Transplantation of Expanded and Unexpanded Umbilical Cord Blood Units Following Myeloablative Chemotherapy for Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Neutrophil Engraftment Within 21 Days
研究概览
简要总结
This study is to evaluate the safety of transplantation of two cord blood products, including toxicities in patients following high-dose, myeloablative chemotherapy for blood malignancies. It is also to determine if the use of two cord products results in an improvement in neutrophil engraftment.
详细描述
The success of BMT as a curative option for patients with malignancies is frequently limited by the inability to identify an appropriate donor in time for transplantation.
Transplantations utilizing umbilical cord blood stem cells are increasingly successful. Data suggest that there are fewer and less developed T-cells in cord products when compared to bone marrow and so are likely to produce less graft-vs.-host disease (GVHD) even in the mismatched setting. In addition, the grafts are easily available second to the ease of collection as compared with other sources such as bone marrow and peripheral blood stem cells (PBSCs). The ability to build cord blood repositories containing samples with HLA types from minorities has and will continue to increase the likelihood of finding suitable products for under represented minorities such as African-Americans, Hispanic populations and mixed ethnic populations.
Unfortunately, limitations remain, secondary to the time to engraftment when the cell dose is less than optimal, resulting in delayed or failed engraftment. In addition, increased cell dose appears to be associated with disease free survival. Therefore, this modality of transplant is generally limited to smaller patients. This protocol evaluates the infusion and engraftment of two cord blood products - one that has been expanded ex vivo and one that has not been expanded following myeloablative chemotherapy for the treatment of hematological malignancies.
Primary Objective:
-To evaluate the safety of transplantation of two cord products including an expanded unit including infusional toxicities and potential immunologic competition.
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 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must have two cord units available. Units must be minimally matched to the subject at 4/6 antigens (HLA Class I (A or B) and Class II (DRB1) - units must have at lease one HLA DRB1 matched allele) and at least one unit must contain a minimum of 1.0 x 107 Total Nucleated Cells /Kg but neither unit may have > 5 x 107Total Nucleated Cells /Kg. (The feasibility of using particular units will be discussed with the Principal Investigators)
- •Disease status precludes waiting to identify a suitably HLA matched unrelated donor
- •Patients must have a diagnosis of one of the following:
- •refractory AML
- •Secondary AML
- •ALL in CR2 with high-risk features such as short CR1 and/or high-risk cytogenetics
- •ALL in CR1 following initial induction failure
- •Acute mixed lineage leukemia
- •CML beyond chronic phase
- •Lymphoma (Hodgkins or Non-Hodgkins) ineligible for Autologous-BMT
- •Myelodysplastic Syndrome
- •Able to provide informed consent or parent/guardian able to provide informed consent.
排除标准
- •Consenting 5/6 or 6/6 HLA matched related donor available
- •Single cord blood product with cell count >5 x10E7 Total Nucleated Cells/kg
- •Poor Performance Status: ECOG performance status >= 2 (Karnofsky or Lansky Play performance<70).
- •Poor Cardiac Function (obtained within 3 weeks of the start of transplant): Left ventricular ejection fraction <= 45% as determined by MUGA or ECHO. For pediatric patients LVEF < 45 % or a Shortening Fraction below normal limits for age.
- •Poor Pulmonary Function (obtained within 3 weeks of the start of transplant):
- •FEV1 and FVC <50% of predicted for patients who have not received thoracic or mantle irradiation.
- •For patients who have received thoracic or mantle irradiation, FEV1 and FVC <= 75% of predicted or DLCO <= 50% of predicted
- •For children unable to perform PFTs second to developmental stage, Pulse oximetry <= 85% on RA
- •Poor Liver Function (obtained within 1 week of the start of transplant): Bilirubin >= 2.0 mg/dl. (with the exception of patients whose hyperbilirubinemia is the result of Gilbert's disease)
- •Poor Renal Function (obtained within 3 weeks of the start of transplant): Corrected CrCl < 60 mg/min. CrCl will be estimated by the Schwartz formula. A measured CrCl or a GFR may be substituted to determine the subject's CrCl
- •HIV Infection: Patients who are HIV positive. (The role of allogenic transplant in HIV+ individuals has not been studied)
- •Pregnancy: Patients who are pregnant. (The chemotherapeutic agents used in bone marrow transplant are teratogenic)
- •Uncontrolled viral, bacterial or fungal infections
- •Patients with symptoms consistent with RSV, influenza A, B or parainfluenza at the time of enrollment on this study will be assayed for the above viruses and if positive are not eligible for the trial until are no longer symptomatic (patients may have continued assay positivity for a period of time post resolution of symptoms second to the nature of the assay)
- •Presence of concomitant medication or incident condition that would create an unreasonable risk for the subject to participate in this study as determined by the investigators (Primary or co-investigators).
- •Patients with known intolerance to or contraindication for any agent that will be used in the subject's proposed myeloablative or required supportive care regimen.
结局指标
主要结局
Neutrophil Engraftment Within 21 Days
时间窗: 21 days
Number of participants who reached 3 consecutive days with ANC \> 500
Number of Participants With Toxicities Related to Infusion of Expanded Cord Blood Products
时间窗: 7 days
次要结局
- Non-relapse Mortality(100 days)