研究者
Tony H. Truong
Pediatric Hematologist/Oncologist
University of Calgary