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

Lung Transplant Rejection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02474927
• Other study ID #: PRO15010152
• Status: Completed
• Phase: Phase 2
• Start date: November 1, 2015
• Est. completion date: July 26, 2021

Study information

• Verified date: March 2022
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: July 26, 2021
• Est. primary completion date: November 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Lung Transplant Rejection

Intervention

Drug:
• Carfilzomib
Carfilzomib will be used in combination with the conventional therapy (plasma exchange and intravenous immunoglobulins)

Locations

Country	Name	City	State
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
John F. McDyer, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Non-lung Irreversible End-organ Failure	Non-lung irreversible end-organ failure	Day 1 to Day 16
Other	Incidence of Adverse Effects (AE)	Incidence of adverse effects (AE)	Day 1 to Day 16
Other	Incidence of Adverse Effects (AE) Requiring Dose-modification	Incidence of adverse effects (AE) requiring dose-modification	Day 1 to Day 16
Other	Incidence of Hypogammaglobulinemia	Incidence of hypogammaglobulinemia	Day 1 to Day 16
Other	Incidence of Culture-proven de Novo Infection	Incidence of culture-proven de novo infection	Day 1 to Day 42
Other	Diagnosis of Systemic Inflammatory Response Syndrome	Diagnosis of systemic inflammatory response syndrome	Day 1 to Day 16
Other	Patient Death	Patient death	Day 1 to Day 90
Primary	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
Primary	Number of Participants With a Decrease in DSA Titer	Number of Participants with a Decrease in DSA Titer.	Day 1 to Day 42
Primary	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	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
Secondary	Number of Participants With a Decrease in DSA Titer	Number of Participants with a Decrease in DSA Titer.	Day 1 to Day 90
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Patient Death Attributable to AMR	Patient death attributable to AMR	Day 1 to Day 90