A Pilot Study of Isatuximab in Addition to Standard Therapy for Desensitization or Antibody-mediated Rejection in Lung Transplant Recipients
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Clinical Resolution, as measured by the number of participants with less than 1 episode of Antibody-mediated rejection (AMR)
研究概览
简要总结
The purpose of this study is to determine the safety and feasibility of adding isatuximab to standard of care therapies in patients who will receive a lung transplant, but have significant antibodies against the donor (desensitization), or patients who have previously received a lung transplant and develop antibodies against the donor (antibody-mediated rejection, AMR). The study will compare the impact of isatuximab on the recurrence of antibodies after they have been removed from the blood by a process known as plasmapheresis that is standard of care for this condition. The use of isatuximab in lung transplant recipients is investigational, meaning it is not Food and Drug Administration (FDA) approved for use in lung transplant recipients. This study is a pilot study investigating the feasibility and safety of isatuximab in lung transplant patients. Isatuximab is an FDA approved drug indicated for the treatment of multiple myeloma. It may also be useful for transplant recipients with antibodies against the donor because it eliminates the cells that make antibodies.
详细描述
This dual-arm pilot study will enroll approximately 6 patients undergoing lung transplantation at NYU Langone Health who are either receiving peri-transplant desensitization, or who are admitted for treatment of AMR. All patients will be treated with standard-of-care consisting of plasmaspheresis, IVIG, and rituximab. Additionally, the experimental agent, isatuximab, will be added to this treatment protocol. The patients will first receive 4 weekly doses of isatuximab, followed by 4 bi¬-weekly doses (total 8 doses given over 12 weeks). Patients will be followed with standard-of-care immunologic assessment consisting of weekly DSA assessment and flow cytometry crossmatch (only in the desensitization arm). Additionally, patients undergoing peri-transplant desensitization will have a bone marrow biopsy with pathologic examination and cell counts performed at the time of transplant and repeated at the 30-day bronchoscopy to assess for plasma cell elimination.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cohort A (Desensitization) Inclusion Criteria:
- •Age ≥ 18 years
- •Listed and will receive a lung transplant or multi-organ transplant involving a lung at NYU Langone Health that is deemed to require peri-transplant desensitization
- •Able and willing to provide informed consent
- •Pre-transplant DSA > 5,000 MFI in undiluted serum (measured as individual DSA MFI or as sum of multiple DSAs >1000 MFI in the undiluted serum)
- •Cohort B (AMR) Inclusion Criteria:
- •Age ≥ 18 years
- •Received a lung transplant or multi-organ transplant involving a lung at NYU Langone Health
- •Able and willing to provide informed consent
- •Allograft dysfunction in the setting of at least one of the following criteria:
- •Histopathology suggestive of AMR
- •Lung biopsy demonstrating C4d deposition
- •Positive DSA > 2,000 MFI (as individual DSA MFI)
排除标准
- •Prior or current treatment with rituximab within 6 months of isatuximab administration
- •Prior or current treatment with tocilizumab within 6 months of isatuximab administration
- •Contraindication to isatuximab due to intolerance or hypersensitivity
- •Pregnant or breastfeeding women
- •Known malignancy
- •Active infection without adequate treatment or source control
- •Known hepatitis B viral infection
- •Known HIV infection
研究组 & 干预措施
Peri-transplant desensitization group
Listed and will receive a lung transplant or multi-organ transplant involving a lung at NYU Langone Health that is deemed to require peri-transplant desensitization. Participants will be treated with standard-of-care consisting of plasmaspheresis, IVIG, rituximab and the experimental agent, isatuximab. Patients will be followed with standard-of-care immunologic assessment consisting of weekly DSA assessment and flow cytometry crossmatch (only in the desensitization arm). Additionally, participants will have a bone marrow biopsy with pathologic examination and cell counts performed at the time of transplant and repeated at the 30-day bronchoscopy to assess for plasma cell elimination
干预措施: Isatuximab (Drug)
Peri-transplant desensitization group
Listed and will receive a lung transplant or multi-organ transplant involving a lung at NYU Langone Health that is deemed to require peri-transplant desensitization. Participants will be treated with standard-of-care consisting of plasmaspheresis, IVIG, rituximab and the experimental agent, isatuximab. Patients will be followed with standard-of-care immunologic assessment consisting of weekly DSA assessment and flow cytometry crossmatch (only in the desensitization arm). Additionally, participants will have a bone marrow biopsy with pathologic examination and cell counts performed at the time of transplant and repeated at the 30-day bronchoscopy to assess for plasma cell elimination
干预措施: bone marrow biopsy (Procedure)
Treatment of antibody-mediated rejection
Received a lung transplant or multi-organ transplant involving a lung at NYU Langone Health. Participants will be treated with standard-of-care consisting of plasmaspheresis, IVIG, rituximab and the experimental agent, isatuximab.
干预措施: Isatuximab (Drug)
结局指标
主要结局
Clinical Resolution, as measured by the number of participants with less than 1 episode of Antibody-mediated rejection (AMR)
时间窗: Day 28 (Visit 5)
Participants undergoing desensitization will have stable supplemental oxygen requirement or no supplemental oxygen requirement
Clinical Resolution, as measured by the number of participants with no presence of Donor-specific antibody (DSA)
时间窗: Day 28 (Visit 5)
Participants undergoing desensitization will have no presence of Donor-specific-antibody
Clinical Resolution, as measured by the number of participants with reduction of DSA titer
时间窗: Day 28 (Visit 5)
Participants undergoing desensitization will have no presence of Donor-specific-antibody measured by DSA titer or by C1q assay.
次要结局
- Change in effects of pre-treatment Donor-Specific-Antibodies (DSAs ) with <2000 Mean fluorescent intensity (MFI) at 1:16 dilution(Day 0 (Visit 1), Day 14 (Visit 3), Day 28 (Visit 5), Day 56 (Visit 7), Day 84 (Visit 9))
- Change in effects of pre-treatment Donor-Specific-Antibodies (DSAs ) with 2001-7999 Mean fluorescent intensity (MFI) at 1:16 dilution(Day 0 (Visit 1), Day 14 (Visit 3), Day 28 (Visit 5), Day 56 (Visit 7), Day 84 (Visit 9))
- Change in effects of pre-treatment Donor-Specific-Antibodies (DSAs ) ≥ 8000 Mean fluorescent intensity (MFI) at 1:16 dilution(Day 0 (Visit 1), Day 14 (Visit 3), Day 28 (Visit 5), Day 56 (Visit 7), Day 84 (Visit 9))