Trial Outcomes & Findings for A Pilot Study of Alpha-1-Antitrypsin (AAT) in Steroid Refractory Acute Graft vs Host Disease (NCT NCT01700036)
NCT ID: NCT01700036
Last Updated: 2018-11-27
Results Overview
To estimate the proportion of patients with steroid refractory acute Graft vs Host Disease) GvHD who respond (achieve either PR or CR) to Alpha-1 Antitrypsin (AAT) at a dose of 60mg/kg twice weekly for 8 doses Partial Response (PR) is defined as a decrease of at least one grade in the severity of GVHD without deterioration of any organ systems by d28 of therapy. Complete Response (CR) is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
40 participants
Primary outcome timeframe
4 weeks
Results posted on
2018-11-27
Participant Flow
Participant milestones
| Measure |
Treatment Arm
Alpha-1-Antitrypsin (AAT) for the treatment of Steroid Refractory Acute Graft vs Host Disease.
Alpha-1-Antitrypsin (AAT): AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28. A second course of treatment will not be given.
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|---|---|
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Overall Study
STARTED
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40
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Overall Study
COMPLETED
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40
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Pilot Study of Alpha-1-Antitrypsin (AAT) in Steroid Refractory Acute Graft vs Host Disease
Baseline characteristics by cohort
| Measure |
Treatment Arm
n=40 Participants
Alpha-1-Antitrypsin (AAT) for the treatment of Steroid Refractory Acute Graft vs Host Disease.
Alpha-1-Antitrypsin (AAT): AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28. A second course of treatment will not be given.
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|---|---|
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Age, Continuous
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59 years
n=5 Participants
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Sex: Female, Male
Female
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13 Participants
n=5 Participants
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Sex: Female, Male
Male
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27 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: 4 weeksTo estimate the proportion of patients with steroid refractory acute Graft vs Host Disease) GvHD who respond (achieve either PR or CR) to Alpha-1 Antitrypsin (AAT) at a dose of 60mg/kg twice weekly for 8 doses Partial Response (PR) is defined as a decrease of at least one grade in the severity of GVHD without deterioration of any organ systems by d28 of therapy. Complete Response (CR) is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.
Outcome measures
| Measure |
Treatment Arm
n=40 Participants
Alpha-1-Antitrypsin (AAT): AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28.
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|---|---|
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Percentage of Patients That Respond to Treatment
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65 percentage of patients
Interval 48.0 to 79.0
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SECONDARY outcome
Timeframe: 4 weeksTo estimate the proportion of patients in complete remission without additional therapy at four weeks after the last dose of AAT Complete remission is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.
Outcome measures
| Measure |
Treatment Arm
n=40 Participants
Alpha-1-Antitrypsin (AAT): AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28.
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|---|---|
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Percentage of Patients Who Achieve a Complete Response to Treatment
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35 percentage of patients
Interval 21.0 to 52.0
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SECONDARY outcome
Timeframe: 30 daysTo estimate the incidence of infection during and following treatment of steroid refractory acute GVHD with AAT
Outcome measures
| Measure |
Treatment Arm
n=40 Participants
Alpha-1-Antitrypsin (AAT): AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28.
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|---|---|
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Percentage of Patients With Documented Infection
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32.5 percentage of patients
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SECONDARY outcome
Timeframe: 6 monthsPopulation: 40 patients were enrolled and 26 patients achieved a CR or PR.
Survival at 6 months in patients receiving AAT treatment for steroid refractory acute GVHD for patients that achieved a CR or PR. Partial Response (PR) is defined as a decrease of at least one grade in the severity of GVHD without deterioration of any organ systems by d28 of therapy. Complete Response (CR) is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.
Outcome measures
| Measure |
Treatment Arm
n=26 Participants
Alpha-1-Antitrypsin (AAT): AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28.
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|---|---|
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The Percentage of Patients Alive at 6 Months for Patients in CR or PR
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50 percentage of patients
Interval 34.0 to 73.0
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SECONDARY outcome
Timeframe: Baseline, 2 weeks, and 4 weeksThe fold change in levels of plasma biomarkers IL-6, TNF-alpha and ST2 will be measured pre-treatment and after the administration of AAT treatment for steroid refractory GvHD.
Outcome measures
| Measure |
Treatment Arm
n=40 Participants
Alpha-1-Antitrypsin (AAT): AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28.
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|---|---|
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Mean Fold Change in Plasma Biomarkers
IL-6 Fold Change at 2 weeks
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6.3 fold change from baseline
Standard Error 3.6
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Mean Fold Change in Plasma Biomarkers
IL-6 Fold Change at 4 weeks
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4 fold change from baseline
Standard Error 1.9
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Mean Fold Change in Plasma Biomarkers
TNF-alpha Fold Change at 2 weeks
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1.7 fold change from baseline
Standard Error 0.8
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Mean Fold Change in Plasma Biomarkers
TNF-alpha Fold Change at 4 weeks
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1.1 fold change from baseline
Standard Error 0.2
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Mean Fold Change in Plasma Biomarkers
ST2 Fold Change at 2 weeks
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1.2 fold change from baseline
Standard Error 0.4
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Mean Fold Change in Plasma Biomarkers
ST2 Fold Change at 4 weeks
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1.5 fold change from baseline
Standard Error 0.7
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SECONDARY outcome
Timeframe: 4 weeksPlasma levels of Alpha-1-Antitrypsin(AAT)will be measured.
