Combination Therapy With Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation

Phase 2

Completed

• Conditions: Lung Transplant Rejection
• Interventions: Drug: Carfilzomib

• Registration Number: NCT02474927
• Lead Sponsor: John F. McDyer, MD

Brief Summary

The clinical trial is a Phase II open label, single-arm pilot study to evaluate the safety and efficacy of combination therapy with carfilzomib, plasma exchange and intravenous immunoglobulins for AMR after lung transplantation and elucidate important clinical and immunologic phenotypes and mechanisms associated with these outcomes.

Detailed Description

The main objective of the proposed clinical investigation is to evaluate the effects of carfilzomib in addition to conventional therapy on short-term outcomes after the diagnosis of antibody-mediated rejection in lung transplant recipients. In this study, Carfilzomib will be administered at a dose of 20 mg/m2 on two consecutive days, each week for three weeks (Days 1 2, 8, 9, 15, and 16) to constitute one therapeutic cycle. Carfilzomib may be administered for 1-2 complete cycles in the study. Patients will be followed for the duration of their hospital admission after enrollment. Post treatment follow-up will also occur on Days 42 and 90.

Study Timeline

• Study First Submitted: 2015-05-21
• Study First Submitted QC: 2015-06-15
• Study First Posted: 2015-06-18
• Study Start: 2015-11-01
• Primary Completion: 2020-11-09
• Study Completion: 2021-07-26
• Results First Submitted: 2021-11-05
• Status Verified: 2022-03
• Results First Submitted QC: 2022-03-25
• Last Update Submitted: 2022-03-25
• Results First Posted: 2022-04-25
• Last Update Posted: 2022-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• Adult lung transplant recipients ≥ 18 years of age who meet the diagnostic criteria for AMR and who have underwent PFT testing unless intubated and transbronchial biopsy prior to enrollment.

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Exclusion Criteria

• Direct contraindications or previous intolerances to any component of the standard of care regimen including PLEX, 5% human albumin, 5% gammagard S/D or 10% gammagard liquid
• Leukopenia
• Neutropenia
• Thrombocytopenia
• Known Child-Pugh B/C cirrhosis
• Total bilirubin > 4
• ALT > 90
• Known systolic heart failure with LVEF < 40%
• Known pulmonary hypertension
• Any uncontrolled comorbid condition
• Pregnant women
• Breastfeeding women
• Ongoing bacterial or fungal or viral infection that is life-threatening
• Active cytomegalovirus disease
• Active varicella zoster infection
• Previous intolerance to carfilzomib
• Concurrent use of another proteasome inhibitor (e.g., bortezomib)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Carfilzomib Treatment Arm	Carfilzomib	Carfilzomib will be administered at a dose of 20 mg/m2 on two consecutive days, each week for three weeks (Days 1 2, 8, 9, 15, and 16) to constitute one therapeutic cycle. Carfilzomib may be administered for 1-2 complete cycles in the study.

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Decrease in Titer of One or More DSA (Either Reduced MFI or Absence of DSA on Same Dilution)	Day 1 to Day 42	Number of Participants with a Decrease in titer of one or more DSA (either reduced MFI or absence of DSA on same dilution).
Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay	Day 1 to Day 42	Number of Participants with an Absence of one or more previously positive DSA on Cq1 assay.
Number of Participants With a Decrease in DSA Titer	Day 1 to Day 42	Number of Participants with a Decrease in DSA Titer.

Secondary Outcome Measures

Name	Time	Method
Patient Death Attributable to AMR	Day 1 to Day 90	Patient death attributable to AMR
Presence or Absence of Pathologic Changes Consistent With AMR on Transbronchial Biopsy	Day 1 to Day 42	Presence or absence of pathologic changes consistent with AMR on transbronchial biopsy
Number of Participants With a Decrease in Titer of One or More DSA (Either Reduced MFI or Absence of DSA on Same Dilution)	Day 1 to Day 90	Number of Participants with a Decrease in titer of one or more DSA (either reduced MFI or absence of DSA on same dilution).
Number of Participants With a Decrease in DSA Titer	Day 1 to Day 90	Number of Participants with a Decrease in DSA Titer.
Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay	Day 1 to Day 90	Number of Participants with an Absence of one or more previously positive DSA on Cq1 assay.
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)	Day 1 to Day 90	Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)

Trial Locations

Locations (1)

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States