Clinical trial NCT02474927: Combination Therapy With Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation
Official title: Combination Therapy With the Proteasome Inhibitor Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation Trial (PICARD-Lung)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Transplant Rejection
Keywords: antibody-mediated rejection
lung transplant
Carfilzomib
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2015-06-18
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Number of Participants With a Decrease in Titer of One or More DSA (Either Reduced MFI or Absence of DSA on Same Dilution)
timeFrame: Day 1 to Day 42
measure: Number of Participants With a Decrease in DSA Titer
timeFrame: Day 1 to Day 42
measure: Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay
timeFrame: Day 1 to Day 42
Secondary outcomes:
measure: Number of Participants With a Decrease in Titer of One or More DSA (Either Reduced MFI or Absence of DSA on Same Dilution)
timeFrame: Day 1 to Day 90
measure: Number of Participants With a Decrease in DSA Titer
timeFrame: Day 1 to Day 90
measure: Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay
timeFrame: Day 1 to Day 90
measure: Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Day 1 to Day 42
measure: Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Day 1 to Day 90
measure: Presence or Absence of Pathologic Changes Consistent With AMR on Transbronchial Biopsy
timeFrame: Day 1 to Day 42
measure: Patient Death Attributable to AMR
timeFrame: Day 1 to Day 90
Other outcomes:
measure: Non-lung Irreversible End-organ Failure
timeFrame: Day 1 to Day 16
measure: Incidence of Adverse Effects (AE)
timeFrame: Day 1 to Day 16
measure: Incidence of Adverse Effects (AE) Requiring Dose-modification
timeFrame: Day 1 to Day 16
measure: Incidence of Hypogammaglobulinemia
timeFrame: Day 1 to Day 16
measure: Incidence of Culture-proven de Novo Infection
timeFrame: Day 1 to Day 42
measure: Diagnosis of Systemic Inflammatory Response Syndrome
timeFrame: Day 1 to Day 16
measure: Patient Death
timeFrame: Day 1 to Day 90
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: John McDyer, MD
role: PRINCIPAL_INVESTIGATOR
References: