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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

Other trials in United States

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

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 groups in NCT04167514
Study groupRoleWhat they receive
AATExperimentalAlpha-1 antitrypsin (AAT) is a lyophilized powder for intravenous administration
Receives: Biological: Alpha-1 antitrypsin (AAT)
PlaceboPlacebo comparatorAlbumin solution administered intravenously
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: At Day 28

Secondary outcomes (10)

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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)

  8. 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

  9. 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

  10. 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.

  1. First posted19 Nov 2019
  2. Study start9 Jan 2020
  3. Primary completion11 Sep 2023
  4. Study completion26 Jun 2024

Resources

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)
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
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.

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) to Acute Graft-versus-Host Disease (GVHD) Treatment (time frame: At Day 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04167514.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2026.

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