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CompletedNCT02474927Updated Apr 25, 2022Results posted

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

A Phase 2 interventional study of Carfilzomib in Lung Transplant Rejection, sponsored by John F. McDyer, MD. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-04-25.

Sponsored by John F. McDyer, MD · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
22
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Lung Transplant Rejection

Keywords

  • antibody-mediated rejection
  • lung transplant
  • Carfilzomib
03

In context

Lead sponsor

This is the only study on the registry with John F. McDyer, MD as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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)
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
22 participants (actual)

Study arms

  • 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

Interventions

  • DrugCarfilzomib

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

    Also known as: Kyprolis

06

What researchers measure

Primary outcomes

  1. 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).

    Time frame: Day 1 to Day 42

  2. Number of Participants With a Decrease in DSA Titer

    Number of Participants with a Decrease in DSA Titer.

    Time frame: Day 1 to Day 42

  3. 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.

    Time frame: Day 1 to Day 42

Secondary outcomes

  1. 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).

    Time frame: Day 1 to Day 90

  2. Number of Participants With a Decrease in DSA Titer

    Number of Participants with a Decrease in DSA Titer.

    Time frame: Day 1 to Day 90

  3. 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.

    Time frame: Day 1 to Day 90

  4. Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)

    Absolute change in forced expiratory volume in 1 second (FEV1)

    Time frame: Day 1 to Day 42

  5. Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)

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

    Time frame: Day 1 to Day 90

  6. Presence or Absence of Pathologic Changes Consistent With AMR on Transbronchial Biopsy

    Presence or absence of pathologic changes consistent with AMR on transbronchial biopsy

    Time frame: Day 1 to Day 42

  7. Patient Death Attributable to AMR

    Patient death attributable to AMR

    Time frame: Day 1 to Day 90

Other outcomes

  1. Non-lung Irreversible End-organ Failure

    Non-lung irreversible end-organ failure

    Time frame: Day 1 to Day 16

  2. Incidence of Adverse Effects (AE)

    Incidence of adverse effects (AE)

    Time frame: Day 1 to Day 16

  3. Incidence of Adverse Effects (AE) Requiring Dose-modification

    Incidence of adverse effects (AE) requiring dose-modification

    Time frame: Day 1 to Day 16

  4. Incidence of Hypogammaglobulinemia

    Incidence of hypogammaglobulinemia

    Time frame: Day 1 to Day 16

  5. Incidence of Culture-proven de Novo Infection

    Incidence of culture-proven de novo infection

    Time frame: Day 1 to Day 42

  6. Diagnosis of Systemic Inflammatory Response Syndrome

    Diagnosis of systemic inflammatory response syndrome

    Time frame: Day 1 to Day 16

  7. Patient Death

    Patient death

    Time frame: Day 1 to Day 90

07

Results

Posted Apr 25, 2022

Participant flow

Participant flow — Overall Study
MilestoneCarfilzomib Treatment Arm
Started22
Completed22
Not completed0

Outcome measures

PrimaryNumber 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).

Time frame:
Day 1 to Day 42
Reported as:
Count of participants · Participants
Number of Participants With a Decrease in Titer of One or More DSA (Either Reduced MFI or Absence of DSA on Same Dilution)
ParticipantsCarfilzomib Treatment Arm
Number of Participants With a Decrease in Titer of One or More DSA (Either Reduced MFI or Absence of DSA on Same Dilution)17
PrimaryNumber of Participants With a Decrease in DSA Titer

Number of Participants with a Decrease in DSA Titer.

Time frame:
Day 1 to Day 42
Reported as:
Count of participants · Participants
Number of Participants With a Decrease in DSA Titer
ParticipantsCarfilzomib Treatment Arm
Number of Participants With a Decrease in DSA Titer13
PrimaryNumber 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.

Time frame:
Day 1 to Day 42
Reported as:
Count of participants · Participants
Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay
ParticipantsCarfilzomib Treatment Arm
Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay5
SecondaryNumber 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).

Time frame:
Day 1 to Day 90
Reported as:
Count of participants · Participants
Number of Participants With a Decrease in Titer of One or More DSA (Either Reduced MFI or Absence of DSA on Same Dilution)
ParticipantsCarfilzomib Treatment Arm
Number of Participants With a Decrease in Titer of One or More DSA (Either Reduced MFI or Absence of DSA on Same Dilution)17
SecondaryNumber of Participants With a Decrease in DSA Titer

Number of Participants with a Decrease in DSA Titer.

Time frame:
Day 1 to Day 90
Reported as:
Count of participants · Participants
Number of Participants With a Decrease in DSA Titer
ParticipantsCarfilzomib Treatment Arm
Number of Participants With a Decrease in DSA Titer10
SecondaryNumber 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.

Time frame:
Day 1 to Day 90
Reported as:
Count of participants · Participants
Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay
ParticipantsCarfilzomib Treatment Arm
Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay6
SecondaryAbsolute Change in Forced Expiratory Volume in 1 Second (FEV1)

Absolute change in forced expiratory volume in 1 second (FEV1)

Time frame:
Day 1 to Day 42
Reported as:
Median · FEV1%
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
FEV1%Carfilzomib Treatment Arm
Baseline1.77 (0.80 to 2.83)
Day 421.93 (1.06 to 3.22)
Statistical analysis
  • Carfilzomib Treatment Arm · Wilcoxon Signed Rank · p = 0.36
SecondaryAbsolute Change in Forced Expiratory Volume in 1 Second (FEV1)

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

Time frame:
Day 1 to Day 90
Reported as:
Median · Median FEV1 value
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Median FEV1 valueCarfilzomib Treatment Arm
Baseline1.77 (0.80 to 2.83)
Day 902.09 (0.71 to 3.65)
Statistical analysis
  • Carfilzomib Treatment Arm · Wilcoxon Signed Rank · p = 0.16
SecondaryPresence or Absence of Pathologic Changes Consistent With AMR on Transbronchial Biopsy

Presence or absence of pathologic changes consistent with AMR on transbronchial biopsy

Time frame:
Day 1 to Day 42

No measurements were reported for this outcome.

