- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02474927
Combination Therapy With Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation
March 25, 2022 updated by: John F. McDyer, MD
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
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
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- University of Pittsburgh Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
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.
|
Carfilzomib will be used in combination with the conventional therapy (plasma exchange and intravenous immunoglobulins)
Other Names:
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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)
Time Frame: Day 1 to Day 42
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Number of Participants with a Decrease in titer of one or more DSA (either reduced MFI or absence of DSA on same dilution).
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Day 1 to Day 42
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Number of Participants With a Decrease in DSA Titer
Time Frame: Day 1 to Day 42
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Number of Participants with a Decrease in DSA Titer.
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Day 1 to Day 42
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Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay
Time Frame: Day 1 to Day 42
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Number of Participants with an Absence of one or more previously positive DSA on Cq1 assay.
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Day 1 to Day 42
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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)
Time Frame: Day 1 to Day 90
|
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
Time Frame: Day 1 to Day 90
|
Number of Participants with a Decrease in DSA Titer.
|
Day 1 to Day 90
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Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay
Time Frame: Day 1 to Day 90
|
Number of Participants with an Absence of one or more previously positive DSA on Cq1 assay.
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Day 1 to Day 90
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Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: Day 1 to Day 42
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Absolute change in forced expiratory volume in 1 second (FEV1)
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Day 1 to Day 42
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Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: Day 1 to Day 90
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Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
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Day 1 to Day 90
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Presence or Absence of Pathologic Changes Consistent With AMR on Transbronchial Biopsy
Time Frame: Day 1 to Day 42
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Presence or absence of pathologic changes consistent with AMR on transbronchial biopsy
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Day 1 to Day 42
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Patient Death Attributable to AMR
Time Frame: Day 1 to Day 90
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Patient death attributable to AMR
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Day 1 to Day 90
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Non-lung Irreversible End-organ Failure
Time Frame: Day 1 to Day 16
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Non-lung irreversible end-organ failure
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Day 1 to Day 16
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Incidence of Adverse Effects (AE)
Time Frame: Day 1 to Day 16
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Incidence of adverse effects (AE)
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Day 1 to Day 16
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Incidence of Adverse Effects (AE) Requiring Dose-modification
Time Frame: Day 1 to Day 16
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Incidence of adverse effects (AE) requiring dose-modification
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Day 1 to Day 16
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Incidence of Hypogammaglobulinemia
Time Frame: Day 1 to Day 16
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Incidence of hypogammaglobulinemia
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Day 1 to Day 16
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Incidence of Culture-proven de Novo Infection
Time Frame: Day 1 to Day 42
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Incidence of culture-proven de novo infection
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Day 1 to Day 42
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Diagnosis of Systemic Inflammatory Response Syndrome
Time Frame: Day 1 to Day 16
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Diagnosis of systemic inflammatory response syndrome
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Day 1 to Day 16
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Patient Death
Time Frame: Day 1 to Day 90
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Patient death
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Day 1 to Day 90
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: John McDyer, MD, University of Pittsburgh
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
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
Other Study ID Numbers
- PRO15010152
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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