Combination Therapy With the Proteasome Inhibitor Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation Trial (PICARD-Lung)
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- Number of Participants With a Decrease in Titer of One or More DSA (Either Reduced MFI or Absence of DSA on Same Dilution)
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Arms & Interventions
Carfilzomib Treatment Arm
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.
Intervention: Carfilzomib (Drug)
Outcomes
Primary Outcomes
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 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
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 a Decrease in DSA Titer
Time Frame: Day 1 to Day 42
Number of Participants with a Decrease in DSA Titer.
Secondary Outcomes
- Patient Death Attributable to AMR(Day 1 to Day 90)
- Presence or Absence of Pathologic Changes Consistent With AMR on Transbronchial Biopsy(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)(Day 1 to Day 90)
- Number of Participants With a Decrease in DSA Titer(Day 1 to Day 90)
- Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay(Day 1 to Day 90)
- Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)(Day 1 to Day 90)
Investigators
John F. McDyer, MD
Associate Professor of Medicine
University of Pittsburgh