Trial Outcomes & Findings for Combination Therapy With Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation (NCT NCT02474927)
NCT ID: NCT02474927
Last Updated: 2022-04-25
Results Overview
Number of Participants with a Decrease in titer of one or more DSA (either reduced MFI or absence of DSA on same dilution).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
22 participants
Primary outcome timeframe
Day 1 to Day 42
Results posted on
2022-04-25
Participant Flow
Participant milestones
| Measure |
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)
|
|---|---|
|
Overall Study
STARTED
|
22
|
|
Overall Study
COMPLETED
|
22
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Combination Therapy With Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation
Baseline characteristics by cohort
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=99 Participants
|
|
Age, Continuous
|
48 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
22 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 42Population: 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).
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Number of Participants With a Decrease in Titer of One or More DSA (Either Reduced MFI or Absence of DSA on Same Dilution)
|
17 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 42Population: Change in DSA Titer (Titer Decreased) \[6 not evaluable\]
Number of Participants with a Decrease in DSA Titer.
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=16 Participants
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)
|
|---|---|
|
Number of Participants With a Decrease in DSA Titer
|
13 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 42Population: Absence of one or more previously positive DSA on Cq1 assay \[14 not evaluable\]
Number of Participants with an Absence of one or more previously positive DSA on Cq1 assay.
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=8 Participants
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)
|
|---|---|
|
Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay
|
5 Participants
|
SECONDARY outcome
Timeframe: Day 1 to Day 90Population: Decrease in titer of one or more DSA (either reduced MFI or absence of DSA on same dilution)\[2 not evaluable\]
Number of Participants with a Decrease in titer of one or more DSA (either reduced MFI or absence of DSA on same dilution).
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=20 Participants
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)
|
|---|---|
|
Number of Participants With a Decrease in Titer of One or More DSA (Either Reduced MFI or Absence of DSA on Same Dilution)
|
17 Participants
|
SECONDARY outcome
Timeframe: Day 1 to Day 90Population: Change in DSA Titer (Titer Decreased) \[9 not evaluable\]
Number of Participants with a Decrease in DSA Titer.
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=13 Participants
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)
|
|---|---|
|
Number of Participants With a Decrease in DSA Titer
|
10 Participants
|
SECONDARY outcome
Timeframe: Day 1 to Day 90Population: Absence of one or more previously positive DSA on Cq1 assay \[12 not evaluable\]
Number of Participants with an Absence of one or more previously positive DSA on Cq1 assay.
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=10 Participants
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)
|
|---|---|
|
Number of Participants With an Absence of One or More Previously Positive DSA on Cq1 Assay
|
6 Participants
|
SECONDARY outcome
Timeframe: Day 1 to Day 42Absolute change in forced expiratory volume in 1 second (FEV1)
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Baseline
|
1.77 FEV1%
Interval 0.8 to 2.83
|
|
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Day 42
|
1.93 FEV1%
Interval 1.06 to 3.22
|
SECONDARY outcome
Timeframe: Day 1 to Day 90Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Baseline
|
1.77 Median FEV1 value
Interval 0.8 to 2.83
|
|
Absolute Change in Forced Expiratory Volume in 1 Second (FEV1)
Day 90
|
2.09 Median FEV1 value
Interval 0.71 to 3.65
|
SECONDARY outcome
Timeframe: Day 1 to Day 42Population: 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.
Presence or absence of pathologic changes consistent with AMR on transbronchial biopsy
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 to Day 90Patient death attributable to AMR
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Patient Death Attributable to AMR
|
1 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 to Day 16Non-lung irreversible end-organ failure
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Non-lung Irreversible End-organ Failure
|
1 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 to Day 16Population: Incidence of adverse effects (AE)
Incidence of adverse effects (AE)
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Incidence of Adverse Effects (AE)
|
22 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 to Day 16Incidence of adverse effects (AE) requiring dose-modification
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Incidence of Adverse Effects (AE) Requiring Dose-modification
|
5 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 to Day 16Incidence of hypogammaglobulinemia
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Incidence of Hypogammaglobulinemia
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 to Day 42Incidence of culture-proven de novo infection
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Incidence of Culture-proven de Novo Infection
|
6 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 to Day 16Diagnosis of systemic inflammatory response syndrome
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Diagnosis of Systemic Inflammatory Response Syndrome
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 to Day 90Patient death
Outcome measures
| Measure |
Carfilzomib Treatment Arm
n=22 Participants
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)
|
|---|---|
|
Patient Death
|
3 Participants
|
Adverse Events
Carfilzomib Treatment Arm
Serious events: 4 serious events
Other events: 22 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Carfilzomib Treatment Arm
n=22 participants at risk
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)
|
|---|---|
|
Nervous system disorders
Posterior reversible encephalopathy syndrome
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Nervous system disorders
Nervous system disorders - Other (Brain Herniation)
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
diverticulitis with perforation
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Renal and urinary disorders
thombotic microangiopathy with acute renal failure
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Blood and lymphatic system disorders
Sepsis
|
4.5%
1/22 • Number of events 1 • 1 year
|
Other adverse events
| Measure |
Carfilzomib Treatment Arm
n=22 participants at risk
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)
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
54.5%
12/22 • Number of events 18 • 1 year
|
|
Renal and urinary disorders
Acute kidney injury
|
68.2%
15/22 • Number of events 24 • 1 year
|
|
Gastrointestinal disorders
Bloating
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Investigations
Alanine aminotransferase increased
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Investigations
Aspartate aminotransferase increased
|
4.5%
1/22 • Number of events 2 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
13.6%
3/22 • Number of events 3 • 1 year
|
|
Psychiatric disorders
Confusion
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
General disorders
Edema limbs
|
27.3%
6/22 • Number of events 7 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
General disorders
General disorders and administration site conditions - Other, specify
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
General disorders
Fatigue
|
9.1%
2/22 • Number of events 2 • 1 year
|
|
Nervous system disorders
Headache
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Blood and lymphatic system disorders
Hemolysis
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
18.2%
4/22 • Number of events 10 • 1 year
|
|
Investigations
INR increased
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Blood and lymphatic system disorders
Leukocytosis
|
9.1%
2/22 • Number of events 2 • 1 year
|
|
Investigations
White blood cell decreased
|
54.5%
12/22 • Number of events 22 • 1 year
|
|
Investigations
Lymphocyte count decreased
|
54.5%
12/22 • Number of events 22 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
18.2%
4/22 • Number of events 8 • 1 year
|
|
Investigations
Neutrophil count decreased
|
13.6%
3/22 • Number of events 4 • 1 year
|
|
Investigations
Platelet count decreased
|
40.9%
9/22 • Number of events 13 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
4.5%
1/22 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
9.1%
2/22 • Number of events 2 • 1 year
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
4.5%
1/22 • Number of events 2 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place