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

Primary Purpose

Acute-graft-versus-host Disease

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Alpha-1 antitrypsin (AAT)
Placebo
Sponsored by
CSL Behring
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute-graft-versus-host Disease

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 (ie, anti-thymocyte globulin [ATG], alemtuzumab) for GVHD prophylaxis
  • Planned umbilical cord blood (UCB) transplant

Sites / Locations

  • Scottsdale HH Cancer TransplantRecruiting
  • Emory UniversityRecruiting
  • University of Kansas Cancer CenterRecruiting
  • University of MichiganRecruiting
  • Duke University Medical CenterRecruiting
  • Cleveland Cancer Center (University Hospitals UH - Seidman Cancer Center Ireland Cancer Center)Recruiting
  • Centennial Medical Center (TriStar BMT)Recruiting
  • The University of Texas-MD Anderson Cancer CenterRecruiting
  • Methodist HospitalRecruiting
  • Primary Children's HospitalRecruiting
  • Seattle Cancer Care AllianceRecruiting
  • Royal Brisbane and Women's HospitalRecruiting
  • University EssenRecruiting
  • Uniklinik Köln, lnnere MedizRecruiting
  • Complejo Hospitalario de NavarraRecruiting
  • Hospital Universitario Vall d'Recruiting
  • Hospital Regional Universitario de MalagaRecruiting
  • Universitario de SalamancaRecruiting
  • Hospital Universitario MarquésRecruiting
  • The Christie NHS FoundationRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

AAT (low dose)

AAT (medium dose)

AAT (high dose)

AAT (selected dose from open-label)

Placebo

Arm Description

Open label. Alpha-1 antitrypsin (AAT) is a lyophilized product for intravenous administration

Open label. AAT is a lyophilized product for intravenous administration

Open label. AAT is a lyophilized product for intravenous administration

Double-blind. AAT is a lyophilized product for intravenous administration

Albumin solution administered intravenously

Outcomes

Primary Outcome Measures

The time to Grade II-IV acute graft versus host disease (aGVHD) or death
Acute graft vs host disease (aGVHD) will be assessed using the modified Keystone GVHD scoring system.

Secondary Outcome Measures

Proportion of subjects with lower GI aGVHD or Grade III-IV aGVHD in any organ
Proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3
Proportion of subjects with Grade II-IV aGVHD or death
Proportion of subjects with lower GI aGVHD
Proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3
Number of deaths (relapse and nonrelapse-related)
Death by any cause
Proportion of subjects with Grade III-IV aGVHD or death
Proportion of subjects with moderate-to-severe chronic GVHD
Moderate-to-severe chronic GVHD graded according to NIH scale
Proportion of subjects who have discontinued immune suppression therapies including standard- of- care GVHD prophylaxis and steroid treatment
Time to neutrophil engraftment
Time to the first of 3 consecutive days of absolute neutrophil counts ≥ 500/µL
Time to GVHD relapse-free survival
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.
Proportion of subjects with relapse of primary malignancies
Proportion of subjects with Grade II-IV aGVHD with an overall (complete + partial) response, complete response and partial response
Percent of subjects with study drug related adverse events
Maximum concentration (Cmax) of AAT
Area under the concentration curve (AUC) for AAT
Clearance (CL) of AAT
Volume of distribution (V) for AAT
Ctrough of AAT

Full Information

First Posted
January 14, 2019
Last Updated
April 24, 2023
Sponsor
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT03805789
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
Acronym
MODULAATE
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)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 27, 2019 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
March 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring

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
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute-graft-versus-host Disease

