Emapalumab for the Prevention of Graft Rejection in Hematopoietic Stem Cell Transplant (HSCT) Recipients
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 20
- 主要终点
- Preliminary efficacy of Emapalumab
研究概览
简要总结
The investigators hypothesize that graft rejection after hematopoietic stem cell transplant (HSCT) is primarily driven by interferon gamma, and prophylactic interferon gamma inhibition in high-risk patients will prevent graft rejection. Additionally, knowledge of emapalumab PK/PD and in vitro mechanistic effects of emapalumab in this novel setting will guide optimization of dosing regimens and treatment approaches in future studies.
详细描述
Graft rejection is a devastating and understudied complication of hematopoietic stem cell transplant (HSCT) due to the lack of available interventions outside of re-transplantation. Re-transplantation is challenging and is associated with increased morbidity and mortality.
The purpose of this study is to learn more about emapalumab and its ability to prevent graft rejection in hematopoietic stem cell transplant (HSCT) recipients. Specifically, the study doctors would like to learn more about the efficacy and treatment of emapalumab as a prophylactic intervention for graft rejection.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients undergoing allogeneic HSCT at our institution will be evaluated for graft rejection risk factors. Patients deemed high risk for graft rejection will have 2 or more of the following: mismatched or haploidentical donor, ex vivo t-cell depleted graft, prior history of graft rejection.
排除标准
- •Known hypersensitivity to any constituent of the study medication.
研究组 & 干预措施
Emapalumab 3 mg/kg
Patients randomized to this arm will receive 3mg/kg of emapalumab intravenously (IV) once on day +1 after HSCT. Up to two additional, 10mg/kg rescue doses may be administered if patients developed signs and symptoms of acute graft rejection. Rescue dose administration decisions will be made in consultation with the lead study investigator. Emapalumab is a ligand-based therapy, which means high levels of circulating ligand (i.e. interferon gamma) will rapidly consume the drug. For these reasons, rescue doses may be given as early as 24 hours from the prior dose.
干预措施: Emapalumab 3 mg/kg (Drug)
Emapalumab 10 mg/kg
Patients randomized to this arm will receive 10mg/kg of emapalumab intravenously (IV) once on day +1 after HSCT. Up to two additional, 10mg/kg rescue doses may be administered if patients developed signs and symptoms of acute graft rejection. Rescue dose administration decisions will be made in consultation with the lead study investigator. Emapalumab is a ligand-based therapy, which means high levels of circulating ligand (i.e. interferon gamma) will rapidly consume the drug. For these reasons, rescue doses may be given as early as 24 hours from the prior dose.
干预措施: Emapalumab 10 mg/kg (Drug)
结局指标
主要结局
Preliminary efficacy of Emapalumab
时间窗: 100 days
Measured by the incidence of graft rejection in the treatment cohort.
次要结局
- Number of patients who develop infections(100 days after HSCT.)
- Number of patients who develop mixed chimerism.(100 days after HSCT.)
- Maximum plasma concentration (Cmax) of emapalumab after 10 mg/kg prophylactic dosing(Until day 42 or time of rescue dose, whichever is sooner)
- Maximum plasma concentration of emapalumab after 3 mg/kg prophylactic dosing(Until day 42 or time of rescue dose, whichever is sooner)
- Maximum plasma concentration of emapalumab after rescue dosing(Until day 42 or 1 week after rescue dose, whichever is later)
- Number of patients in 10 mg/kg prophylactic dosing arm who maintain CXCL9 levels below the upper limit of normal for the test (</= 647 pg/mL).(Until day 42 or 1 week after rescue dose, whichever is later)
- Number of patients in 3 mg/kg prophylactic dosing arm who maintain CXCL9 levels below the upper limit of normal for the test (</= 647 pg/mL).(Until day 42 or 1 week after rescue dose, whichever is later)
- Number of patients in 10 mg/kg prophylactic dosing arm who maintain CXCL9 levels below 2.6x the upper limit of normal for the test.(Until day 42 or 1 week after rescue dose, whichever is later)
- Number of patients in 3 mg/kg prophylactic dosing arm who maintain CXCL9 levels below 2.6x the upper limit of normal for the test.(Until day 42 or 1 week after rescue dose, whichever is later)
- Emapalumab half-life after 10 mg/kg prophylactic dosing(Until day 42 or time of rescue dose, whichever is sooner)
- Emapalumab half-life after 3 mg/kg prophylactic dosing(Until day 42 or time of rescue dose, whichever is sooner)
- Emapalumab half-life after 10mg/kg rescue dosing(Until day 42 or time of rescue dose, whichever is sooner)
- Overall survival(100 days after HSCT.)