- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03459040
A Proof of Concept Pilot Trial of Alpha-1-Antitrypsin for Pre-Emption Of Steroid-Refractory Acute GVHD
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Duarte, California, United States, 91010
- City of Hope
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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New York
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New York, New York, United States, 10029
- Icahn School of Medicine at Mount Sinai
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Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- High risk prediction score as determined by the Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm at either day 7 or day 14 post Hematopoietic cell transplant (HCT).
- Any donor type (e.g., related, unrelated) or stem cell source (bone marrow, peripheral blood, cord blood).
- Donor and recipient match each other for at least 7/8 HLA-loci (HLA-A, B, C, and DR)
- Any conditioning regimen (non-myeloablative, myeloablative, or reduced intensity) is acceptable.
- GVHD prophylaxis must include a calcineurin inhibitor combined with methotrexate or mycophenolate.
- The use of serotherapy to prevent GVHD (e.g., antithymocyte globulin) prior to day 3 post-HCT is permitted
- Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert syndrome within 3 days prior to enrollment.
- ALT/SGPT and AST/SGOT must be <5 x the upper limit of the normal range within 3 days prior to enrollment.
- Signed and dated written informed consent obtained from patient or legal representative.
Exclusion Criteria:
- Patients who develop acute GVHD prior to start of study drug
- Patients at very high risk for relapse post HCT as defined by very high disease risk index
- Patients participating in a clinical trial where prevention of GVHD is the primary endpoint
- Uncontrolled active infection (i.e., progressive symptoms related to infection despite treatment or persistently positive microbiological cultures despite treatment or any other evidence of severe sepsis)
- Patients who are pregnant
- Patients on dialysis within 7 days of enrollment
- Patients requiring ventilator support or oxygen supplementation exceeding 40% FiO2 within 14 days of enrollment.
- Patients receiving investigational agent within 30 days of enrollment. However, the Principal Investigator (PI) may approve prior use of an investigational agent if the agent is not expected to interfere with the safety or the efficacy of alpha-1-antitrypsin.
- History of allergic reaction to alpha-1-antitrypsin
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: alpha-1-antitrypsin (AAT)
16 doses of AAT through a catheter placed into a blood vessel over eight weeks.
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AAT will be given either in the hospital or the outpatient clinic two times per week.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of High Risk Patients Who Develop Steroid Refractory GVHD
Time Frame: Day 100 post HCT.
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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.
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Day 100 post HCT.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Alive at 6 Months and 1 Year
Time Frame: 6 months and 1 year
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Overall survival - The number of that patients are still alive from the start of treatment at 6 months and 1 year
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6 months and 1 year
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Number of Participants With Non-relapse Mortality (NRM)
Time Frame: 6 months and 1 year
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Number of participants with NRM - deaths which could not be attributed to disease relapse or progression.
Non-relapse mortality defined as death without prior relapse.
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6 months and 1 year
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Number of Participants With Relapse
Time Frame: 1 year
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Number of participants with relapse at one year.
Relapse defined as recurrence of disease that required transplant.
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1 year
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Number of Participants With Clinically Relevant GVHD States Grade II-IV GVHD
Time Frame: 100 days
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Number of participants with clinically relevant GVHD states grade II-IV GVHD requiring systemic treatment. GVHD grades II-IV are defined as
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100 days
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Number of Participants Achieving Overall Response
Time Frame: Day 28
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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.
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Day 28
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Number of Participants With Severe GI GVHD Stage 3 or 4
Time Frame: By day 100 post-HCT
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Number 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.
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By day 100 post-HCT
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Number of Participants With Chronic GVHD Requiring Systemic Steroid Treatment
Time Frame: 1 year
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Number 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.
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1 year
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Number of Participants With Serious Infections
Time Frame: 1 year
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Number 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.
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1 year
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: John Levine, MD, Icahn School of Medicine at Mount Sinai
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Respiratory Tract Diseases
- Immune System Diseases
- Lung Diseases
- Liver Diseases
- Genetic Diseases, Inborn
- Subcutaneous Emphysema
- Emphysema
- Alpha 1-Antitrypsin Deficiency
- Graft vs Host Disease
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protease Inhibitors
- Serine Proteinase Inhibitors
- Trypsin Inhibitors
- Alpha 1-Antitrypsin
- Protein C Inhibitor
Other Study ID Numbers
- GCO 17-2666
- P01CA039542 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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