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

Combination Therapy With the Proteasome Inhibitor Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation Trial (PICARD-Lung)

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.

Study Overview

• Status: Completed
• Conditions: Lung Transplant Rejection
• Intervention / Treatment: Drug: Carfilzomib

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 Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Carfilzomib; Carfilzomib will be used in combination with the conventional therapy (plasma exchange and intravenous immunoglobulins); Other Names: Kyprolis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Day 1 to Day 42
Number of Participants With a Decrease in DSA Titer	Number of Participants with a Decrease in DSA Titer.	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.	Day 1 to Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Day 1 to Day 90
Number of Participants With a Decrease in DSA Titer	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	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)	Absolute change in forced expiratory volume in 1 second (FEV1)	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)	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	Day 1 to Day 42
Patient Death Attributable to AMR	Patient death attributable to AMR	Day 1 to Day 90

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-lung Irreversible End-organ Failure	Non-lung irreversible end-organ failure	Day 1 to Day 16
Incidence of Adverse Effects (AE)	Incidence of adverse effects (AE)	Day 1 to Day 16
Incidence of Adverse Effects (AE) Requiring Dose-modification	Incidence of adverse effects (AE) requiring dose-modification	Day 1 to Day 16
Incidence of Hypogammaglobulinemia	Incidence of hypogammaglobulinemia	Day 1 to Day 16
Incidence of Culture-proven de Novo Infection	Incidence of culture-proven de novo infection	Day 1 to Day 42
Diagnosis of Systemic Inflammatory Response Syndrome	Diagnosis of systemic inflammatory response syndrome	Day 1 to Day 16
Patient Death	Patient death	Day 1 to Day 90

Collaborators and Investigators

• Sponsor: John F. McDyer, MD
• Investigators: Principal Investigator: John McDyer, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): November 9, 2020
• Study Completion (Actual): July 26, 2021

Study Registration Dates

• First Submitted: May 21, 2015
• First Submitted That Met QC Criteria: June 15, 2015
• First Posted (Estimate): June 18, 2015

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: March 25, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Carfilzomib; lung transplant; antibody-mediated rejection
• Other Study ID Numbers: PRO15010152

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided