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Trial record 1 of 1 for:    csl964_5001
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Treatment of GVHD in Hematopoietic Stem Cell Transplant (HSCT) Recipients Using AAT Plus Corticosteroids (CS) Compared With Corticosteroids Alone

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04167514
Recruitment Status : Recruiting
First Posted : November 19, 2019
Last Update Posted : October 22, 2020
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Graft Versus Host Disease (GVHD) Biological: Alpha-1 antitrypsin (AAT) Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 122 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : January 9, 2020
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : November 2023


Arm Intervention/treatment
Experimental: AAT
Alpha-1 antitrypsin (AAT) is a lyophilized powder for intravenous administration
Biological: Alpha-1 antitrypsin (AAT)
AAT is a lyophilized product for intravenous administration
Other Name: Alpha-1 proteinase inhibitor (A1-P1)

Placebo Comparator: Placebo
Albumin solution administered intravenously
Drug: Placebo
Albumin solution administered intravenously




Primary Outcome Measures :
  1. Percent of participants with complete or partial response to acute Graft-versus-Host Disease (GVHD) treatment [ Time Frame: 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 :
  1. Duration of response (DOR) [ Time Frame: 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.

  2. Percent of participants with non-relapse mortality (NRM) [ Time Frame: 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.

  3. Percent of participants with overall survival and progression-free survival [ Time Frame: 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.

  4. Percent of participants with GVHD-free survival [ Time Frame: 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.

  5. Percent of participants with response [ Time Frame: 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.

  6. Percent of participants with Grade 2 to 3 systemic infections [ Time Frame: 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.

  7. Percent of participants with Grade 3 to 5 treatment-emergent adverse events (TEAEs) [ Time Frame: 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)

  8. Percent of participants with chronic GVHD [ Time Frame: 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.

  9. Percent of participants with disease relapse [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients 18 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04167514


Contacts
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Contact: Trial Registration Coordinator 610-878-4000 clinicaltrials@cslbehring.com

Locations
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United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32608
Contact: Use Central Contact         
United States, Georgia
Northside Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Use Central Contact         
United States, Indiana
IU Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Use Central Contact         
United States, Kansas
Univ. of Kansas Cancer Center Recruiting
Westwood, Kansas, United States, 66205
Contact: Use Central Contact         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Use Central; Contact         
United States, Michigan
U-M Medical Center Recruiting
Ann Arbor, Michigan, United States, 48109-0312
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United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
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United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
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United States, North Carolina
Levine Cancer Center Recruiting
Charlotte, North Carolina, United States, 28204
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Duke Recruiting
Durham, North Carolina, United States, 27705
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United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44124
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United States, Texas
Center for Gene Therapy Recruiting
Houston, Texas, United States, 77030
Contact: Use Central Contact         
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
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United States, Washington
Fred Hutchinson Clinic Recruiting
Seattle, Washington, United States, 98109
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United States, Wisconsin
University of Wisconsin Recruiting
Madison, Wisconsin, United States, 53705
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Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
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Sponsors and Collaborators
CSL Behring
Blood and Marrow Transplant Clinical Trials Network
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Investigators
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Study Director: Study Director CSL Behring
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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT04167514    
Other Study ID Numbers: CSL964_5001 / BMT CTN 1705
First Posted: November 19, 2019    Key Record Dates
Last Update Posted: October 22, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.
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.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Protease Inhibitors
Alpha 1-Antitrypsin
Protein C Inhibitor
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypsin Inhibitors
Serine Proteinase Inhibitors