Lung Transplant Plasmapheresis (PLEX)/Belatacept/Carfilzomib Protocol for Treatment of Antibody Mediated Rejection (AMR) and Desensitization
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Occurrence of drug side effects
研究概览
简要总结
Antibody mediated rejection (AMR) post transplant contributes to poor long term outcomes after lung transplantation. Additionally, high antibodies detected pre transplant in candidates limit donor availability for lung transplant. This proposal would include belatacept in a multi-therapy regimen. Open label study with two patient cohorts for safety and efficacy of belatacept in a multi-modal protocol. The two patient cohorts are an AMR post-transplant cohort and pre-transplant desensitization cohort. A total of 10 patients will be enrolled.The primary objection is drug tolerability and secondary objectives are antibody measurements and allograft function.
详细描述
Antibody mediated rejection (AMR) post transplant contributes to poor long term outcomes after lung transplantation. Additionally, high antibodies detected pre transplant in candidates limit donor availability for lung transplant. Multimodal therapies with rituximab, intravenous immunoglobulin, plasmapheresis and proteasome inhibitors have not significantly altered the antibodies in these patients. Belatacept targets the T and B cell interaction such that it represents a novel therapeutic strategy. This proposal would include belatacept in a multi-therapy regimen.
This is an open label study with two patient cohorts for safety and efficacy of belatacept in a multi-modal protocol. The two patient cohorts are an AMR post-transplant cohort and pre-transplant desensitization cohort. A total of 10 patients will be enrolled.The primary objection is drug tolerability and secondary objectives are antibody measurements and allograft function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Inclusion criteria for the AMR post-transplant cohort
- •Positive DSAs and allograft dysfunction defined by changes in pulmonary physiology, gas exchange, radiological features or deteriorating functional performance that is highly suspicious for AMR
- •Recipient is Epstein-Barr virus positive (EBV+) by serology
- •Ability to provide signed and dated IRB approved written consent in accordance with regulatory and institutional guidelines prior to any protocol-related procedure
- •Inclusion criteria for the pre-transplant desensitization cohort
- •Elevated HLA antibodies (defined as MFI >1000) such that the calculated panel reactive antibodies are >60%
- •At least 2 HLA antibodies with Mean Fluorescent Intensity (MFI) <10,000 and at least 2 HLA antibodies with MFI <5,000 on undiluted serum that do not demonstrate an increase in MFI with dilution at 1:16 (no evidence of a prozone effect).
- •EBV+ by serology
- •Clinically stable defined by not on invasive mechanical ventilation, extracorporeal membrane oxygenation support or other invasive life support requiring ICU level of care
- •Ability to provide signed and dated IRB approved written consent in accordance with regulatory and institutional guidelines prior to any protocol-related procedure
- •Exclusion criteria for both AMR post-transplant cohort and pre-transplant cohort
- •Active systemic infection
- •Allergy to carfilzomib or belatacept
- •Known malignancy in the previous 2 years except for non-melanomatous skin cancer
- •Pregnancy
- •Inability to commit to complete treatment protocol at Duke as all procedures must be completed at Duke
- •Prisoners or those who are compulsory detained
排除标准
- 未提供
研究组 & 干预措施
Rejection post-transplant
Treatment with Belatacept and Carfilzomib for subjects who show evidence of antibody-mediated rejection (AMR) following lung transplantation.
干预措施: Belatacept (Drug)
Rejection post-transplant
Treatment with Belatacept and Carfilzomib for subjects who show evidence of antibody-mediated rejection (AMR) following lung transplantation.
干预措施: Carfilzomib (Drug)
Pre-transplant desensitization
Treatment with Belatacept and Carfilzomib for subjects with elevated human leukocyte antigen (HLA) antibodies prior to lung transplantation.
干预措施: Belatacept (Drug)
Pre-transplant desensitization
Treatment with Belatacept and Carfilzomib for subjects with elevated human leukocyte antigen (HLA) antibodies prior to lung transplantation.
干预措施: Carfilzomib (Drug)
结局指标
主要结局
Occurrence of drug side effects
时间窗: Within 28 days of last administration of study drugs
Drug tolerability with respect to freedom from drug side effects measured using descriptive statistics
Occurrence of infection
时间窗: Within 28 days of last administration of study drugs
Drug tolerability with respect to freedom from infection measured using descriptive statistics
Occurrence of malignancy
时间窗: Within 28 days of last administration of study drugs
Drug tolerability with respect to freedom from malignancy measured using descriptive statistics
次要结局
- Number of subjects in the AMR cohort with resolution of at least one donor specific human leukocyte antigen (HLA) antibody (DSA)(Within 4 weeks of completion of treatment)
- Number of subjects in the AMR cohort with decrease in DSA by one log(Within 4 weeks of completion of treatment)
- Number of subjects in the transplant desensitization cohort with elimination of non-DSA HLA antibodies at 1:16 dilution(Within 4 weeks of completion of treatment)
- Number of subjects in the AMR cohort with improvement or stabilization of lung function as measured by spirometry data(Within 4 weeks of completion of treatment)
- Number of subjects in the AMR cohort with improvement in oxygenation as measured by Liters/min oxygen at rest(Within 4 weeks of completion of treatment)
- Number of subjects in the AMR cohort with elimination of DSA at 1:16 dilution(Within 4 weeks of completion of treatment)
- Number of subjects in the transplant desensitization cohort with decrease in non-DSA HLA antibodies by one log(Within 4 weeks of completion of treatment)