Outcome measures
| Measure |
Treatment Arm
n=40 Participants
Alpha-1-Antitrypsin (AAT): AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28.
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|---|---|
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Mean Plasma Levels for Alpha-1-Antitrypsin (AAT)
AAT levels at two weeks
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196.8 mg/dl
Standard Error 11.91
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Mean Plasma Levels for Alpha-1-Antitrypsin (AAT)
AAT levels at 4 weeks
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214.8 mg/dl
Standard Error 18.62
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Adverse Events
Treatment Arm
Serious events: 11 serious events
Other events: 31 other events
Deaths: 8 deaths
Serious adverse events
| Measure |
Treatment Arm
n=40 participants at risk
Alpha-1-Antitrypsin (AAT): AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28.
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|---|---|
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Blood and lymphatic system disorders
Disseminated intravascular coagulation
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Gastrointestinal disorders
Colitis
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Gastrointestinal disorders
Lower gastrointestinal hemorrhage
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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General disorders
Multi-organ failure
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Immune system disorders
Immune system disorder
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5.0%
2/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Bladder infection
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Hepatic infection
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Infection
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Sepsis
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5.0%
2/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Investigations
Blood bilirubin increased
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Respiratory, thoracic and mediastinal disorders
Hypoxia
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Respiratory, thoracic and mediastinal disorders
Respiratory failure
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7.5%
3/40 • Number of events 4 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Other adverse events
| Measure |
Treatment Arm
n=40 participants at risk
Alpha-1-Antitrypsin (AAT): AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28.
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|---|---|
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Blood and lymphatic system disorders
Anemia
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10.0%
4/40 • Number of events 4 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Blood and lymphatic system disorders
Disseminated intravascular coagulation
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
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7.5%
3/40 • Number of events 3 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Cardiac disorders
Atrial fibrillation
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Cardiac disorders
Sinus bradycardia
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Cardiac disorders
Sinus tachycardia
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Cardiac disorders
Supraventricular tachycardia
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Gastrointestinal disorders
Abdominal pain
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Gastrointestinal disorders
Ascites
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Gastrointestinal disorders
Colitis
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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|
Gastrointestinal disorders
Diarrhea
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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|
Gastrointestinal disorders
Gastrointestinal disorder
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Gastrointestinal disorders
Lower gastrointestinal hemorrhage
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7.5%
3/40 • Number of events 3 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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General disorders
Fever
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5.0%
2/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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General disorders
Multi-organ failure
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Immune system disorders
Immune system disorder
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5.0%
2/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Bladder infection
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Device related infection
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Enterocolitis infectious
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Hepatic infection
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Infection
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27.5%
11/40 • Number of events 16 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Kidney infection
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2.5%
1/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Lung infection
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Mucosal infection
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Sepsis
|
7.5%
3/40 • Number of events 3 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Skin infection
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5.0%
2/40 • Number of events 3 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Infections and infestations
Urinary tract infection
|
7.5%
3/40 • Number of events 3 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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|
Injury, poisoning and procedural complications
Spinal fracture
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5.0%
2/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Investigations
Alanine aminotransferase increased
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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Investigations
Blood bilirubin increased
|
15.0%
6/40 • Number of events 6 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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|
Investigations
Lymphocyte count decreased
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12.5%
5/40 • Number of events 6 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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|
Investigations
Lymphocyte count increased
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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|
Investigations
Neutrophil count decreased
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2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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|
Investigations
Platelet count decreased
|
12.5%
5/40 • Number of events 7 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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|
Investigations
White blood cell decreased
|
7.5%
3/40 • Number of events 3 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
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|
Metabolism and nutrition disorders
Anorexia
|
2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
17.5%
7/40 • Number of events 7 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
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Metabolism and nutrition disorders
Hypoalbuminemia
|
7.5%
3/40 • Number of events 3 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified
|
2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Nervous system disorders
Encephalopathy
|
2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Nervous system disorders
Nervous system disorder
|
2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Psychiatric disorders
Delirium
|
5.0%
2/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Renal and urinary disorders
Acute kidney injury
|
2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Renal and urinary disorders
Hematuria
|
2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Renal and urinary disorders
Urinary retention
|
2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.0%
2/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
10.0%
4/40 • Number of events 4 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
5.0%
2/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
7.5%
3/40 • Number of events 4 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
5.0%
2/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Vascular disorders
Hypertension
|
5.0%
2/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Vascular disorders
Hypotension
|
2.5%
1/40 • Number of events 1 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
|
Vascular disorders
Thromboembolic event
|
5.0%
2/40 • Number of events 2 • Patients will be followed for adverse events for 30 days after the last dose of the study drug.
|
Additional Information
Dr. Pavan Reddy, MD
University of Michigan Cancer Center
Phone: 734-936-8785
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place