Graft Versus Host Disease (GVHD)Phase 3NCT04167514
Treatment of GVHD in Hematopoietic Stem Cell Transplant (HSCT) Recipients Using AAT Plus Corticosteroids (CS) Compared With Corticosteroids Alone
A Phase 3 study testing Alpha-1 antitrypsin (AAT) in people with Graft Versus Host Disease (GVHD), run by CSL Behring at 25 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Graft Versus Host Disease (GVHD)
- What is being tested?
- Alpha-1 antitrypsin (AAT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 136 participants
- Where
- 25 sitesUnited States
- Study dates
- 9 Jan 2020to 26 Jun 2024
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
U-M Medical Center
Ann Arbor, Michigan, 48109-0312
Emory University
Atlanta, Georgia, 30322-1059
Northside Hospital
Atlanta, Georgia, 30342
Johns Hopkins Hospital
Baltimore, Maryland, 21287
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Levine Cancer Center
Charlotte, North Carolina, 28204
Cleveland Clinic
Cleveland, Ohio, 44124
Ohio State Univ.Medical Center
Columbus, Ohio, 43210
Karmanos Cancer Center
Detroit, Michigan, 48201
Duke
Durham, North Carolina, 27705
University of Florida
Gainesville, Florida, 32608
Center for Gene Therapy
Houston, Texas, 77030
MD Anderson Cancer Center
Houston, Texas, 77030
IU Hospital
Indianapolis, Indiana, 46202
University of Wisconsin
Madison, Wisconsin, 53705
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
MSKCC
New York, New York, 10065
Virginia Commonwealth Univ.
Richmond, Virginia, 23298
Fred Hutchinson Clinic
Seattle, Washington, 98109
Washington University
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
Moffitt Cancer Center
Tampa, Florida, 33612
Univ. of Kansas Cancer Center
Westwood, Kansas, 66205
About this study
Official title: 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
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
- Conditions
- Graft Versus Host Disease (GVHD)
- Being tested
- Alpha-1 antitrypsin (AAT), Placebo
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha-1 antitrypsin (AAT)Biological
Also called Alpha-1 proteinase inhibitor (A1-P1)
AAT is a lyophilized product for intravenous administration
PlaceboDrug
Albumin solution administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| AAT | Experimental | Alpha-1 antitrypsin (AAT) is a lyophilized powder for intravenous administration Receives: Biological: Alpha-1 antitrypsin (AAT) |
| Placebo | Placebo comparator | Albumin solution administered intravenously Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: At Day 28
Secondary outcomes (10)
Duration of Response (DOR)
The DOR was defined as time from the Day 28 response (CR or PR) until the first of the following events occurs: progression of acute GVHD, death, any next-line GVHD therapy, or escalation of prednisone-equivalent steroids to greater than or equal to (>=) 2.5 mg/kg/day. Wald CIs are reported here as a measure of dispersion.
Measured: Up to 12 months
Number of Participants With Non-relapse Mortality (NRM) Event
An event of NRM was death without prior evidence of relapse/progression of the primary disease, where relapse/progression was treated as a competing risk. Cumulative incidence of NRM at 6 and 12 months post-randomization is reported here for this outcome measure.
Measured: At 6 and 12 months
Number of Overall and Progression-free Survival Events
An event for overall survival (OS) was death from any cause, while an event for progression-free survival (PFS) was death from any cause or relapse/progression of the primary disease.
Measured: At 6 and 12 months
Number of Participants With GVHD-free Survival
GVHD-free survival was defined as participants being alive, free of acute or chronic GVHD, and free of any next-line GVHD therapy or escalation of steroids to >=2.5 mg/kg/day prednisone or equivalent for treatment of GVHD.
Measured: At Day 56
Percentage of Participants With Response
The percentage of participants with CR, PR (including subset with very good partial response [VGPR]), and treatment failure (TF). The designation of TF consisted of participants with NR, mixed response (MR) or progression. The initiation of additional systemic (next-line) GVHD therapies, escalation of prednisone equivalent steroid dose to >= 2.5 mg/kg/day, or death from any cause prior to the assessment timepoint was also considered a TF. Simultaneous Goodman CIs are provided for category proportions for each arm at each assessment time.
Measured: At Day 7, 14, 21, 28, 56, and 86
Percentage of Participants With Response Allowing for Approved Next-line Therapy
The percentage of participants with CR, PR (including subset with VGPR), and TF allowing for treatment with next-line therapy. The designation of TF consisted of participants with NR, MR, or progression. The escalation of prednisone-equivalent steroid dose to >= 2.5 mg/kg/day or death from any cause prior to the assessment timepoint was also considered a TF. Simultaneous Goodman CIs are provided for category proportions for each arm at each assessment time.
Measured: At Day 7, 14, 21, 28, 56, and 86
Incidence of Grade 2 to 3 Systemic Infections
The cumulative incidence of Grade 2 to 3 systemic infections. Grade 2 to 3 systemic infections were defined according to the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Manual of Procedures.
Measured: Up to 90 days (including 30 days after last dose of study drug)
Percentage of Participants With Grade 3 to 5 Treatment-emergent Adverse Events (TEAEs)
The incidence of Grade 3 to 5 TEAEs (per Common Terminology Criteria for Adverse Events [CTCAE] Version 5.0). Wilson score CIs are reported here as a measure of dispersion.
Measured: Up to 30 days after the last dose of study drug
Cumulative Incidence of Chronic GVHD
Chronic GVHD was defined per National Institutes of Health (NIH) Consensus Criteria. Diagnosis of chronic GVHD of any severity (mild, moderate, or severe) was considered an event for this outcome measure, where death before cGVHD was treated as a competing risk.
Measured: At 6 and 12 months
Cumulative Incidence of Disease Relapse/ Progression of Primary Disease
The cumulative incidence of relapse/progression of the primary disease, with death prior to relapse/progression treated as a competing risk. Death without prior relapse/progression was treated as a competing risk for relapse/progression.
Measured: At 6 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2019
- Study start9 Jan 2020
- Primary completion11 Sep 2023
- Study completion26 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graft Versus Host Disease (GVHD)Studies of the same condition, open and under way.
- More trials run by CSL BehringThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 136 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Blood and Marrow Transplant Clinical Trials Network, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04167514
- Sponsor's protocol ID
- CSL964_5001 / BMT CTN 1705
- Other IDs
- BMT CTN Protocol 1705
- Status last verified
- Jun 2026
- First submitted
- 15 Nov 2019
- Last updated
- 28 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.