Clinical Trials /

The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-Versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant

NCT03805789

Description:

This study is a Phase 2/3 prospective, double-blind, randomized, multi-center, placebo-controlled study for prevention of acute GVHD (aGVHD) in subjects undergoing an allogeneic hematopoietic cell transplant (HCT).

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: The Safety and Efficacy of Alpha-1 Antitrypsin (AAT) for the Prevention of Graft-Versus-host Disease (GVHD) in Patients Receiving Hematopoietic Cell Transplant
  • Official Title: A Phase 2/3, Multicenter, randOmized, Double-blind, Placebo-controlled, stUdy to evaLuate the Safety and Efficacy of Alpha-1 AntiTrypsin for the prEvention of Graft Versus-host Disease in Patients Receiving Hematopoietic Cell Transplant (MODULAATE Study)

Clinical Trial IDs

  • ORG STUDY ID: CSL964_2001
  • SECONDARY ID: 2018-000329-29
  • NCT ID: NCT03805789

Conditions

  • Graft Versus Host Disease

Interventions

DrugSynonymsArms
Alpha-1 antitrypsin (AAT)Alpha-1 proteinase inhibitorAAT (high dose)
PlaceboPlacebo

Purpose

This study is a Phase 2/3 prospective, double-blind, randomized, multi-center, placebo-controlled study for prevention of acute GVHD (aGVHD) in subjects undergoing an allogeneic hematopoietic cell transplant (HCT).

Trial Arms

NameTypeDescriptionInterventions
AAT (low dose)ExperimentalOpen label. Alpha-1 antitrypsin (AAT) is a lyophilized product for intravenous administration
  • Alpha-1 antitrypsin (AAT)
AAT (medium dose)ExperimentalOpen label. AAT is a lyophilized product for intravenous administration
  • Alpha-1 antitrypsin (AAT)
AAT (high dose)ExperimentalOpen label. AAT is a lyophilized product for intravenous administration
  • Alpha-1 antitrypsin (AAT)
AAT (selected dose from open-label)ExperimentalDouble-blind. AAT is a lyophilized product for intravenous administration
  • Alpha-1 antitrypsin (AAT)
PlaceboPlacebo ComparatorAlbumin solution administered intravenously
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female subjects, ≥12 years of age (≥ 18 years of age for subjects at German
             sites only), undergoing HCT for hematological malignancies, including leukemia,
             lymphoma, multiple myeloma, myelodysplastic syndrome and myeloproliferative neoplasms

          -  Planned myeloablative conditioning regimen

        Exclusion Criteria:

          -  Prior autologous or allogeneic HCT

          -  T-cell depleted transplant or planned use of anti-T cell antibody therapy either ex
             vivo or in vivo

          -  Planned umbilical cord blood (UCB) transplant
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The time to Grade II-IV acute graft versus host disease or death
Time Frame:Through 180 days post-hematopoietic cell transplantation (HCT)
Safety Issue:
Description:Acute graft vs host disease (aGVHD) will be assessed using the modified Keystone GVHD scoring system.

Secondary Outcome Measures

Measure:Percent of subjects with Grade II-IV aGVHD or death (acute GVHD Free Survival)
Time Frame:Through 100 days and 180 days post-hematopoietic cell transplant (HCT)
Safety Issue:
Description:
Measure:Percent of subjects with Grade II-IV aGVHD
Time Frame:Within 100 and 180 days post-HCT
Safety Issue:
Description:
Measure:Percent of subjects with Grade III-IV acute GVHD
Time Frame:Within 100 and 180 days post-HCT
Safety Issue:
Description:
Measure:Percent of subjects with Grade II aGVHD
Time Frame:Within 100 and 180 days post-HCT
Safety Issue:
Description:
Measure:Percent of subjects with Grade III aGVHD
Time Frame:Within 100 and 180 days post-HCT
Safety Issue:
Description:
Measure:Percent of subjects with Grade IV aGVHD
Time Frame:Within 100 and 180 days post-HCT
Safety Issue:
Description:
Measure:Number of subjects with all-cause mortality
Time Frame:Within 180 and 365 days post-HCT
Safety Issue:
Description:Death by any cause
Measure:Time to all-cause mortality
Time Frame:Up to 365 days post-HCT
Safety Issue:
Description:Time to death by any cause
Measure:Time to non-relapse mortality
Time Frame:Up to 365 days post-HCT
Safety Issue:
Description:Time to death by any cause other than relapse of primary malignancy
Measure:Percent of subjects with moderate-to-severe chronic GVHD
Time Frame:Within 180 and 365 days post-HCT
Safety Issue:
Description:Moderate-to-severe chronic GVHD graded according to NIH scale
Measure:Percent of subjects with discontinuation of immune suppression therapies
Time Frame:Within 180 and 365 days post-HCT
Safety Issue:
Description:
Measure:Time to neutrophil engraftment
Time Frame:Up to 365 days post-HCT
Safety Issue:
Description:Absolute neutrophil counts ≥ 500/µL
Measure:Time to GVHD relapse-free survival
Time Frame:Up to 365 days post-HCT
Safety Issue:
Description:GVHD free, relapse free, survival defined as time to any of the following events: 1) Grade II-IV acute GVHD, 2) moderate-severe chronic GVHD, 3) primary malignancy relapse or 4) death.
Measure:Percent of subjects with relapse of primary malignancies
Time Frame:Within 180 and 365 days post-HCT
Safety Issue:
Description:
Measure:Percent of subjects with systemic infections
Time Frame:At Days 60, 180, and 365 post-HCT
Safety Issue:
Description:
Measure:Percent of subjects with study drug related adverse events
Time Frame:Up to 365 days post-HCT
Safety Issue:
Description:
Measure:Maximum concentration (Cmax) of AAT
Time Frame:Before and up to 72 after infusion of AAT
Safety Issue:
Description:
Measure:Area under the concentration curve (AUC) for AAT
Time Frame:Before and up to 72 after infusion of AAT
Safety Issue:
Description:
Measure:Clearance (CL) of AAT
Time Frame:Before and up to 72 after infusion of AAT
Safety Issue:
Description:
Measure:Volume of distribution (V) for AAT
Time Frame:Before and up to 72 after infusion of AAT
Safety Issue:
Description:

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:CSL Behring

Last Updated

October 27, 2020