A Phase I/II Study Evaluating the Safety and Efficacy of Intravenous POL6326 for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Patients With Advanced Hematological Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 2
- 主要终点
- Phase I Study - safety and tolerability of POL6326 as a mobilization agent.
研究概览
简要总结
Determine the safety and tolerability of POL6326 when used as a single mobilization agent.
详细描述
Current protocols use G-CSF to mobilize hematopoietic progenitor cells from matched sibling donors. This process requires from four to six days of G-CSF injection and is associated with significant morbidity, most notably bone pain. POL6326 is associated with few side effects and collection of cells occurs on the same day as POL6326 administration.
This study will evaluate the safety and efficacy of this novel agent for hematopoietic progenitor cell mobilization and allogeneic transplantation based on the following hypotheses:
- Donors mobilized with intravenous POL6326 will require fewer collections than have previously been seen for donors mobilized with subcutaneous plerixafor.
- Healthy HLA-matched donors receiving one or two infusions of POL6326 will mobilize sufficient CD34+ cells (at least 2.0 x 106 CD34+ cells/kg recipient weights) following leukapheresis to support a hematopoietic cell transplant.
- IV POL6326 will result in more rapid kinetics and a higher maximum (peak) of human CD34+ stem cells mobilized from human normal allogeneic donors compared to previous donors who were mobilized with plerixafor.
- The hematopoietic cells mobilized by IV POL6326 will be functional and will result in prompt and durable hematopoietic engraftment following transplantation into HLA-identical siblings with advanced hematological malignancies using various non-myeloablative and myeloablative conditioning regimens and regimens for routine GVHD prophylaxis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older 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
Donor (Phase I and Phase II)
On Day 1 (and possibly Day 2) POL6326 IV Infusion with increasing dose levels in Phase I or with random dose assignment (from the 2 selected from Phase I) in phase II
Leukapheresis collection on Day 1 (and possibly Day 2)
干预措施: POL6326 (Drug)
Donor (Phase I and Phase II)
On Day 1 (and possibly Day 2) POL6326 IV Infusion with increasing dose levels in Phase I or with random dose assignment (from the 2 selected from Phase I) in phase II
Leukapheresis collection on Day 1 (and possibly Day 2)
干预措施: Leukapheresis (Procedure)
Recipient
Day 0 - PBSC transplant with stem cells mobilized with IV POL6326
干预措施: PBSC Transplant (Procedure)
结局指标
主要结局
Phase I Study - safety and tolerability of POL6326 as a mobilization agent.
时间窗: 30 days
Phase II Study - determine the number of allogeneic donors who require a second leukapheresis
时间窗: 2 days
Determine the number of allogeneic donors which collect \>= 2 mill CD34+ cells with one or two leukapheresis procedures treated with IV POL6326. Comparison with historic group of donors who were mobilized with 240 µg/kg SC plerixafor.
次要结局
- Phase I Study - define maximum tolerated dose of POL6326(30 days)
- Phase II Study - pharmacokinetics and pharmacodynamics of IV POL6326(Day 1-3)
- Phase II Study - the proportion of HLA-identical sibling donors who experience grade 3-4 infusional toxicity and the proportion who are safely mobilized(30 days)
- Phase II Study - rate of acute GVHD and chronic GVHD in patients who receive IV POL6326 mobilized peripheral blood stem cells.(Day 100 (+/- 7 days) or Day 365 (+/-14 days))
- Phase II Study - kinetics of neutrophil and platelet engraftment in recipients of POL6326 mobilized peripheral blood stem cells.(Day 365 (+/- 14 days))