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

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.

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.

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)