The Safety and Efficacy of Prophylactic Defibrotide Administration in Children, Adolescents, and Young Adults With Sickle Cell Disease or Beta Thalassemia Following Myeloablative Conditioning (MAC) and Haploidentical or Matched Unrelated Donor (MUD) Stem Cell Transplantation Utilizing CD34 Enrichment and T-Cell (CD3) Addback
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 5
- 主要终点
- All patients will be monitored for the development of SOS.
研究概览
简要总结
This is a follow-up trial to NYMC 526 (NCT01461837) to assess the safety, efficacy and toxicity of administering Defibrotide prophylaxis for high-risk sickle cell or beta thalassemia patients undergoing a familial haploidentical or MUD allogeneic stem cell transplantation with CD34 enrichment and T-cell addback. This patient population historically has a risk of developing sinusoidal obstructive syndrome (SOS) and Defibrotide has demonstrated efficacy in treatment of SOS. The Funding Source is FDA OOPD.
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
- 6 Months 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Disease: Homozygous Hemoglobin S Disease, or Hemoglobin S B0/+ thalassemia, or Hemoglobin SC Disease, or Beta thalassemia intermedia/majora
- •Patients must demonstrate one or more of the following Sickle Cell Disease Complications
- •Clinically significant neurologic event (stroke) or any neurologic deficit lasting >24 hours that is accompanied by an infarct on cerebral MRI
- •Acute chest syndrome in the preceding two year period prior to enrollment that have failed, been non-compliant or declined hydroxyurea treatment, or prior to chronic RBC transfusion therapy, exchange transfusion or erythrocyte pheresis.
- •Recurrent painful events (at least 3 in the 2 years prior to enrollment or prior to chronic RBC transfusion therapy, exchange transfusion or erythrocyte pheresis).
- •Abnormal TCD study requiring starting on chronic transfusion therapy and/or exchange transfusions.
- •At least one silent infarct lesion on a MRI scan of the head. Or (directly or probably related to SCD)
- •Sickle Cell nephropathy;
- •Splenic sequestration requiring RBC transfusion;
- •Aplastic crisis requiring RBC transfusion;
- •Avascular necrosis of the hip diagnosed by MRI;
- •Two episodes or more of leg ulcerations;
- •Recurrent priapism .
- •Infant dactylitis.
- •all patients must meet disease, age, organ function and donor criteria;
排除标准
- •Patients who are receiving concomitant systemic anticoagulants and/or fibrinolytic therapies.
- •Patients with a previously known hypersensitivity reaction to defibrotide.
- •Females who are pregnant or breast-feeding are not eligible
- •Patients with documented uncontrolled infection at the time of study entry are not eligible.
- •Patients who have an unaffected HLA matched sibling donor willing to proceed to donation will not be eligible for this study.
- •Karnofsky or Lansky (age appropriate) Performance Score <50% (hemiplegia alone secondary to a previous stroke is not an exclusion)
- •Demonstrated lack of compliance with medical care.
- •Patients with clinically significant fibrosis or cirrhosis of the liver will not be eligible.
- •Patients who have previously received a HSCT will not be eligible.
- •Patients with contraindications to the use of defibrotide
研究组 & 干预措施
Defibrotide prophylaxis
defibrotide will be given prior to and during myeloablative immunotherapy conditioning (MAIC) followed by familial haploidentical (FHI) allogeneic stem cell transplantation (AlloSCT) with CD34 enrichment and t-cell addback in patients with high-risk sickle cell disease or beta thalassemia to reduced the risk and rate of the development of sinusoidal obstructive syndrome (SOS).
干预措施: Defibrotide (Drug)
结局指标
主要结局
All patients will be monitored for the development of SOS.
时间窗: 1 year
All patients will get daily lab values while in patients and then as needed to monitor for elevation in liver function tests and other abnormal chemistry or hematology values. Imaging on the liver will be performed as needed to determine if they develop SOS with defibrotide.
All patients will be monitored for known and unknown side effects of defibrotide with daily physical exams while in the hospital and then as needed in addition to daily laboratory values including chemistries, hematology labs as needed
时间窗: 100 days
Patients will be given Defibrotide prophylaxis starting 10 days before the stem cell infusion at 6.25 mg/kg IV q6h and continue through Day +21.
次要结局
未报告次要终点
研究者
Mitchell Cairo
Principal Investigator
New York Medical College