A Phase I/II Study of Intentionally Mis-Matched, Allogeneic Th1 Memory Cells (AlloStim) Conjugated With CD3/CD28-coated Microbeads in Patients With Relapsed or Refractory Hematological Malignancy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Determination of toxicity related to AlloStim infusion in accordance with NCI Common Toxicity Criteria v.3
研究概览
简要总结
The purpose of this study is to determine the safety and anti-tumor effects of an experimental immunotherapy drug, called AlloStim, which is intentionally mis-matched immune cells which are designed to elicit the same anti-tumor mechanism that occurs in allogeneic bone marrow/stem cell mini-transplant (BMT) procedures, without the toxicity associated with graft vs. host disease (GVHD).
详细描述
AlloStim is combination biological drug and medical device formulation consisting of allogeneic immune cells that have been expanded and differentiated ex-vivo. These cells are conjugated to monoclonal antibody coated microparticles prior to infusion. The immune cells are living CD4+ memory Th1-like T-cells (T-Stim) that are differentiated from precursors purified from normal donor blood. AlloStim is a composition of T-Stim cells conjugated to paramagnetic epoxy covered microparticles (4.5micron) with covalently bound anti-CD3/anti-CD28 monoclonal antibodies (Dynabeads® ClinExVivo™ CD3/CD28) at a 2:1 bead:cell ratio. The T-Stim cells are intentionally mismatched to the recipient.
The graft vs. tumor (GVT) effect that occurs after allogeneic bone marrow transplant (BMT) is a curative therapy for advanced hematological malignancy but the clinical application of GVT is severely limited by graft vs. host disease (GVHD) toxicity. AlloStim is designed to elicit the "mirror" of the GVT/GVHD effects in the host immune system. Rather than trying to separate these effects, we have proposed that the effects could remain associated and "mirrored" onto the host immune system creating linked host vs. tumor (HVT) and host vs. graft (HVG) effects. We hypothesized that allogeneic Th1 memory cells activated at time of infusion to produce type 1 cytokines and express CD40L would elicit HVT/HVG "mirror effects" in immunocompetent cancer patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •histologically confirmed hematological malignancy
- •unresponsive to chemotherapy and/or recurrence after autologous transplant
- •adequate kidney, liver, lung and heart function
排除标准
- •prior allogeneic transplant
- •immunosuppressive therapy for concurrent medical condition
- •active viral infection
结局指标
主要结局
Determination of toxicity related to AlloStim infusion in accordance with NCI Common Toxicity Criteria v.3
时间窗: Within first 48 hours post infusion, at 30 days and at 60 days post infusion
次要结局
- Evaluation and reporting of anti-tumor response will be conducted in accordance with internationally accepted criteria for the disease indication being evaluated(30 days and 60 days post infusion and yearly thereafter)
- Immunological Response(30 days, 60 days)