Treatment of GVHD in Hematopoietic Stem Cell Transplant (HSCT) Recipients Using AAT Plus Corticosteroids (CS) Compared With Corticosteroids Alone
- 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
- COMPLETED
- 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 Overall Response Rate (ORR) to Acute Graft-versus-Host Disease (GVHD) Treatment At Day 28 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).
- Secondary Outcome Measures
Name Time Method Number of Participants With GVHD-free Survival At Day 56 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.
Incidence of Grade 2 to 3 Systemic Infections Up to 90 days (including 30 days after last dose of study drug) 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.
Cumulative Incidence of Disease Relapse/ Progression of Primary Disease At 6 months and 12 months 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.
Percentage 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). Wilson score CIs are reported here as a measure of dispersion.
Cumulative Incidence of Chronic GVHD At 6 and 12 months 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.
Duration of Response (DOR) Up to 12 months 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.
Number of Participants With Non-relapse Mortality (NRM) Event At 6 and 12 months 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.
Number of Overall and Progression-free Survival Events At 6 and 12 months 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.
Percentage of Participants With Response At Day 7, 14, 21, 28, 56, and 86 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.
Percentage of Participants With Response Allowing for Approved Next-line Therapy At Day 7, 14, 21, 28, 56, and 86 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.
Trial Locations
- Locations (25)
Stanford University
🇺🇸Stanford, California, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
IU Hospital
🇺🇸Indianapolis, Indiana, United States
Univ. of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
U-M Medical Center
🇺🇸Ann Arbor, Michigan, United States
Scroll for more (15 remaining)Stanford University🇺🇸Stanford, California, United States