Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    csl964_5001
Previous Study | Return to List | Next Study

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 : August 10, 2021
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

Tracking Information
First Submitted Date  ICMJE November 15, 2019
First Posted Date  ICMJE November 19, 2019
Last Update Posted Date August 10, 2021
Actual Study Start Date  ICMJE January 9, 2020
Estimated Primary Completion Date November 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2019)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment of GVHD in Hematopoietic Stem Cell Transplant (HSCT) Recipients Using AAT Plus Corticosteroids (CS) Compared With Corticosteroids Alone
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Graft Versus Host Disease (GVHD)
Intervention  ICMJE
  • Biological: Alpha-1 antitrypsin (AAT)
    AAT is a lyophilized product for intravenous administration
    Other Name: Alpha-1 proteinase inhibitor (A1-P1)
  • Drug: Placebo
    Albumin solution administered intravenously
Study Arms  ICMJE
  • Experimental: AAT
    Alpha-1 antitrypsin (AAT) is a lyophilized powder for intravenous administration
    Intervention: Biological: Alpha-1 antitrypsin (AAT)
  • Placebo Comparator: Placebo
    Albumin solution administered intravenously
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 15, 2019)
122
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2023
Estimated Primary Completion Date November 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Registration Coordinator 610-878-4000 clinicaltrials@cslbehring.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04167514
Other Study ID Numbers  ICMJE CSL964_5001 / BMT CTN 1705
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: 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.

Responsible Party CSL Behring
Study Sponsor  ICMJE CSL Behring
Collaborators  ICMJE
  • Blood and Marrow Transplant Clinical Trials Network
  • National Institutes of Health (NIH)
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Cancer Institute (NCI)
Investigators  ICMJE
Study Director: Study Director CSL Behring
PRS Account CSL Behring
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP