A Phase I-II Open-label Study of UM171 Expanded Cord Blood in a Fed-batch Culture System (UFCB-001) in Patients Who Need an Allogeneic Hematopoietic Stem Cell Transplant But Lack a Suitable Donor
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Monitoring adverse events, toxicities and medical evolution
研究概览
简要总结
Allogeneic hematopoietic stem cell transplantation is a life-saving procedure in patients with blood cancers, but only 25% of transplant candidates have a sibling donor. A matched unrelated donor can be found for 60% of patients but this number is lower for non-Caucasians. Cord blood (CB), another source of stem cells, has major advantages over unrelated donors including immediate availability, better permissiveness in immune mismatches between donor and transplant recipient, better availability for non-Caucasians, and less graft versus host disease, a complication frequently seen after transplant which negatively affects quality of life. Unfortunately, the use of CB is still limited in adults because of the small number of stem cells. UM171, a molecule with hematopoietic stem cell expansion properties, has been shown to increase cord blood stem cells 13 fold. In this trial, Investigators will use UM171 treated CB in patients who need a transplant but lack an acceptable donor.This protocol seeks to test the safety of CB cells expanded with UM171, and to determine the kinetics of engraftment as well as the minimal cord blood unit cell dose that when expanded achieves prompt engraftment.
详细描述
Investigators are proposing a phase I-II, Canadian multi-center, open-label study of UM171 ex vivo expanded CB transplant in 25 patients who need an allogeneic hematopoietic stem cell transplantation (HSCT) but lack a Human Leucocyte Antigen (HLA) matched donor.
Investigators key primary and secondary objectives include:
- To establish the feasibility of expanding cord blood units for allogeneic cord blood transplantation.
- To establish the safety and identify unexpected toxicities associated with the transplantation of cord blood cells expanded with UM171/fed-batch culture system.
- To measure kinetics of neutrophil and platelet recovery.
- To determine minimal cord blood unit cell dose (Total Nucleated Cell (TNC)/CD34+ cells) that when expanded achieves prompt engraftment as a single cord transplant.
Methodology:
Patients with a hematologic malignancy and an indication for allogeneic HSCT who lack a matched unrelated donor will receive a myeloablative or submyeloablative conditioning regimen followed by infusion of UM171 expanded CB graft. Accrual is expected to last 18 months and patients will be followed for 3 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 64 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1
Intervention name: Transplantation of cord blood expanded with UM171 Prethaw CB cell count prior to manipulation: CD34+ cell count 1.0-4.9 x 10E5/kg and TNC superior or equal to 2.0 x 10E7/kg
干预措施: Transplantation of cord blood expanded with UM171 (Biological)
Cohort 2
Intervention name: Transplantation of cord blood expanded with UM171 Prethaw CB cell count prior to manipulation: CD34+ cell count 0.5-4.9 x 10E5/kg and TNC superior or equal to 1.5 x 10E7/kg
干预措施: Transplantation of cord blood expanded with UM171 (Biological)
Cohort 3
Intervention name: Transplantation of cord blood expanded with UM171 Prethaw CB cell count prior to manipulation: CD34+ cell count 0.25-4.9 x 10E5/kg and TNC superior or equal to 1.25 x 10E7/kg
干预措施: Transplantation of cord blood expanded with UM171 (Biological)
结局指标
主要结局
Monitoring adverse events, toxicities and medical evolution
时间窗: up to 36 months post transplant
To identify unexpected toxicities associated with transplantation using cord blood cells expanded with UM171/fed-batch culture system by means of history, physical examination and laboratory evaluation. All adverse events will be evaluated for duration, intensity, and causal relationship with the study medication and followed to the end of the study or until resolution.
次要结局
- Correlation between neutrophil and platelet engraftment and CD34+ and CD34+CD45RA- dose(42 days post transplant)
- Minimal cord blood cell dose that when expanded achieves prompt engraftment(up to 12 months)
- Incidence of backup cord infusion and graft dominance(7, 14, 21, 28, 56, 100 days and at 6 and 12 months)
- Feasibility of cord blood expansion using UM171 (transplant success)(18 months)
- Kinetics of hematopoietic recovery(42 days post transplant)
- B cell evaluation(3, 6, 12, and 18 months)
- Overall survival(100 days an 1,2, 3 years post transplant)
- Incidence of primary and late graft failure(42 days post transplant)
- Incidence of acute and chronic GVHD(through study completion (3 years follow-up))
- T cell evaluation (Cluster of differentiation (CD) 4+ and CD8+)(3, 6, 12, and 18 months)
- progression free survival(100 days an 1,2, 3 years post transplant)
- Incidence of severe infectious complications(through study completion (3 years follow-up))
- Natural Killer (NK) cell evaluation(3, 6, 12, and 18 months)
- Transplant related mortality (TRM)(100 days and 1,2, 3 years post transplant)
- Incidence of engraftment syndrome requiring therapy(24 hours post transplant and during follow-up (3 years))
研究者
Sandra Cohen
MD
Maisonneuve-Rosemont Hospital