Back to resultsTreatment of GVHD in Hematopoietic Stem Cell Transplant (HSCT) Recipients Using AAT Plus Corticosteroids (CS) Compared With Corticosteroids Alone (BMT CTN 1705)
Primary Purpose
Graft Versus Host Disease (GVHD)
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Alpha-1 antitrypsin (AAT)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Graft Versus Host Disease (GVHD)
Eligibility Criteria
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
Sites / Locations
- Stanford UniversityRecruiting
- University of FloridaRecruiting
- Moffitt Cancer CenterRecruiting
- Emory UniversityRecruiting
- Northside HospitalRecruiting
- IU HospitalRecruiting
- Univ. of Kansas Cancer CenterRecruiting
- Johns Hopkins HospitalRecruiting
- Dana Farber Cancer InstituteRecruiting
- U-M Medical CenterRecruiting
- Karmanos Cancer CenterRecruiting
- University of MinnesotaRecruiting
- Washington UniversityRecruiting
- MSKCCRecruiting
- Levine Cancer CenterRecruiting
- DukeRecruiting
- Cleveland ClinicRecruiting
- Ohio State Univ.Medical CenterRecruiting
- Vanderbilt-Ingram Cancer CenterRecruiting
- Center for Gene TherapyRecruiting
- MD Anderson Cancer CenterRecruiting
- Virginia Commonwealth Univ.Recruiting
- Fred Hutchinson ClinicRecruiting
- University of WisconsinRecruiting
- Medical College of WisconsinRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AAT
Placebo
Arm Description
Alpha-1 antitrypsin (AAT) is a lyophilized powder for intravenous administration
Albumin solution administered intravenously
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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)
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.
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.
Full Information
NCT ID
NCT04167514
First Posted
November 15, 2019
Last Updated
April 24, 2023
Sponsor
CSL Behring
Collaborators
Blood and Marrow Transplant Clinical Trials Network, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT04167514
Brief Title
Treatment of GVHD in Hematopoietic Stem Cell Transplant (HSCT) Recipients Using AAT Plus Corticosteroids (CS) Compared With Corticosteroids Alone (BMT CTN 1705)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 9, 2020 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
May 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
Collaborators
Blood and Marrow Transplant Clinical Trials Network, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease (GVHD)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
136 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AAT
Arm Type
Experimental
Arm Description
Alpha-1 antitrypsin (AAT) is a lyophilized powder for intravenous administration
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Albumin solution administered intravenously
Intervention Type
Biological
Intervention Name(s)
Alpha-1 antitrypsin (AAT)
Other Intervention Name(s)
Alpha-1 proteinase inhibitor (A1-P1)
Intervention Description
AAT is a lyophilized product for intravenous administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Albumin solution administered intravenously
Primary Outcome Measure Information:
Title
Percent of participants with complete or partial response to acute Graft-versus-Host Disease (GVHD) treatment
Description
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.
Time Frame
28 days post-randomization
Secondary Outcome Measure Information:
Title
Duration of response (DOR)
Description
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.
Time Frame
up to 12 months post-randomization
Title
Percent of participants with non-relapse mortality (NRM)
Description
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.
Time Frame
up to 12 months post-randomization
Title
Percent of participants with overall survival and progression-free survival
Description
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.
Time Frame
up to 12 months post-randomization
Title
Percent of participants with GVHD-free survival
Description
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.
Time Frame
Day 56 post-randomization
Title
Percent of participants with response
Description
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.
Time Frame
At Day 7, 14, 21, 28, 56, and 86 post-randomization
Title
Percent of participants with Grade 2 to 3 systemic infections
Description
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.
Time Frame
up to 30 days after the last dose of study drug
Title
Percent of participants with Grade 3 to 5 treatment-emergent adverse events (TEAEs)
Description
The incidence of Grade 3 to 5 TEAEs (per Common Terminology Criteria for Adverse Events [CTCAE] Version 5.0)
Time Frame
up to 30 days after the last dose of study drug
Title
Percent of participants with chronic GVHD
Description
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.
Time Frame
up to 12 months post-randomization
Title
Percent of participants with disease relapse
Description
The cumulative incidence of relapse/progression of the primary disease, with death prior to relapse/progression treated as a competing risk.
Time Frame
up to 12 months post-randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Registration Coordinator
Phone
610-878-4000
Email
clinicaltrials@cslbehring.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use central contact
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322-1059
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Northside Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
IU Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Univ. of Kansas Cancer Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central; Contact
Facility Name
U-M Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0312
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Karmanos Cancer Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
MSKCC
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Levine Cancer Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Duke
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44124
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Ohio State Univ.Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Center for Gene Therapy
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Virginia Commonwealth Univ.
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Fred Hutchinson Clinic
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.
If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.
IPD Sharing Time Frame
IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.
IPD Sharing Access Criteria
Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.
An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.
The requesting party must execute an appropriate data sharing agreement before IPD will be made available.
Learn more about this trial
Treatment of GVHD in Hematopoietic Stem Cell Transplant (HSCT) Recipients Using AAT Plus Corticosteroids (CS) Compared With Corticosteroids Alone (BMT CTN 1705)
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