A Pilot Study of Reduced Intensity Conditioning in Pediatric Patients <21 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Determine the Feasibility of Attaining Acceptable Rates of Donor Cell Engraftment (>25% Donor Cells at 180 Days) Following RIC Regimens in Children < 21 Years Receiving UCBT for Non-malignant Disorders.
研究概览
简要总结
The primary objective is to determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for non-malignant disorders.
详细描述
Myeloablative doses of chemotherapy and/or radiation therapy are employed with the primary purpose of eradicating malignant cells. Additionally, these regimens exert varying degree of immunosuppression/immunoablation that aids in reducing the likelihood of rejection by host hematopoietic cells. However, myeloablative /immunoablative regimens have also been associated with significant regimen related toxicity (RRT) and regimen related mortality (RRM) that may cause death in up to 20% of patients and significantly higher rate of severe organ dysfunction or failure. While most of these RRT occur typically in the first 100 days [ e.g. VOD (veno occlusive disease), pulmonary or intracranial hemorrhage, multiorgan failure (MOF)], there are significant long term toxicities of TBI and/or chemotherapy including growth impairment, gonadal dysfunction/failure, hypothyroidism, cataracts, neurocognitive impairment, and second malignancies.
The primary objective is to determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for non-malignant disorders.
The secondary objectives are:
- To describe the pace of neutrophil and platelet recovery
- To evaluate the pace of immune reconstitution.
- To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant
- To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD
- To describe the incidence of grade 3-4 organ toxicity
- To evaluate long-term complications, such as sterility, endocrinopathy, and growth failure
- To evaluate the incidence of late graft failures at 2 years post-transplant
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •0-21 years of age with a diagnosis of a immunodeficiency, congenital marrow failure syndrome, inborn error of metabolism, or hereditary anemia
- •Appropriately matched related or unrelated umbilical cord blood unit with a cell dose ≥ 3 x 10e7cells/kg
- •Performance score (lansky or karnofsky) greater than or equal to 70
- •Adequate organ function (Creatinine ≤ 2.0 mg/dl and creatinine clearance ≥ 50 ml/min/1.73 m2; Hepatic transaminases (ALT/AST) ≤ 4 x normal; Shortening fraction >26% or ejection fraction >40% or > 80% of normal value for age; Pulmonary function tests demonstrating CVC or FEV1/FVC of >60% of predicted for age.)
- •Informed consent
- •Not pregnant or breast feeding
- •Minimum life expectancy of at least 6 months
- •HIV negative
- •No uncontrolled infections at the time of cytoreduction
- •Disease specific inclusion criteria
排除标准
- •Patients with hemoglobinopathies > 3 years of age
- •UCB unit with a total nucleated cell count < 3 x 10e7/kg or > 2 antigen mismatching
- •Available HLA-matched related living donor able to donate without previous UCB donation
- •Allogeneic hematopoietic stem cell transplant within the previous 6 months
- •Any active malignancy, MDS, or any history of malignancy
- •Severe acquired aplastic anemia
- •DLCO < 60% of normal value for age; requirement for supplemental oxygen
- •Uncontrolled bacterial, viral or fungal infection (currently taking medication and progression of clinical symptoms)
- •Pregnancy or nursing mother
- •HIV/HTLV seropositive, Hep B surface antigen positive, or HCV RNA positive by PCR
- •Any condition that precludes serial follow-up
研究组 & 干预措施
RIC Cord Blood Transplant
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant
干预措施: Unrelated Umbilical Cord Blood Transplant (Biological)
RIC Cord Blood Transplant
Reduced Intensity Conditioning for Umbilical Cord Blood Transplant
干预措施: Reduced Intensity Conditioning (Drug)
结局指标
主要结局
Determine the Feasibility of Attaining Acceptable Rates of Donor Cell Engraftment (>25% Donor Cells at 180 Days) Following RIC Regimens in Children < 21 Years Receiving UCBT for Non-malignant Disorders.
时间窗: 180 days post transplant
Determine the feasibility of attaining acceptable rates of donor cell engraftment (\>25% donor cells at 180 days) following reduced intensity conditioning regimens in children \< 21 years receiving cord blood transplant for non-malignant disorders.
次要结局
- To Describe the Pace of Neutrophil Recovery(42 days post transplant)
- To Evaluate the Pace of Immune Reconstitution.(1 year post transplant)
- To Determine the Overall Survival at day180 Post-transplant(180 days)
- To Describe Incidence of Acute Graft Versus Host Disease (GVHD) (II - IV)(100 days post transplant)
- To Describe the Incidence of Grade 3-4 Organ Toxicity(2 years post transplant)
- To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure(at least 2 years post transplant)
- To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant(2 years post transplant)
- To Describe the Pace of Platelet Recovery(180 days post transplant)