Lung Transplant RejectionPhase 2NCT02474927
Combination Therapy With Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation
A Phase 2 study testing Carfilzomib in people with Lung Transplant Rejection, run by John F. McDyer, MD at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Transplant Rejection
- What is being tested?
- Carfilzomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2015to 26 Jul 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 17Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: 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.
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.
- Conditions
- Lung Transplant Rejection
- Being tested
- Carfilzomib
- Keywords
- antibody-mediated rejection, lung transplant, Carfilzomib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called Kyprolis
Carfilzomib will be used in combination with the conventional therapy (plasma exchange and intravenous immunoglobulins)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Carfilzomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Day 1 to Day 42
Number of Participants With a Decrease in DSA Titer
Number of Participants with a Decrease in DSA Titer.
Measured: 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.
Measured: 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)
Number of Participants with a Decrease in titer of one or more DSA (either reduced MFI or absence of DSA on same dilution).
Measured: Day 1 to Day 90
Number of Participants With a Decrease in DSA Titer
Number of Participants with a Decrease in DSA Titer.
Measured: Day 1 to Day 90
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.
Measured: Day 1 to Day 90
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Absolute change in forced expiratory volume in 1 second (FEV1)
Measured: Day 1 to Day 42
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Measured: Day 1 to Day 90
Presence or Absence of Pathologic Changes Consistent With AMR on Transbronchial Biopsy
Presence or absence of pathologic changes consistent with AMR on transbronchial biopsy
Measured: Day 1 to Day 42
Patient Death Attributable to AMR
Patient death attributable to AMR
Measured: Day 1 to Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2015 (estimated)
- Study start1 Nov 2015
- Primary completion9 Nov 2020
- Study completion26 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lung Transplant RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- John F. McDyer, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, John F. McDyer, MD, University of Pittsburgh
- Investigators
- John McDyer, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02474927
- Sponsor's protocol ID
- PRO15010152
- Status last verified
- Mar 2022
- First submitted
- 21 May 2015
- Last updated
- 25 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Therapy With the Proteasome Inhibitor Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation Trial (PICARD-Lung)
- ClinicalTrials.gov ID
- NCT02474927
- Acronym / sponsor ID
- PRO15010152
- Conditions
- Lung Transplant Rejection
- Keywords
- antibody-mediated rejection, lung transplant, Carfilzomib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- John F. McDyer, MDUniversity, hospital or other
- Study start
- 1 Nov 2015 (actual)
- Primary completion
- 9 Nov 2020 (actual)
- Study completion
- 26 Jul 2021 (actual)
- First posted
- 18 Jun 2015 (estimated)
- Results
- Posted 25 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carfilzomib Treatment Arm | Experimental | Drug: CarfilzomibCarfilzomib 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarfilzomibAlso: KyprolisCarfilzomib will be used in combination with the conventional therapy (plasma exchange and intravenous immunoglobulins) | Drug | Carfilzomib Treatment Arm |
Primary outcome
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
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 DSA Titer
Time frame: Day 1 to Day 42
Number of Participants with a Decrease in DSA Titer.
Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay
Time frame: Day 1 to Day 42
Number of Participants with an Absence of one or more previously positive DSA on Cq1 assay.
7 secondary outcomes
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 DSA Titer
Time frame: Day 1 to Day 90
Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay
Time frame: Day 1 to Day 90
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Day 1 to Day 42
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Day 1 to Day 90
Presence or Absence of Pathologic Changes Consistent With AMR on Transbronchial Biopsy
Time frame: Day 1 to Day 42
Patient Death Attributable to AMR
Time frame: Day 1 to Day 90
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John McDyer, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carfilzomib in people with Lung Transplant Rejection, run by John F. McDyer, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2022.