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

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ClinicalTrials.gov Identifier: NCT02474927
Recruitment Status : Recruiting
First Posted : June 18, 2015
Last Update Posted : June 15, 2018
Sponsor:
Information provided by (Responsible Party):
John F. McDyer, MD, University of Pittsburgh

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.

Condition or disease Intervention/treatment Phase
Lung Transplant Rejection Drug: Carfilzomib Phase 2

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  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Combination Therapy With the Proteasome Inhibitor Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation Trial (PICARD-Lung)
Study Start Date : November 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


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 Name: Kyprolis




Primary Outcome Measures :
  1. Absolute change in DSA strength, titer, and complement fixation [ Time Frame: Day 1 to Day 42 ]

Secondary Outcome Measures :
  1. Absolute change in DSA strength, titer, and complement fixation [ Time Frame: Day 1 to Day 90 and Day 42 to Day 90 ]
  2. Absolute change in forced expiratory volume in 1 second (FEV1) [ Time Frame: Day 1 to Day 42 and to Day 90 ]
  3. Presence or absence of pathologic changes consistent with AMR on transbronchial biopsy [ Time Frame: Day 1 to Day 42 ]
  4. Patient death attributable to AMR [ Time Frame: Day 1 to Day 90 ]

Other Outcome Measures:
  1. Non-lung irreversible end-organ failure [ Time Frame: Day 1 to Day 16 ]
  2. Incidence of adverse effects (AE) [ Time Frame: Day 1 to Day 16 ]
  3. Incidence of adverse effects (AE) requiring dose-modification [ Time Frame: Day 1 to Day 16 ]
  4. Incidence of hypogammaglobulinemia [ Time Frame: Day 1 to Day 16 ]
  5. Incidence of culture-proven de novo infection [ Time Frame: Day 1 to Day 42 ]
  6. Diagnosis of systemic inflammatory response syndrome [ Time Frame: Day 1 to Day 16 ]
  7. Patient death [ Time Frame: Day 1 to Day 90 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02474927


Contacts
Contact: Christopher Ensor, PharmD 412-383-1327 chris.ensor@pitt.edu

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
John F. McDyer, MD
Investigators
Principal Investigator: John McDyer, MD University of Pittsburgh

Responsible Party: John F. McDyer, MD, Associate Professor of Medicine, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02474927     History of Changes
Other Study ID Numbers: PRO15010152
First Posted: June 18, 2015    Key Record Dates
Last Update Posted: June 15, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by John F. McDyer, MD, University of Pittsburgh:
antibody-mediated rejection
lung transplant
Carfilzomib

Additional relevant MeSH terms:
Antibodies
Immunoglobulins
Proteasome Inhibitors
Immunologic Factors
Physiological Effects of Drugs
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action