Trial Outcomes & Findings for A Proof of Concept Pilot Trial of Alpha-1-Antitrypsin for Pre-Emption Of Steroid-Refractory Acute GVHD (NCT NCT03459040)
NCT ID: NCT03459040
Last Updated: 2021-07-12
Results Overview
Number of High Risk patients who develop steroid refractory GVHD by day 100 post Hematopoietic cell transplant (HCT) . Steroid refractory GVHD defined as patients who did not achieve Complete Response (CR) or Partial Response (PR) by day 28 of systemic steroid treatment OR if additional immunosuppression beyond steroids was given for treatment of GVHD prior to 28 days of steroid treatment. * CR: All evaluable organs (skin, liver, GI tract) stage 0. For a response to be scored as CR on day 28, the patient must be in CR on that day and have had no intervening additional GVHD therapy. * PR: An improvement in one or more organ involved with GVHD symptoms without worsening in others. For a response to be scored as PR on day 28, the patient must be in PR on that day and have had no intervening additional GVHD therapy.
COMPLETED
PHASE2
30 participants
Day 100 post HCT.
2021-07-12
Participant Flow
Subjects were recruited and enrolled between August 2018 and July 2019.
Participant milestones
| Measure |
Alpha-1-antitrypsin (AAT)
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Overall Study
STARTED
|
30
|
|
Overall Study
COMPLETED
|
21
|
|
Overall Study
NOT COMPLETED
|
9
|
Reasons for withdrawal
| Measure |
Alpha-1-antitrypsin (AAT)
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Overall Study
Death
|
8
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Proof of Concept Pilot Trial of Alpha-1-Antitrypsin for Pre-Emption Of Steroid-Refractory Acute GVHD
Baseline characteristics by cohort
| Measure |
Alpha-1-antitrypsin (AAT)
n=30 Participants
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Age, Continuous
|
51 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
26 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Diagnosis
Myelodysplastic syndrome
|
13 Participants
n=93 Participants
|
|
Diagnosis
Acute myelogenous leukemia
|
9 Participants
n=93 Participants
|
|
Diagnosis
Acute lymphoblastic leukemia
|
5 Participants
n=93 Participants
|
|
Diagnosis
Nonmalignant disease
|
2 Participants
n=93 Participants
|
|
Diagnosis
Non-Hodgkin's lymphoma
|
1 Participants
n=93 Participants
|
|
Donor
Matched related
|
3 Participants
n=93 Participants
|
|
Donor
Matched unrelated
|
26 Participants
n=93 Participants
|
|
Donor
Mismatched related
|
0 Participants
n=93 Participants
|
|
Donor
Mismatched unrelated
|
1 Participants
n=93 Participants
|
|
GVHD Prophylaxis
CNI/MTX - calcineurin inhibitor/methotrexate
|
14 Participants
n=93 Participants
|
|
GVHD Prophylaxis
CNI/MMF -Calcineurin inhibitors/mycophenolate mofetil
|
0 Participants
n=93 Participants
|
|
GVHD Prophylaxis
calcineurin inhibitor/sirolimus
|
15 Participants
n=93 Participants
|
|
GVHD Prophylaxis
Cyclophosphamide based
|
0 Participants
n=93 Participants
|
|
GVHD Prophylaxis
Other
|
1 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Day 100 post HCT.Number of High Risk patients who develop steroid refractory GVHD by day 100 post Hematopoietic cell transplant (HCT) . Steroid refractory GVHD defined as patients who did not achieve Complete Response (CR) or Partial Response (PR) by day 28 of systemic steroid treatment OR if additional immunosuppression beyond steroids was given for treatment of GVHD prior to 28 days of steroid treatment. * CR: All evaluable organs (skin, liver, GI tract) stage 0. For a response to be scored as CR on day 28, the patient must be in CR on that day and have had no intervening additional GVHD therapy. * PR: An improvement in one or more organ involved with GVHD symptoms without worsening in others. For a response to be scored as PR on day 28, the patient must be in PR on that day and have had no intervening additional GVHD therapy.
Outcome measures
| Measure |
Alpha-1-antitrypsin (AAT)
n=30 Participants
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Number of High Risk Patients Who Develop Steroid Refractory GVHD
|
6 Participants
|
SECONDARY outcome
Timeframe: 6 months and 1 yearOverall survival - The number of that patients are still alive from the start of treatment at 6 months and 1 year
Outcome measures
| Measure |
Alpha-1-antitrypsin (AAT)
n=30 Participants
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Number of Participants Alive at 6 Months and 1 Year
6 months
|
26 Participants
|
|
Number of Participants Alive at 6 Months and 1 Year
1 year
|
22 Participants
|
SECONDARY outcome
Timeframe: 6 months and 1 yearNumber of participants with NRM - deaths which could not be attributed to disease relapse or progression. Non-relapse mortality defined as death without prior relapse.
Outcome measures
| Measure |
Alpha-1-antitrypsin (AAT)
n=30 Participants
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Number of Participants With Non-relapse Mortality (NRM)
6 months
|
3 Participants
|
|
Number of Participants With Non-relapse Mortality (NRM)
1 year
|
6 Participants
|
SECONDARY outcome
Timeframe: 1 yearNumber of participants with relapse at one year. Relapse defined as recurrence of disease that required transplant.
