Treatment of GVHD in Hematopoietic Stem Cell Transplant (HSCT) Recipients Using AAT Plus Corticosteroids (CS) Compared With Corticosteroids Alone (BMT CTN 1705)

Graft Versus Host Disease (GVHD) Clinical Trial

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 (BMT CTN 1705)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04167514
• Other study ID #: CSL964_5001 / BMT CTN 1705
• Secondary ID: BMT CTN Protocol
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 9, 2020
• Est. completion date: May 2024

Study information

• Verified date: February 2024
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 136
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Graft Versus Host Disease (GVHD)
• Graft vs Host Disease

Intervention

Biological:
• Alpha-1 antitrypsin (AAT)
AAT is a lyophilized product for intravenous administration

Drug:
• Placebo
Albumin solution administered intravenously

Locations

Country	Name	City	State
United States	U-M Medical Center	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Levine Cancer Center	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	Ohio State Univ.Medical Center	Columbus	Ohio
United States	Karmanos Cancer Center	Detroit	Michigan
United States	Duke	Durham	North Carolina
United States	University of Florida	Gainesville	Florida
United States	Center for Gene Therapy	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	IU Hospital	Indianapolis	Indiana
United States	University of Wisconsin	Madison	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	MSKCC	New York	New York
United States	Virginia Commonwealth Univ.	Richmond	Virginia
United States	Washington University	Saint Louis	Missouri
United States	Fred Hutchinson Clinic	Seattle	Washington
United States	Stanford University	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida
United States	Univ. of Kansas Cancer Center	Westwood	Kansas

Sponsors (5)

Lead Sponsor	Collaborator
CSL Behring	Blood and Marrow Transplant Clinical Trials Network, National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of participants with complete or partial response to acute Graft-versus-Host Disease (GVHD) treatment	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.	28 days post-randomization
Secondary	Duration of response (DOR)	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.	up to 12 months post-randomization
Secondary	Percent of participants with non-relapse mortality (NRM)	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.	up to 12 months post-randomization
Secondary	Percent of participants with overall survival and progression-free survival	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.	up to 12 months post-randomization
Secondary	Percent of participants with GVHD-free survival	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.	Day 56 post-randomization
Secondary	Percent of participants with response	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.	At Day 7, 14, 21, 28, 56, and 86 post-randomization
Secondary	Percent of participants with Grade 2 to 3 systemic infections	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.	up to 30 days after the last dose of study drug
Secondary	Percent 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)	up to 30 days after the last dose of study drug
Secondary	Percent of participants with chronic GVHD	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.	up to 12 months post-randomization
Secondary	Percent of participants with disease relapse	The cumulative incidence of relapse/progression of the primary disease, with death prior to relapse/progression treated as a competing risk.	up to 12 months post-randomization