Treatment of GVHD in Hematopoietic Stem Cell Transplant (HSCT) Recipients Using AAT Plus Corticosteroids (CS) Compared With Corticosteroids Alone (BMT CTN 1705)
- Conditions
- Graft Versus Host Disease (GVHD)
- Interventions
- Biological: Alpha-1 antitrypsin (AAT)Drug: Placebo
- Registration Number
- NCT04167514
- Lead Sponsor
- CSL Behring
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 136
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AAT Alpha-1 antitrypsin (AAT) Alpha-1 antitrypsin (AAT) is a lyophilized powder for intravenous administration Placebo Placebo Albumin solution administered intravenously
- Primary Outcome Measures
Name Time Method Percent of participants with complete or partial response to acute Graft-versus-Host Disease (GVHD) treatment 28 days post-randomization Acute GVHD will be graded and assessed for response based on Harris criteria (stage 0, 1, 2, 3, 4) for skin, liver, upper gastrointestinal (GI) tract, and lower GI tract. Complete response (CR) is defined as a score of 0 for the GVHD staging in all evaluable organs.
Partial response (PR) is defined as improvement in one or more organs involved with GVHD symptoms without progression in others.
- Secondary Outcome Measures
Name Time Method Percent of participants with overall survival and progression-free survival up to 12 months post-randomization An event for overall survival is death from any cause, while an event for progression-free survival is death from any cause or relapse/progression of the primary disease.
Percent of participants with GVHD-free survival Day 56 post-randomization Patients alive, free of active acute or chronic GVHD, and without other systemic agents or escalation of steroids added for treatment of GVHD will be considered successes for this endpoint.
Duration of response (DOR) up to 12 months post-randomization DOR is defined as time from the Day 28 response (CR or PR) to any of the following events: relapse/progression of acute GVHD, new systemic salvage therapy for acute GVHD, re-escalation of steroids to greater or equal to 2.5 mg/kg prednisone or equivalent, or death from any cause.
Percent of participants with non-relapse mortality (NRM) up to 12 months post-randomization An event of NRM is death without prior evidence of relapse/progression of the primary disease, where relapse/progression is treated as a competing risk.
Percent of participants with Grade 2 to 3 systemic infections up to 30 days after the last dose of study drug The incidence of Grade 2 to 3 systemic infections. Grade 2 to 3 systemic infections will be defined according to BMT CTN Manual of Procedures.
Percent of participants with chronic GVHD up to 12 months post-randomization Chronic GVHD is defined per National Institutes of Health (NIH) Consensus Criteria. Diagnosis of chronic GVHD of any severity (mild, moderate, or severe) is considered an event for this endpoint.
Percent of participants with response At Day 7, 14, 21, 28, 56, and 86 post-randomization The proportion of patients with CR, PR (including subset with VGPR), and treatment failure (TF). The designation of TF will consist of patients with no response (NR), mixed response (MR), progression or initiation of additional systemic (second-line) GVHD therapies or escalation of steroids. Death from any cause will also be considered a TF.
Percent of participants with Grade 3 to 5 treatment-emergent adverse events (TEAEs) up to 30 days after the last dose of study drug The incidence of Grade 3 to 5 TEAEs (per Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0)
Percent of participants with disease relapse up to 12 months post-randomization The cumulative incidence of relapse/progression of the primary disease, with death prior to relapse/progression treated as a competing risk.
Trial Locations
- Locations (25)
Univ. of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Ohio State Univ.Medical Center
🇺🇸Columbus, Ohio, United States
Center for Gene Therapy
🇺🇸Houston, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Duke
🇺🇸Durham, North Carolina, United States
Stanford University
🇺🇸Stanford, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
MSKCC
🇺🇸New York, New York, United States
Levine Cancer Center
🇺🇸Charlotte, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Fred Hutchinson Clinic
🇺🇸Seattle, Washington, United States
Virginia Commonwealth Univ.
🇺🇸Richmond, Virginia, United States
IU Hospital
🇺🇸Indianapolis, Indiana, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Karmanos Cancer Center
🇺🇸Detroit, Michigan, United States
U-M Medical Center
🇺🇸Ann Arbor, Michigan, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Florida
🇺🇸Gainesville, Florida, United States