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.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Carfilzomib will be used in combination with the conventional therapy (plasma exchange and intravenous immunoglobulins)
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
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 titer of one or more DSA (either reduced MFI or absence of DSA on same dilution).
Time frame: Day 1 to Day 42
Number of Participants With a Decrease in DSA Titer
Number of Participants with a Decrease in DSA Titer.
Time frame: 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 an Absence of one or more previously positive DSA on Cq1 assay.
Time frame: 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 a Decrease in titer of one or more DSA (either reduced MFI or absence of DSA on same dilution).
Time frame: Day 1 to Day 90
Number of Participants With a Decrease in DSA Titer
Number of Participants with a Decrease in DSA Titer.
Time frame: Day 1 to Day 90
Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay
Number of Participants with an Absence of one or more previously positive DSA on Cq1 assay.
Time frame: Day 1 to Day 90
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Absolute change in forced expiratory volume in 1 second (FEV1)
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Time frame: Day 1 to Day 42
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Day 1 to Day 90
Presence or Absence of Pathologic Changes Consistent With AMR on Transbronchial Biopsy
Presence or absence of pathologic changes consistent with AMR on transbronchial biopsy
Time frame: Day 1 to Day 42
Patient Death Attributable to AMR
Patient death attributable to AMR
Time frame: Day 1 to Day 90