Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies (UCAML)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Overall Survival at 100 Days, 1 Year, and 3 Years After Umbilical Cord Blood Transplant in Pediatric Patients.
研究概览
简要总结
In this study, the investigators will use busulfan and cyclophosphamide (BuCy) backbone with the addition of fludarabine as the preparative Stem Cell Transplant (SCT) regimen. As an attempt to improve engraftment rate and reduce infections, the investigators are going to incorporate fludarabine in the conditioning regimen. The use of a BuCy backbone has been widely used and comparable to total body irradiation and cyclophosphamide (Cy/TBI) regimen.
Encouraging data on adding fludarabine to the SCT regimen have been reported. A fludarabine-based, conditioning regimen, with adequate immunosuppressive activity could conceivably allow engraftment of stem cells from alternative donors in hematologic malignancies patients with acceptable engraftment rates and low transplant-related mortality. Regimen-related toxicity is believed to be a major contributing factor to GVHD. Therefore this approach may also lead to reduced GVHD, as some investigators have suggested.
In an attempt to decrease the rate of viral infection and reactivation, the investigators will avoid ATG (Thymoglobulin) / Campath (anti-CD52), and instead administer Mycophenolate Mofetil (MMF). The addition of fludarabine should compensate any increase risk of graft failure with the removal of the ATG/Campath. The investigators anticipate that the removal of ATG/Campath will facilitate immune reconstitution more efficiently after receiving a UCBT.
详细描述
The following will be given as the conditioning regimen for the transplant:
BUSULFAN: Busulfan (intravenous BUSULFEX) dosing will be as follows: patients <12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. Administration and pharmacokinetic monitoring will be performed as per standard practice. Anticonvulsants will be given in accordance with standard Blood and Marrow Transplant Program recommendations.
CYCLOPHOSPHAMIDE: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Mesna will be given in accordance with standard Blood and Marrow Transplant.
FLUDARABINE: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m2. Preparation, administration and monitoring will be according to standard practice procedure
POST-TRANSPLANT IMMUNOSUPPRESSION:
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
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a myeloid hematologic malignancy (acute myelogenous leukemia, secondary myelogenous leukemia or myelodysplastic syndrome) unlikely to be cure by standard chemotherapy. This includes patients who have relapsed after standard chemotherapy treatments and patients in first remission with unfavorable prognostics features.
- •Related or Unrelated Umbilical Cord Blood Unit with 0-1 antigen mismatch at HLA-A and B (at low resolution) and DRB1 (at high resolution), with a total nucleated cell dose of ≥ 4 x 10^7/kg.
- •Lansky/Karnofsky scores at least
- •Written informed consent and/or signed assent line from patient, parent or guardian.
- •Negative pregnancy test, if applicable.
排除标准
- •Patients with uncontrolled infections. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections, patients must be receiving definitive systemic antifungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- •Severe renal disease (Creatinine > 3X normal for age).
- •Severe hepatic disease (direct bilirubin > 3 mg/dL or SGOT > 500).
- •Patient has DLCO < 50% predicted or FEV1 < 50% of predicted, if applicable.
- •Patients with symptomatic cardiac failure unrelieved by medical therapy or evidence of significant cardiac dysfunction by echocardiogram (shortening fraction < 20%).
- •HIV positive.
研究组 & 干预措施
Umbilical Cord Blood Transplant
Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion
干预措施: Busulfan (Drug)
Umbilical Cord Blood Transplant
Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion
干预措施: Cyclophosphamide (Drug)
Umbilical Cord Blood Transplant
Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion
干预措施: Fludarabine (Drug)
Umbilical Cord Blood Transplant
Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion
干预措施: Cord Blood Stem Cell Infusion (Procedure)
结局指标
主要结局
Overall Survival at 100 Days, 1 Year, and 3 Years After Umbilical Cord Blood Transplant in Pediatric Patients.
时间窗: 100 days, 1 year, and 3 years
To determine the overall survival rate at 1 year after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.
次要结局
- Number of Participants With Severe Acute GVHD Grade III-IV(Day 100)
- Number of Participants With Relapse Rate After Transplant(1 and 3 years)
- Number of Participants With Chronic GvHD(1 year)
- Number of Participants With Donor Engraftment After Transplant.(100 days, 6, 9, 12, 24 and 36 months)
- Number of Participants With Platelet Engraftment(Day 180)
- Number of Participants With Neutrophil Engraftment(Day 42)
研究者
Caridad Martinez
Assistant Professor, Pediatric Hematology/Oncology, Center for Cell and Gene Therapy
Baylor College of Medicine