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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
136
AAT is a lyophilized product for intravenous administration
Albumin solution administered intravenously
Stanford University
Stanford, California, United States
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).
Time frame: At Day 28
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.
Time frame: 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.
Time frame: 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.
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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
...and 15 more locations
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At 6 months and 12 months