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

John F. McDyer, MD

Status and phase: Completed; Phase 2

Conditions: Lung Transplant Rejection

Treatments: Drug: Carfilzomib

Study type: Interventional

Funder types: Other

Identifiers

NCT02474927

PRO15010152

Details and patient eligibility

About

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.

Full 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.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 1 patient group

Carfilzomib Treatment Arm

Experimental group

Description:

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.

Treatment:

Drug: Carfilzomib