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

Acute-graft-versus-host Disease Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03805789
• Other study ID #: CSL964_2001
• Secondary ID: 2018-000329-29
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: March 27, 2019
• Est. completion date: March 2027

Study information

• Verified date: February 2024
• Source: CSL Behring
• Contact: Trial Registration Coordinator
• Phone: 610-878-4000
• Email: clinicaltrials[@]cslbehring.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 310
• Est. completion date: March 2027
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute-graft-versus-host Disease
• Alpha 1-Antitrypsin Deficiency
• Graft vs Host Disease

Intervention

Biological:
• Alpha-1 antitrypsin (AAT)
Alpha-1 antitrypsin is a lyophilized product for intravenous administration.
• Placebo
Albumin solution administered intravenously

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Herston	Queenland
Germany	Uniklinik Köln, lnnere Mediz	Köln
Italy	Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli	Calabria
Italy	University Hospital Catania	Calabria	Catania
Japan	Anjo Kosei Hospital	Anjo-shi
Japan	Tokyo Metropolitan Komagome Hospital	Bunkyo-ku
Japan	Hiroshima University Kasumi Campus	Hiroshima
Japan	Nagoya University Hospital	Nagoya
Japan	Aichi Medical Center Nagoya Daiichi Hospital	Nagoya-shi
Japan	Okayama University Hospital	Okayama-shi
Japan	Osaka International Cancer Institute	Osaka-shi
Japan	Osaka Metropolitan University Hospital	Osaka-shi
Japan	Hokkaido University Hospital	Sapporo
Korea, Republic of	INJE University Haeundae Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Hospital	Seoul
Spain	Hospital Universitario Valle de Hebron	Barcelona
Spain	Marqués de Valdecilla University Hospital	Barcelona
Spain	Salamanca University Hospital	Salamanca
Turkey	Ankara Abdurrahman Yurtaslan	Ankara
Turkey	Turgut Ozal Medicine Center	Battalgazi
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Virginia Health System	Charlottesville	Virginia
United States	University Hospital Cleveland Medical Center	Cleveland	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Johns Hopkins Hospital	Saint Petersburg	Florida
United States	University of Utah Primary Children's Hospital	Salt Lake City	Utah
United States	The University of Texas-MD Anderson Cancer Center	San Antonio	Texas
United States	HonorHealth Scottsdale Shea Medical Center	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Italy,  Japan,  Korea, Republic of,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Through 180 days after hematopoietic cell transplantation (HCT)
Secondary	Proportion of subjects with lower GI aGVHD or Grade III-IV aGVHD in any organ		Through 180 days after HCT
Secondary	Proportion of subjects with severe infections defined by NCI-CTCAE = Grade 3		Through Day 60 after HCT
Secondary	Proportion of subjects with Grade II-IV aGVHD or death		Through 100 days and 180 days after HCT
Secondary	Proportion of subjects with lower GI aGVHD		Through Days 60, 100 and 180 after HCT
Secondary	Proportion of subjects with severe infections defined by NCI-CTCAE = Grade 3		Through 100 and 180 days after HCT
Secondary	Number of deaths (relapse and nonrelapse-related)	Death by any cause	Within 180, 365, and 730 days after HCT
Secondary	Proportion of subjects with Grade III-IV aGVHD or death		Through Days 60, 100, and 180 days after HCT
Secondary	Proportion of subjects with moderate-to-severe chronic GVHD	Moderate-to-severe chronic GVHD graded according to NIH scale	Within 180, 365, 545, and 730 days after HCT
Secondary	Proportion of subjects who have discontinued immune suppression therapies including standard- of- care GVHD prophylaxis and steroid treatment		Within 180 and 365 days after HCT
Secondary	Time to neutrophil engraftment	Time to the first of 3 consecutive days of absolute neutrophil counts = 500/µL	Through 365 days after HCT
Secondary	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.	Within 365 and 730 days after HCT
Secondary	Proportion of subjects with relapse of primary malignancies		Through 180, 365, and 730 days after HCT
Secondary	Proportion of subjects with Grade II-IV aGVHD with an overall (complete + partial) response, complete response and partial response		Approximately 4 weeks after the initiation of systemic steroids during 8-week Treatment Period
Secondary	Percent of subjects with study drug related adverse events		Up to 365 days after HCT
Secondary	Maximum concentration (Cmax) of AAT		Before and up to 72 after infusion of AAT
Secondary	Area under the concentration curve (AUC) for AAT		Before and up to 72 after infusion of AAT
Secondary	Clearance (CL) of AAT		Before and up to 72 after infusion of AAT
Secondary	Volume of distribution (V) for AAT		Before and up to 72 after infusion of AAT
Secondary	Ctrough of AAT		Before and up to 72 after infusion of AAT