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

NCT03805178 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: Pro00101289IM103-407
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Lung Transplant Rejection; Antibody-mediated Rejection

Outcome Measures

Primary Outcomes (3)

• Occurrence of drug side effects

  Drug tolerability with respect to freedom from drug side effects measured using descriptive statistics

  Within 28 days of last administration of study drugs

• Occurrence of infection

  Drug tolerability with respect to freedom from infection measured using descriptive statistics

  Within 28 days of last administration of study drugs

• Occurrence of malignancy

  Drug tolerability with respect to freedom from malignancy measured using descriptive statistics

  Within 28 days of last administration of study drugs

Secondary Outcomes (7)

• 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 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 decrease in DSA by one log

  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

Study Arms (2)

Rejection post-transplant

EXPERIMENTAL

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

Drug: Belatacept; Drug: Carfilzomib

Pre-transplant desensitization

EXPERIMENTAL

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

Drug: Belatacept; Drug: Carfilzomib

Interventions

Belatacept 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.

Also known as: Nulojix

Pre-transplant desensitization; Rejection post-transplant

Carfilzomib DRUG

20mg/m2 Plasmapheresis

Also known as: Kyprolis

Pre-transplant desensitization; Rejection post-transplant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Bristol-Myers Squibb: collaborator

MeSH Terms

Interventions

Abatacept; carfilzomib

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Laurie Snyder

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2019
• First Posted: January 15, 2019
• Study Start: May 1, 2019
• Primary Completion: August 1, 2020
• Study Completion: October 30, 2020
• Last Updated: May 2, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share