Outcome measures
| Measure |
Alpha-1-antitrypsin (AAT)
n=30 Participants
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Number of Participants With Relapse
|
3 Participants
|
SECONDARY outcome
Timeframe: 100 daysNumber of participants with clinically relevant GVHD states grade II-IV GVHD requiring systemic treatment. GVHD grades II-IV are defined as * Rash covering more than 50% of the body surface area, AND/OR * Total bilirubin \> 2 mg/dl AND/OR * Persistent nausea or vomiting, AND/OR * Diarrhea \> 500 ml/day AND/OR * Severe abdominal pain requiring treatment or blood present in the diarrhea
Outcome measures
| Measure |
Alpha-1-antitrypsin (AAT)
n=30 Participants
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Number of Participants With Clinically Relevant GVHD States Grade II-IV GVHD
|
12 Participants
|
SECONDARY outcome
Timeframe: Day 28Population: This is the number of patients who developed GVHD and were systemically treated (not all patients on study developed GVHD and of those that did develop GVHD, not all received systemic treatment).
For patients who develop GVHD prior to day 100 post-HCT, the number of participants achieving overall response. The overall response rate = complete remission and partial remission (CR + PR) 28 days after initiation of systemic steroid treatment.
Outcome measures
| Measure |
Alpha-1-antitrypsin (AAT)
n=16 Participants
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Number of Participants Achieving Overall Response
|
10 Participants
|
SECONDARY outcome
Timeframe: By day 100 post-HCTNumber of participants with severe GI GVHD stage 3 or 4. GI GVHD stage 3 or 4 is defined as diarrhea \>1000 ml/day OR severe abdominal pain requiring treatment OR blood present in the diarrhea.
Outcome measures
| Measure |
Alpha-1-antitrypsin (AAT)
n=30 Participants
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Number of Participants With Severe GI GVHD Stage 3 or 4
|
4 Participants
|
SECONDARY outcome
Timeframe: 1 yearNumber of participants with chronic GVHD requiring systemic steroid treatment. Chronic GVHD Requiring Systemic Steroid Treatment: defined as the development of symptoms of chronic GVHD according to NIH Consensus Criteria that require treatment with oral or intravenous corticosteroids.
Outcome measures
| Measure |
Alpha-1-antitrypsin (AAT)
n=30 Participants
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Number of Participants With Chronic GVHD Requiring Systemic Steroid Treatment
|
8 Participants
|
SECONDARY outcome
Timeframe: 1 yearNumber of participants with serious infections (defined as grade 3 by the Blood and Marrow Transplant Clinical Trials Network). Serious Infection: Defined as bacterial, fungal, viral or parasitic infections that required oral or intravenous treatments such as antibiotics.
Outcome measures
| Measure |
Alpha-1-antitrypsin (AAT)
n=30 Participants
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Number of Participants With Serious Infections
|
2 Participants
|
Adverse Events
Alpha-1-antitrypsin (AAT)
Serious adverse events
| Measure |
Alpha-1-antitrypsin (AAT)
n=30 participants at risk
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
General disorders
Engraftment Syndrome
|
3.3%
1/30 • up to 1 year
|
|
Immune system disorders
GVHD
|
13.3%
4/30 • up to 1 year
|
|
Nervous system disorders
Headache
|
3.3%
1/30 • up to 1 year
|
|
Infections and infestations
Line Infection: Gram negative Bacilli-Citrobacter
|
3.3%
1/30 • up to 1 year
|
|
Infections and infestations
Pneumonia
|
3.3%
1/30 • Number of events 1 • up to 1 year
|
|
Infections and infestations
Fungal Infection: Pneumocystis carinii pneumonia (PCP)
|
3.3%
1/30 • up to 1 year
|
|
Infections and infestations
Fungal Infection: Aspergillus
|
3.3%
1/30 • up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage (DAH)
|
6.7%
2/30 • up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
6.7%
2/30 • up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Edema
|
6.7%
2/30 • up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome
|
3.3%
1/30 • up to 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Relapse
|
6.7%
2/30 • up to 1 year
|
|
Blood and lymphatic system disorders
Thrombotic microangiopathy
|
3.3%
1/30 • up to 1 year
|
Other adverse events
| Measure |
Alpha-1-antitrypsin (AAT)
n=30 participants at risk
AAT was administered intravenously at a loading dose of 90 mg/kg (study day 0), followed by twice weekly doses of 45 mg/kg for 15 more doses (totaling 16 doses over 8 weeks).
|
|---|---|
|
Cardiac disorders
Atrial Fibrillation
|
3.3%
1/30 • up to 1 year
|
|
Skin and subcutaneous tissue disorders
Maculopapular rash with engraftment syndrome
|
3.3%
1/30 • up to 1 year
|
|
Gastrointestinal disorders
Oral mucositis
|
3.3%
1/30 • up to 1 year
|
|
Skin and subcutaneous tissue disorders
Maculopapular Rash
|
3.3%
1/30 • up to 1 year
|
|
Cardiac disorders
Hypertension
|
3.3%
1/30 • up to 1 year
|
|
Infections and infestations
Klebsiella
|
3.3%
1/30 • up to 1 year
|
|
Injury, poisoning and procedural complications
Infusion Reaction
|
16.7%
5/30 • up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
3.3%
1/30 • up to 1 year
|
|
General disorders
Generalized muscle weakness
|
3.3%
1/30 • up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Edema
|
3.3%
1/30 • up to 1 year
|
|
Blood and lymphatic system disorders
Anemia
|
3.3%
1/30 • up to 1 year
|
|
Blood and lymphatic system disorders
Hyponatremia
|
3.3%
1/30 • up to 1 year
|
|
Blood and lymphatic system disorders
Hyperglycemia
|
3.3%
1/30 • up to 1 year
|
|
Blood and lymphatic system disorders
Low platelets
|
3.3%
1/30 • up to 1 year
|
Additional Information
Dr. John Levine
Icahn School of Medicine at Mount Sinai
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place