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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carfilzomib | Drug | Carfilzomib will be used in combination with the conventional therapy (plasma exchange and intravenous immunoglobulins) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 90 |
| Number of Participants With a Decrease in DSA Titer |
| Measure | Description | Time Frame |
|---|---|---|
| Non-lung Irreversible End-organ Failure | Non-lung irreversible end-organ failure | Day 1 to Day 16 |
| Incidence of Adverse Effects (AE) | Incidence of adverse effects (AE) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John McDyer, MD | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | 15213 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Carfilzomib: Carfilzomib will be used in combination with the conventional therapy (plasma exchange and intravenous immunoglobulins) |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Carfilzomib: Carfilzomib will be used in combination with the conventional therapy (plasma exchange and intravenous immunoglobulins) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Decrease in titer of one or more DSA (either reduced MFI or absence of DSA on same dilution) | Posted | Count of Participants | Participants | Day 1 to Day 42 |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Carfilzomib: Carfilzomib will be used in combination with the conventional therapy (plasma exchange and intravenous immunoglobulins) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Posterior reversible encephalopathy syndrome | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John McDyer | University of Pittsburgh | (412) 624-8915 | mcdyerjf@upmc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 20, 2018 | May 25, 2021 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 19, 2020 | May 25, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| C524865 | carfilzomib |
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|
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 | 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) | 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) | Absolute Change in Forced Expiratory Volume in 1 Second (FEV1) | 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 | Day 1 to Day 42 |
| Patient Death Attributable to AMR | Patient death attributable to AMR | Day 1 to Day 90 |
| Day 1 to Day 16 |
| Incidence of Adverse Effects (AE) Requiring Dose-modification | Incidence of adverse effects (AE) requiring dose-modification | Day 1 to Day 16 |
| Incidence of Hypogammaglobulinemia | Incidence of hypogammaglobulinemia | Day 1 to Day 16 |
| Incidence of Culture-proven de Novo Infection | Incidence of culture-proven de novo infection | Day 1 to Day 42 |
| Diagnosis of Systemic Inflammatory Response Syndrome | Diagnosis of systemic inflammatory response syndrome | Day 1 to Day 16 |
| Patient Death | Patient death | Day 1 to Day 90 |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Number of Participants With a Decrease in DSA Titer | Number of Participants with a Decrease in DSA Titer. | Change in DSA Titer (Titer Decreased) [6 not evaluable] | Posted | Count of Participants | Participants | Day 1 to Day 42 |
|
|
|
| Primary | 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. | Absence of one or more previously positive DSA on Cq1 assay [14 not evaluable] | Posted | Count of Participants | Participants | Day 1 to Day 42 |
|
|
|
| Secondary | 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). | Decrease in titer of one or more DSA (either reduced MFI or absence of DSA on same dilution)[2 not evaluable] | Posted | Count of Participants | Participants | Day 1 to Day 90 |
|
|
|
| Secondary | Number of Participants With a Decrease in DSA Titer | Number of Participants with a Decrease in DSA Titer. | Change in DSA Titer (Titer Decreased) [9 not evaluable] | Posted | Count of Participants | Participants | Day 1 to Day 90 |
|
|
|
| Secondary | 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. | Absence of one or more previously positive DSA on Cq1 assay [12 not evaluable] | Posted | Count of Participants | Participants | Day 1 to Day 90 |
|
|
|
| Secondary | Absolute Change in Forced Expiratory Volume in 1 Second (FEV1) | Absolute change in forced expiratory volume in 1 second (FEV1) | Posted | Median | Full Range | FEV1% | Day 1 to Day 42 |
|
|
|
|
| Secondary | Absolute Change in Forced Expiratory Volume in 1 Second (FEV1) | Absolute Change in Forced Expiratory Volume in 1 Second (FEV1) | Posted | Median | Full Range | Median FEV1 value | Day 1 to Day 90 |
|
|
|
|
| Secondary | Presence or Absence of Pathologic Changes Consistent With AMR on Transbronchial Biopsy | Presence or absence of pathologic changes consistent with AMR on transbronchial biopsy | Unable to calculate at dates specified at this time. Re-biopsy of patients is not routinely completed. Research biopsy was not part of the protocol. | Posted | Day 1 to Day 42 |
|
|
| Secondary | Patient Death Attributable to AMR | Patient death attributable to AMR | Posted | Count of Participants | Participants | Day 1 to Day 90 |
|
|
|
| Other Pre-specified | Non-lung Irreversible End-organ Failure | Non-lung irreversible end-organ failure | Posted | Count of Participants | Participants | Day 1 to Day 16 |
|
|
|
| Other Pre-specified | Incidence of Adverse Effects (AE) | Incidence of adverse effects (AE) | Incidence of adverse effects (AE) | Posted | Count of Participants | Participants | Day 1 to Day 16 |
|
|
|
| Other Pre-specified | Incidence of Adverse Effects (AE) Requiring Dose-modification | Incidence of adverse effects (AE) requiring dose-modification | Posted | Count of Participants | Participants | Day 1 to Day 16 |
|
|
|
| Other Pre-specified | Incidence of Hypogammaglobulinemia | Incidence of hypogammaglobulinemia | Posted | Count of Participants | Participants | Day 1 to Day 16 |
|
|
|
| Other Pre-specified | Incidence of Culture-proven de Novo Infection | Incidence of culture-proven de novo infection | Posted | Count of Participants | Participants | Day 1 to Day 42 |
|
|
|
| Other Pre-specified | Diagnosis of Systemic Inflammatory Response Syndrome | Diagnosis of systemic inflammatory response syndrome | Posted | Count of Participants | Participants | Day 1 to Day 16 |
|
|
|
| Other Pre-specified | Patient Death | Patient death | Posted | Count of Participants | Participants | Day 1 to Day 90 |
|
|
|
| 3 |
| 22 |
| 4 |
| 22 |
| 22 |
| 22 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Nervous system disorders - Other (Brain Herniation) | Nervous system disorders | MedDRA 10.0 | Systematic Assessment | brain herniation |
|
| diverticulitis with perforation | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| thombotic microangiopathy with acute renal failure | Renal and urinary disorders | MedDRA 10.0 | Systematic Assessment |
|
| Sepsis | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment | Sepsis |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA 10.0 | Systematic Assessment |
|
| Bloating | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Confusion | Psychiatric disorders | MedDRA 10.0 | Systematic Assessment |
|
| Edema limbs | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment | Erythema |
|
| General disorders and administration site conditions - Other, specify | General disorders | MedDRA 10.0 | Systematic Assessment | Facial Tingling |
|
| Fatigue | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Hemolysis | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | MedDRA 10.0 | Systematic Assessment |
|
| INR increased | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 10.0 | Systematic Assessment |
|
| White blood cell decreased | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 10.0 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment | Pneumonia |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Pulmonary edema | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
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