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
310 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
AAT (low dose)
Arm Type
Experimental
Arm Description
Open label. Alpha-1 antitrypsin (AAT) is a lyophilized product for intravenous administration
Arm Title
AAT (medium dose)
Arm Type
Experimental
Arm Description
Open label. AAT is a lyophilized product for intravenous administration
Arm Title
AAT (high dose)
Arm Type
Experimental
Arm Description
Open label. AAT is a lyophilized product for intravenous administration
Arm Title
AAT (selected dose from open-label)
Arm Type
Experimental
Arm Description
Double-blind. AAT is a lyophilized product 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
Intervention Description
Alpha-1 antitrypsin is a lyophilized product for intravenous administration.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Albumin solution administered intravenously
Primary Outcome Measure Information:
Title
The time to Grade II-IV acute graft versus host disease (aGVHD) or death
Description
Acute graft vs host disease (aGVHD) will be assessed using the modified Keystone GVHD scoring system.
Time Frame
Through 180 days after hematopoietic cell transplantation (HCT)
Secondary Outcome Measure Information:
Title
Proportion of subjects with lower GI aGVHD or Grade III-IV aGVHD in any organ
Time Frame
Through 180 days after HCT
Title
Proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3
Time Frame
Through Day 60 after HCT
Title
Proportion of subjects with Grade II-IV aGVHD or death
Time Frame
Through 100 days and 180 days after HCT
Title
Proportion of subjects with lower GI aGVHD
Time Frame
Through Days 60, 100 and 180 after HCT
Title
Proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3
Time Frame
Through 100 and 180 days after HCT
Title
Number of deaths (relapse and nonrelapse-related)
Description
Death by any cause
Time Frame
Within 180, 365, and 730 days after HCT
Title
Proportion of subjects with Grade III-IV aGVHD or death
Time Frame
Through Days 60, 100, and 180 days after HCT
Title
Proportion of subjects with moderate-to-severe chronic GVHD
Description
Moderate-to-severe chronic GVHD graded according to NIH scale
Time Frame
Within 180, 365, 545, and 730 days after HCT
Title
Proportion of subjects who have discontinued immune suppression therapies including standard- of- care GVHD prophylaxis and steroid treatment
Time Frame
Within 180 and 365 days after HCT
Title
Time to neutrophil engraftment
Description
Time to the first of 3 consecutive days of absolute neutrophil counts ≥ 500/µL
Time Frame
Through 365 days after HCT
Title
Time to GVHD relapse-free survival
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.
Time Frame
Within 365 and 730 days after HCT
Title
Proportion of subjects with relapse of primary malignancies
Time Frame
Through 180, 365, and 730 days after HCT
Title
Proportion of subjects with Grade II-IV aGVHD with an overall (complete + partial) response, complete response and partial response
Time Frame
Approximately 4 weeks after the initiation of systemic steroids during 8-week Treatment Period
Title
Percent of subjects with study drug related adverse events
Time Frame
Up to 365 days after HCT
Title
Maximum concentration (Cmax) of AAT
Time Frame
Before and up to 72 after infusion of AAT
Title
Area under the concentration curve (AUC) for AAT
Time Frame
Before and up to 72 after infusion of AAT
Title
Clearance (CL) of AAT
Time Frame
Before and up to 72 after infusion of AAT
Title
Volume of distribution (V) for AAT
Time Frame
Before and up to 72 after infusion of AAT
Title
Ctrough of AAT
Time Frame
Before and up to 72 after infusion of AAT

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
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 (ie, anti-thymocyte globulin [ATG], alemtuzumab) for GVHD prophylaxis Planned umbilical cord blood (UCB) transplant
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 Physician
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Scottsdale HH Cancer Transplant
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
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
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
University 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
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Cleveland Cancer Center (University Hospitals UH - Seidman Cancer Center Ireland Cancer Center)
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Centennial Medical Center (TriStar BMT)
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
use central contact
Facility Name
The University of Texas-MD Anderson Cancer Center
City
San Antonio
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
Methodist Hospital
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Seattle Cancer Care Alliance
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
Royal Brisbane and Women's Hospital
City
Herston
State/Province
Queenland
ZIP/Postal Code
4029
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
University Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Uniklinik Köln, lnnere Mediz
City
Köln
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Complejo Hospitalario de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Hospital Universitario Vall d'
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Hospital Regional Universitario de Malaga
City
Málaga
ZIP/Postal Code
29010
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
Hospital Universitario Marqués
City
Santander
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact
Facility Name
The Christie NHS Foundation
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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