Treatment of GVHD in Hematopoietic Stem Cell Transplant (HSCT) Recipients Using AAT Plus Corticosteroids (CS) Compared With Corticosteroids Alone
A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase III Trial of Alpha 1 - Antitrypsin (AAT) Combined With Corticosteroids vs Corticosteroids Alone for the Treatment of High Risk Acute Graft-versus-Host Disease (GVHD) Following Allogeneic Hematopoietic Stem Cell Transplant
2 other identifiers
interventional
136
1 country
25
Brief Summary
Study CSL964\_5001 will investigate the efficacy of AAT with corticosteroids compared with corticosteroids alone as first line therapy for patients with high-risk acute GVHD
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Jan 2020
Typical duration for phase_3
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 15, 2019
CompletedFirst Posted
Study publicly available on registry
November 19, 2019
CompletedStudy Start
First participant enrolled
January 9, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 11, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
June 26, 2024
CompletedResults Posted
Study results publicly available
August 29, 2025
CompletedAugust 29, 2025
August 1, 2025
3.7 years
November 15, 2019
June 24, 2025
August 28, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (ORR) to Acute Graft-versus-Host Disease (GVHD) Treatment
The overall response is defined as having a CR or PR at Day 28, along with: being alive, free of any next-line GVHD therapy, and free of escalation of prednisone-equivalent steroid dose to 2.5 milligrams per kilogram (mg/kg)/day or more. The percentage of participants with CR or PR is reported here. Wilson score confidence intervals (CIs) are reported here as a measure of dispersion. The CR was defined as a score of 0 for the GVHD staging in all evaluable organs. The PR was defined as an improvement in one or more organs involved with GVHD symptoms without progression in others. Acute GVHD was graded and assessed for response based on Harris (Mount Sinai Acute GVHD International Consortium \[MAGIC\]) criteria (stage 0, 1, 2, 3, 4) for skin, liver, upper gastrointestinal (GI) tract, and lower GI tract. Participants who had an escalation of prednisone-equivalent steroid dose to 2.5 mg/kg/day or higher were classified as non-responders (NR).
At Day 28
Secondary Outcomes (10)
Duration of Response (DOR)
Up to 12 months
Number of Participants With Non-relapse Mortality (NRM) Event
At 6 and 12 months
Number of Overall and Progression-free Survival Events
At 6 and 12 months
Number of Participants With GVHD-free Survival
At Day 56
Percentage of Participants With Response
At Day 7, 14, 21, 28, 56, and 86
- +5 more secondary outcomes
Other Outcomes (1)
DOR - Supplementary Analysis
Up to 12 months
Study Arms (2)
AAT
EXPERIMENTALAlpha-1 antitrypsin (AAT) is a lyophilized powder for intravenous administration
Placebo
PLACEBO COMPARATORAlbumin solution administered intravenously
Interventions
AAT is a lyophilized product for intravenous administration
Eligibility Criteria
You may qualify if:
- Patients 12 years of age or older
- Initial presentation of acute GVHD after allogeneic hematopoietic cell transplantation for any indication
- Any graft or donor source or conditioning intensity
- Clinical diagnosis of acute GVHD requiring systemic therapy with corticosteroids
You may not qualify if:
- Prior exogenous AAT exposure for GVHD prophylaxis
- Relapsed, progressing, or persistent malignancy
- de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment
- Receiving other drugs for the treatment of GVHD
- Receiving systemic CS for any indication within 7 days before the onset of acute GVHD
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- CSL Behringlead
- Blood and Marrow Transplant Clinical Trials Networkcollaborator
- National Institutes of Health (NIH)collaborator
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- National Cancer Institute (NCI)collaborator
Study Sites (25)
Stanford University
Stanford, California, 94305, United States
University of Florida
Gainesville, Florida, 32608, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University
Atlanta, Georgia, 30322-1059, United States
Northside Hospital
Atlanta, Georgia, 30342, United States
IU Hospital
Indianapolis, Indiana, 46202, United States
Univ. of Kansas Cancer Center
Westwood, Kansas, 66205, United States
Johns Hopkins Hospital
Baltimore, Maryland, 21287, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
U-M Medical Center
Ann Arbor, Michigan, 48109-0312, United States
Karmanos Cancer Center
Detroit, Michigan, 48201, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Washington University
St Louis, Missouri, 63110, United States
MSKCC
New York, New York, 10065, United States
Levine Cancer Center
Charlotte, North Carolina, 28204, United States
Duke
Durham, North Carolina, 27705, United States
Cleveland Clinic
Cleveland, Ohio, 44124, United States
Ohio State Univ.Medical Center
Columbus, Ohio, 43210, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Center for Gene Therapy
Houston, Texas, 77030, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Virginia Commonwealth Univ.
Richmond, Virginia, 23298, United States
Fred Hutchinson Clinic
Seattle, Washington, 98109, United States
University of Wisconsin
Madison, Wisconsin, 53705, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Study Disclosure Manager
- Organization
- CSL Behring
Study Officials
- STUDY DIRECTOR
Study Director
CSL Behring
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 15, 2019
First Posted
November 19, 2019
Study Start
January 9, 2020
Primary Completion
September 11, 2023
Study Completion
June 26, 2024
Last Updated
August 29, 2025
Results First Posted
August 29, 2025
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.
- Access Criteria
- Proposed research should seek to answer a previously unanswered important medical or scientific question. Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD. If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.
CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.