Belimumab for Treatment of Chronic Graft-versus-Host Disease Following Allogeneic Hematopoietic Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Overall response rate of chronic GvHD after belimumab treatment
研究概览
简要总结
Given the role of B cells in the pathophysiology of chronic graft versus host disease (GvHD), the association between elevated BAFF levels post-transplant in abnormal B-cell homeostasis and chronic GvHD, and the efficacy of belimumab in the inhibition of soluble human B lymphocyte stimulator protein (BAFF) signaling, these proof-of-principle findings support the rational for use of belimumab as treatment of chronic GvHD.The investigators propose a pilot and feasibility study to assess the safety and tolerability, as well as preliminary efficacy, of belimumab a treatment of cGvHD following allogeneic hematopoietic cell transplantation (alloHCT). The investigators' central hypothesis is that belimumab will be well tolerated and have a favorable effect on chronic GvHD,and we explored therapeutic dosage of belimumab.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.18 to 65years old 2.Newly diagnosed, moderate or severe chronic GvHD according to the 2014 NIH Consensus Criteria, requiring systemic immunosuppression 3.Karnofsky performance status greater than or equal to 60% 4.History of prior alloHSCT; any donors, conditioning regimens and graft sources are allowed 5.Newly diagnosed moderate or severe chronic Graft versus Host Disease (GvHD) (according to the 2014 NIH Consensus Criteria, requiring systemic immunosuppression 6.History of prior allogeneic Hematopoietic Stem Cell Transplant (HSCT) (any donors, conditioning regimens and graft sources are allowed).
- •7.Stable doses of other immunosuppressive medications (e.g., calcineurin inhibitors, mycophenolate mofetil, rapamune, etc.) with no dose increase in the 2 weeks prior to study treatment initiation. Doses may be adjusted for trough levels.
- •8.Patients tested positive for autoantibodies (ANA titer ≥1:80) and high BAFF levels (plasma concentration ≥15ng/ml).
- •9.Laboratory parameters as defined below: Serum creatinine less than or equal to 2.0 x ULN AST and ALT less than or equal to 3 x ULN (less than or equal to 5 x ULN if unequivocal liver GvHD) Total bilirubin less than or equal to 3 x ULN 10.Ability to understand and willingness to sign a written informed consent fo
排除标准
- •Relapsed or progressive malignant disease (other than minimal residual disease)
- •History of other malignant diseases, including post-transplant lymphoproliferative disease
- •Rituximab or other anti-B cell-specific antibodies were used in the past 3 months.
- •Uncontrolled infections (including prior aspergillosis) not responsive to antibiotics, antiviral medicines, or antifungal medicines
- •Donor lymphocyte transfusion for donor chimeric relapse or loss.
- •Any other reason at the discretion of the investigators and documented in the medical record that may raise concerns about the subject safety or ability to participate on this study -
研究组 & 干预措施
Low-dose group of Belimumab
Belimumab 1mg/kg com combined with conventional therapy
干预措施: Belimumab (Benlysta) (Drug)
High-dose group of Belimumab
Belimumab 4mg/kg com combined with conventional therapy
干预措施: Belimumab (Benlysta) (Drug)
结局指标
主要结局
Overall response rate of chronic GvHD after belimumab treatment
时间窗: approximately 6 months
cGVHD grade according NIH
次要结局
- Duration of response rate of chronic GvHD after belimumab treatment(12 months)
研究者
xuna
professor
Nanfang Hospital, Southern Medical University