CD40-L Blockade for Prevention of Acute Graft-Versus-Host Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 3
- 主要终点
- Incidence of Grade II-IV Acute Graft-versus Host Disease
研究概览
简要总结
The purpose of this study is to examine the safety and efficacy of the addition of BMS-986004 to standard of care Sirolimus (SIR)-based immune suppression.
详细描述
The approach builds upon extensive evidence supporting the benefit of CD40L blockade in disrupting key signaling events associated with immune activation. The trial addresses a pressing clinical need, namely prevention of Graft-Versus-Host Disease (GVHD) after hematopoietic cell transplantation (HCT) and promotion of donor-recipient immune tolerance. The safety profile of this anti-CD40L antibody overcomes major prior limitations, and the planned biologic studies will provide significant mechanistic insight.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 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
- •Hematologic malignancy or blood disorder requiring allogeneic HCT
- •Adequate vital organ function as defined per protocol
- •Karnofsky Performance Status Score (KPS) ≥ 80%
- •Participants must have an available 8/8 HLA-A, -B, -C, and -DRB1 matched-related or unrelated donor
排除标准
- •Active infection not controlled with appropriate antimicrobial therapy
- •HIV, hepatitis B or C infection or known history of HIV, hepatitis B or C(all patients will be tested for HIV, hepatitis B and C as part of standard pre-transplant testing, and will be excluded from this trial if positive)
- •Anti-thymocyte globulin, or cyclophosphamide administered within 14 days before or planned to receive with HCT conditioning or as part of GVHD prophylaxis in the 14 days after HCT
- •Known allergic reactions to components of the study drug
- •Concurrent treatment with another investigational drug
- •History of thromboembolism, transient ischemic attack, stroke, myocardial infarction within 3 months preceding the transplant, or uncontrolled congestive heart failure or cardiac arrhythmias.
- •Post-transplant maintenance therapies such as FLT3 inhibitor, tyrosine kinase inhibitor, JAK inhibitors etc. are not allowed if plan is to initiate such therapies <90 days post-transplant. Patient will be eligible if plan to initiate maintenance therapy is after day 90 post-transplant.
研究组 & 干预措施
Combination Therapy
BMS-986004: From day 13, intravenously (IV) every 2 week through day 100 post HCT.
Tacrolimus: From day -3 as standard of care. Sirolimus: From day -1 as standard of care.
干预措施: BMS-986004 (Drug)
Combination Therapy
BMS-986004: From day 13, intravenously (IV) every 2 week through day 100 post HCT.
Tacrolimus: From day -3 as standard of care. Sirolimus: From day -1 as standard of care.
干预措施: Sirolimus (Drug)
Combination Therapy
BMS-986004: From day 13, intravenously (IV) every 2 week through day 100 post HCT.
Tacrolimus: From day -3 as standard of care. Sirolimus: From day -1 as standard of care.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Incidence of Grade II-IV Acute Graft-versus Host Disease
时间窗: 1 year post HCT
Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) by day 100 after hematopoietic cell transplantation (HCT). Acute GVHD severity will be determined by standard Consensus Criteria, and the cumulative incidence of grade II-IV acute GVHD will be reported through day 100 post-HCT, with relapse and death as competing risk events.
次要结局
- Chronic Graft-versus Host Disease Through 1 Year Post HCT(1 year post HCT)
- Malignancy Relapse Post-HCT(1 year post HCT)
- Non-relapse Mortality(1 year post HCT)
- Overall Survival (OS)(1 year post HCT)