A Phase Ib Treatment Trial Using AbGn-168H to Treat Steroid Refractory Acute Graft-vs.-Host Disease (aGVHD) in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Cytokine release syndrome or acute infusion reactions
研究概览
简要总结
This study is to establish the safety, determine if there is an improvement in steroid refractory acute graft-vs-host disease (aGvHD) compared to historical cohorts, and determine the changes of aGvHD-associated T-cell clones in patients with steroid-refractory aGVHD following allogeneic hematopoietic cell transplantation administered AbGn-168H once weekly for 4 weeks.
详细描述
AbGn-168H is a humanized monoclonal antibody. This is a dose escalation study using a modified toxicity probability interval method. AbGn-168H will be administered intravenously (IV) once weekly for four weeks, in patients with steroid refractory aGVHD following hematopoietic cell transplant (HCT). After completion of study treatment, patients are followed up for 90 days.The primary objective of this study is to establish the safety, and the secondary objectives of this study are to determine if there is an improvement in disease response at 3 months after diagnosis of steroid refractory aGVHD compared to historical cohorts and to determine the changes in frequency and/or phenotype of aGVHD-associated T cell clones in response to AbGn-168H therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Diagnosis of skin, gut and/or liver steroid-refractory GVHD by clinical assessment of treating physician following allogeneic HCT. Patients who fail to respond to steroids by 7 days are considered steroid-refractory
- •Previously-treated with any conditioning regimen and any GVHD immune suppression prophylaxis and formulation of steroids, except as noted in Exclusion Criteria #
- •AbGn-168H (neihulizumab) therapy can begin not more than 14 days after diagnosis of aGvHD
- •Karnofsky Performance Status (KPS) > 50%
- •No evidence of HCT graft failure or multi-organ failure
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Uncontrolled infections not responsive to antimicrobial therapy requiring intensive critical care
- •Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy
- •Treatment with investigational GVHD prophylactic agents (eg, CCR5 inhibitors; lenalidomide; and/or bortezomib) within the 7 days prior to the 1st dose of neihulizumab
- •Treatment with other investigational agents within the prior 7 days prior to the 1st dose of AbGn-168H (neihulizumab)
- •CMV PCR > 500 copies/mL or evidence of end-organ damage due to CMV
- •Pregnant or nursing
- •HIV positivity (NOTE: patients positive for hepatitis B or hepatitis C are not excluded, and may be evaluated on a case-by-case basis)
- •Renal clearance CCR < 40 mL/min
结局指标
主要结局
Cytokine release syndrome or acute infusion reactions
时间窗: Within 24 hours after study drug infusion
Grade 3 to 5 cytokine release syndrome or acute infusion reactions
Adverse events
时间窗: On or before study day 52
Grade 3 to 5 adverse events considered at least possibly-related to neihulizumab
All-cause mortality
时间窗: Within 7 days of infusion
Grade 5 all-cause mortality
Neutropenia
时间窗: Duration of study
Grade 4 neutropenia lasting more than 14 days considered at least possibly related to study drug
次要结局
- Changes in frequency and/or phenotype of aGVHD-associated T-cell clones(At time of diagnosis up to 90 days)
- GVHD treatment response as measured by the Modified Keystone aGVHD clinical grade scale(At 90 days after the diagnosis of aGVHD)