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

NCT ID: NCT03805178

Last Updated: 2019-05-02

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-01
• Study Completion Date: 2020-10-30

Brief Summary

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.

Detailed 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.

Conditions

Lung Transplant Rejection; Antibody-mediated Rejection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rejection post-transplant

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

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: DRUG

Initial phase: 10 mg/kg on days 0 and 4, and again at weeks 2 and 4. Maintenance phase: 10 mg/kg every month beginning 4 weeks after completion of the initial phase.

No dosage adjustments required for renal or hepatic impairment. No known drug interactions for usual post-transplant medication regimen.

Carfilzomib

Intervention Type: DRUG

20mg/m2 Plasmapheresis

Pre-transplant desensitization

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

Group Type: EXPERIMENTAL

Belatacept

Intervention Type: DRUG

Initial phase: 10 mg/kg on days 0 and 4, and again at weeks 2 and 4. Maintenance phase: 10 mg/kg every month beginning 4 weeks after completion of the initial phase.

No dosage adjustments required for renal or hepatic impairment. No known drug interactions for usual post-transplant medication regimen.

Carfilzomib

Intervention Type: DRUG

20mg/m2 Plasmapheresis

Interventions

Belatacept

Initial phase: 10 mg/kg on days 0 and 4, and again at weeks 2 and 4. Maintenance phase: 10 mg/kg every month beginning 4 weeks after completion of the initial phase.

No dosage adjustments required for renal or hepatic impairment. No known drug interactions for usual post-transplant medication regimen.

Intervention Type: DRUG

Carfilzomib

20mg/m2 Plasmapheresis

Intervention Type: DRUG

Other Intervention Names

Nulojix; Kyprolis

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laurie Snyder

Role: PRINCIPAL_INVESTIGATOR

Duke University

Other Identifiers

IM103-407

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Pro00101289

Identifier Type: -

Identifier Source: org_study_id