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

Phase 2

Recruiting

• Conditions: Acute-graft-versus-host Disease
• Interventions: Biological: Alpha-1 antitrypsin (AAT); Biological: Placebo

• Registration Number: NCT03805789
• Lead Sponsor: CSL Behring

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-01-14
• Study First Submitted QC: 2019-01-14
• Study First Posted: 2019-01-16
• Study Start: 2019-03-27
• Status Verified: 2024-02
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-10
• Primary Completion: 2025-09
• Study Completion: 2027-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 310

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
AAT (low dose)	Alpha-1 antitrypsin (AAT)	Open label. Alpha-1 antitrypsin (AAT) is a lyophilized product for intravenous administration
AAT (medium dose)	Alpha-1 antitrypsin (AAT)	Open label. AAT is a lyophilized product for intravenous administration
Placebo	Placebo	Albumin solution administered intravenously
AAT (high dose)	Alpha-1 antitrypsin (AAT)	Open label. AAT is a lyophilized product for intravenous administration
AAT (selected dose from open-label)	Alpha-1 antitrypsin (AAT)	Double-blind. AAT is a lyophilized product for intravenous administration

Primary Outcome Measures

Name	Time	Method
The time to Grade II-IV acute graft versus host disease (aGVHD) or death	Through 180 days after hematopoietic cell transplantation (HCT)	Acute graft vs host disease (aGVHD) will be assessed using the modified Keystone GVHD scoring system.

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects with Grade II-IV aGVHD or death	Through 100 days and 180 days after HCT
Proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3	Through 100 and 180 days after HCT
Number of deaths (relapse and nonrelapse-related)	Within 180, 365, and 730 days after HCT	Death by any cause
Proportion of subjects with Grade III-IV aGVHD or death	Through Days 60, 100, and 180 days after HCT
Proportion of subjects with moderate-to-severe chronic GVHD	Within 180, 365, 545, and 730 days after HCT	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	Within 180 and 365 days after HCT
Proportion of subjects with lower GI aGVHD or Grade III-IV aGVHD in any organ	Through 180 days after HCT
Proportion of subjects with lower GI aGVHD	Through Days 60, 100 and 180 after HCT
Time to neutrophil engraftment	Through 365 days after HCT	Time to the first of 3 consecutive days of absolute neutrophil counts ≥ 500/µL
Time to GVHD relapse-free survival	Within 365 and 730 days after HCT	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 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
Proportion of subjects with relapse of primary malignancies	Through 180, 365, and 730 days after HCT
Percent of subjects with study drug related adverse events	Up to 365 days after HCT
Area under the concentration curve (AUC) for AAT	Before and up to 72 after infusion of AAT
Clearance (CL) of AAT	Before and up to 72 after infusion of AAT
Volume of distribution (V) for AAT	Before and up to 72 after infusion of AAT
Ctrough of AAT	Before and up to 72 after infusion of AAT
Maximum concentration (Cmax) of AAT	Before and up to 72 after infusion of AAT

Trial Locations

Locations (34)

Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli; 🇮🇹 Calabria, Italy

HonorHealth Scottsdale Shea Medical Center; 🇺🇸 Scottsdale, Arizona, United States

Johns Hopkins Hospital; 🇺🇸 Saint Petersburg, Florida, United States

University Hospital Catania; 🇮🇹 Calabria, Catania, Italy

Uniklinik Köln, lnnere Mediz; 🇩🇪 Köln, Germany

Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Kansas Cancer Center; 🇺🇸 Westwood, Kansas, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

University of Michigan Medical Center; 🇺🇸 Ann Arbor, Michigan, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

University Hospital Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

The University of Texas-MD Anderson Cancer Center; 🇺🇸 San Antonio, Texas, United States

University of Utah Primary Children's Hospital; 🇺🇸 Salt Lake City, Utah, United States

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

University of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States

Royal Brisbane and Women's Hospital; 🇦🇺 Herston, Queenland, Australia

Tokyo Metropolitan Komagome Hospital; 🇯🇵 Bunkyo-ku, Japan

Osaka International Cancer Institute; 🇯🇵 Osaka-shi, Japan

INJE University Haeundae Paik Hospital; 🇰🇷 Busan, Korea, Republic of

Pusan National University Hospital; 🇰🇷 Busan, Korea, Republic of

Osaka Metropolitan University Hospital; 🇯🇵 Osaka-shi, Japan

Hospital Universitario Valle de Hebron; 🇪🇸 Barcelona, Spain

Gachon University Gil Medical Center; 🇰🇷 Incheon, Korea, Republic of

Marqués de Valdecilla University Hospital; 🇪🇸 Barcelona, Spain

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Turgut Ozal Medicine Center; 🇹🇷 Battalgazi, Turkey

Ankara Abdurrahman Yurtaslan; 🇹🇷 Ankara, Turkey

Salamanca University Hospital; 🇪🇸 Salamanca, Spain

Anjo Kosei Hospital; 🇯🇵 Anjo-shi, Japan

Hiroshima University Kasumi Campus; 🇯🇵 Hiroshima, Japan

Aichi Medical Center Nagoya Daiichi Hospital; 🇯🇵 Nagoya-shi, Japan

Nagoya University Hospital; 🇯🇵 Nagoya, Japan

Okayama University Hospital; 🇯🇵 Okayama-shi, Japan

Hokkaido University Hospital; 🇯🇵 Sapporo, Japan