NCT02474927

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
22

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Nov 2015

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 21, 2015

Completed
28 days until next milestone

First Posted

Study publicly available on registry

June 18, 2015

Completed
5 months until next milestone

Study Start

First participant enrolled

November 1, 2015

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 9, 2020

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 26, 2021

Completed
9 months until next milestone

Results Posted

Study results publicly available

April 25, 2022

Completed
Last Updated

April 25, 2022

Status Verified

March 1, 2022

Enrollment Period

5 years

First QC Date

May 21, 2015

Results QC Date

November 5, 2021

Last Update Submit

March 25, 2022

Conditions

Lung Transplant Rejection

Keywords

antibody-mediated rejectionlung transplantCarfilzomib

Outcome Measures

Primary Outcomes (3)

  • 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 Outcomes (7)

  • 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

    Day 1 to Day 90

  • 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)

    Day 1 to Day 42

  • Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)

    Day 1 to Day 90

  • +2 more secondary outcomes

Other Outcomes (7)

  • Non-lung Irreversible End-organ Failure

    Day 1 to Day 16

  • Incidence of Adverse Effects (AE)

    Day 1 to Day 16

  • Incidence of Adverse Effects (AE) Requiring Dose-modification

    Day 1 to Day 16

  • +4 more other outcomes

Study Arms (1)

Carfilzomib Treatment Arm

EXPERIMENTAL

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

Interventions

CarfilzomibDRUG

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

Also known as: Kyprolis
Carfilzomib Treatment Arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Interventions

carfilzomib

Results Point of Contact

Title
John McDyer
Organization
University of Pittsburgh
mcdyerjf@upmc.edu
(412) 624-8915

Study Officials

  • John McDyer, MD

    University of Pittsburgh

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Professor of Medicine

Study Record Dates

First Submitted

May 21, 2015

First Posted

June 18, 2015

Study Start

November 1, 2015

Primary Completion

November 9, 2020

Study Completion

July 26, 2021

Last Updated

April 25, 2022

Results First Posted

April 25, 2022

Record last verified: 2022-03

Locations

US(1)