Lung Transplant Plasmapheresis/Belatacept/Carfilzomib for Antibody Mediated Rejection and Desensitization

Duke University

Status and phase: Withdrawn; Phase 2

Conditions: Antibody-mediated Rejection; Lung Transplant Rejection

Treatments: Drug: Carfilzomib; Drug: Belatacept

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03805178

Pro00101289

IM103-407 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

Rejection post-transplant

Experimental group

Description:

Treatment with Belatacept and Carfilzomib for subjects who show evidence of antibody-mediated rejection (AMR) following lung transplantation.

Treatment:

Drug: Belatacept

Drug: Carfilzomib

Pre-transplant desensitization

Experimental group

Description:

Treatment with Belatacept and Carfilzomib for subjects with elevated human leukocyte antigen (HLA) antibodies prior to lung transplantation.

Treatment:

Drug: Belatacept

Drug: Carfilzomib