SecondaryPatient Death Attributable to AMR

Patient death attributable to AMR

Time frame:
Day 1 to Day 90
Reported as:
Count of participants · Participants
Patient Death Attributable to AMR
ParticipantsCarfilzomib Treatment Arm
Patient Death Attributable to AMR1
Other pre-specifiedNon-lung Irreversible End-organ Failure

Non-lung irreversible end-organ failure

Time frame:
Day 1 to Day 16
Reported as:
Count of participants · Participants
Non-lung Irreversible End-organ Failure
ParticipantsCarfilzomib Treatment Arm
Non-lung Irreversible End-organ Failure1
Other pre-specifiedIncidence of Adverse Effects (AE)

Incidence of adverse effects (AE)

Time frame:
Day 1 to Day 16
Reported as:
Count of participants · Participants
Incidence of Adverse Effects (AE)
ParticipantsCarfilzomib Treatment Arm
Incidence of Adverse Effects (AE)22
Other pre-specifiedIncidence of Adverse Effects (AE) Requiring Dose-modification

Incidence of adverse effects (AE) requiring dose-modification

Time frame:
Day 1 to Day 16
Reported as:
Count of participants · Participants
Incidence of Adverse Effects (AE) Requiring Dose-modification
ParticipantsCarfilzomib Treatment Arm
Incidence of Adverse Effects (AE) Requiring Dose-modification5
Other pre-specifiedIncidence of Hypogammaglobulinemia

Incidence of hypogammaglobulinemia

Time frame:
Day 1 to Day 16
Reported as:
Count of participants · Participants
Incidence of Hypogammaglobulinemia
ParticipantsCarfilzomib Treatment Arm
Incidence of Hypogammaglobulinemia0
Other pre-specifiedIncidence of Culture-proven de Novo Infection

Incidence of culture-proven de novo infection

Time frame:
Day 1 to Day 42
Reported as:
Count of participants · Participants
Incidence of Culture-proven de Novo Infection
ParticipantsCarfilzomib Treatment Arm
Incidence of Culture-proven de Novo Infection6
Other pre-specifiedDiagnosis of Systemic Inflammatory Response Syndrome

Diagnosis of systemic inflammatory response syndrome

Time frame:
Day 1 to Day 16
Reported as:
Count of participants · Participants
Diagnosis of Systemic Inflammatory Response Syndrome
ParticipantsCarfilzomib Treatment Arm
Diagnosis of Systemic Inflammatory Response Syndrome0
Other pre-specifiedPatient Death

Patient death

Time frame:
Day 1 to Day 90
Reported as:
Count of participants · Participants
Patient Death
ParticipantsCarfilzomib Treatment Arm
Patient Death3

Adverse events

Collected over 1 year. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Carfilzomib Treatment Arm3/22 (13.6%)4/22 (18.2%)22/22 (100%)
Most frequent serious events
Most frequent serious events
EventCarfilzomib Treatment Arm
Posterior reversible encephalopathy syndromeNervous system disorders1/22
Respiratory failureRespiratory, thoracic and mediastinal disorders1/22
Nervous system disorders - Other (Brain Herniation)Nervous system disorders1/22
diverticulitis with perforationGastrointestinal disorders1/22
thombotic microangiopathy with acute renal failureRenal and urinary disorders1/22
SepsisBlood and lymphatic system disorders1/22
Most frequent other events
Showing 10 of 27
Most frequent other events
EventCarfilzomib Treatment Arm
Acute kidney injuryRenal and urinary disorders15/22
AnemiaBlood and lymphatic system disorders12/22
White blood cell decreasedInvestigations12/22
Lymphocyte count decreasedInvestigations12/22
Platelet count decreasedInvestigations9/22
Edema limbsGeneral disorders6/22
HyperkalemiaMetabolism and nutrition disorders4/22
NauseaGastrointestinal disorders4/22
DiarrheaGastrointestinal disorders3/22
Neutrophil count decreasedInvestigations3/22

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Carfilzomib Treatment Arm
<=18 years0
Between 18 and 65 years16
>=65 years6
Age, Continuous
Age, Continuous(years)Carfilzomib Treatment Arm
Mean48 (21 to 72)
Sex: Female, Male
Sex: Female, Male(Participants)Carfilzomib Treatment Arm
Female7
Male15
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Carfilzomib Treatment Arm
Hispanic or Latino0
Not Hispanic or Latino22
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Carfilzomib Treatment Arm
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American5
White17
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Carfilzomib Treatment Arm
United States22
08

Study locations

1 site
  • University of Pittsburgh Medical Center
    Pittsburgh, Pennsylvania 15213, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Sep 20, 2018
  • Informed consent form · Mar 19, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 25, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02474927
Lead sponsor
John F. McDyer, MD
Responsible party
John F. McDyer, MD (Associate Professor of Medicine, University of Pittsburgh) — Sponsor-investigator
First posted
Jun 18, 2015
Start date
Nov 1, 2015
Primary completion
Nov 9, 2020
Completion
Jul 26, 2021
Results posted
Apr 25, 2022
Last update
Apr 25, 2022

Study contacts

John McDyer, MD
principal investigator · University of Pittsburgh

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.

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