Clinical trial NCT03805789: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Acute-graft-versus-host Disease
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2019-01-16
Enrollment: 310
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: This study is a phase 2 / 3 prospective, double-blind, randomized, multicenter, placebo-controlled study for prevention of acute GVHD (aGVHD) in participants undergoing an unrelated (matched or single allele mismatched) or matched related allogeneic hematopoietic cell transplantation (HCT).


Eligibility criteria: Inclusion Criteria:

* Male or female participants, \>=12 years of age (\>= 18 years of age for participants at German sites only), undergoing HCT for hematological malignancies, including leukemia, lymphoma, multiple myeloma, myelodysplastic syndrome, and myeloproliferative neoplasms.
* Planned myeloablative conditioning regimen.
* Participants must have a related or unrelated donor as follows:

  * Related donor must be a 6 / 6 match for human leukocyte antigen (HLA)-A, -B, at intermediate (or higher) resolution, and -DR beta 1 (DRB1) at high resolution using deoxyribonucleic acid (DNA)-based typing.
  * Unrelated donor must be 7 / 8 or 8 / 8 match for HLA-A, -B, and -C at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing.

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 transplant.
* Planned use of cyclophosphamide after HCT for GVHD prophylaxis.
* Planned haploidentical donor.

Primary outcomes:
measure: The time to Grade II-IV aGVHD or death
timeFrame: Through 180 days after HCT
Secondary outcomes:
measure: Proportion of participants with lower gastrointestinal (GI) aGVHD or Grade III-IV aGVHD in any organ
timeFrame: Through 180 days after HCT
measure: Proportion of participants with severe infections defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) greater than or equal to (>=) Grade 3
timeFrame: Through Day 60 after HCT
measure: Proportion of participants with Grade II-IV aGVHD or death
timeFrame: Through 100 days and 180 days after HCT
measure: Proportion of participants with lower GI aGVHD
timeFrame: Through Days 60, 100 and 180 after HCT
measure: Proportion of participants with severe infections defined by NCI-CTCAE >= Grade 3
timeFrame: Through 100 and 180 days after HCT
measure: Number of deaths (relapse and nonrelapse-related)
timeFrame: Within 180, 365, and 730 days after HCT
measure: Proportion of participants with Grade III-IV aGVHD or death
timeFrame: Through Days 60, 100, and 180 days after HCT
measure: Proportion of participants with moderate to severe chronic GVHD
timeFrame: Within 180, 365, 545, and 730 days after HCT
measure: Proportion of participants who have discontinued immune suppression therapies including standard of care GVHD prophylaxis and steroid treatment
timeFrame: Within 180 and 365 days after HCT
measure: Time to neutrophil engraftment
timeFrame: Through 365 days after HCT
measure: Time to GVHD relapse-free survival
timeFrame: Within 365 and 730 days after HCT
measure: Proportion of participants with relapse of primary malignancies
timeFrame: Through 180, 365, and 730 days after HCT
measure: Proportion of participants with Grade II-IV aGVHD with an overall (complete + partial) response, complete response and partial response
timeFrame: Approximately 4 weeks after the initiation of systemic steroids during 8-week Treatment Period
measure: Percent of participants with study drug related adverse events
timeFrame: Up to 365 days after HCT
measure: Maximum concentration (Cmax) of AAT
timeFrame: Before and up to 72 after infusion of AAT
measure: Area under the concentration curve (AUC) for AAT
timeFrame: Before and up to 72 after infusion of AAT
measure: Ctrough of AAT
timeFrame: Before and up to 72 after infusion of AAT
measure: Clearance (CL) of AAT
timeFrame: Before and up to 72 after infusion of AAT
measure: Volume of distribution (V) for AAT
timeFrame: Before and up to 72 after infusion of AAT
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Scottsdale Shea Medical Center
state: Arizona
city: Saint Petersburg
country: United States
facility: Johns Hopkins Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospital Cleveland Medical Center
state: Ohio
city: San Antonio
country: United States
facility: The University of Texas-MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Primary Children's Hospital
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queenland
city: Köln
country: Germany
facility: Uniklinik Köln, lnnere Mediz
city: Calabria
country: Italy
facility: University Hospital Catania
state: Catania
city: Calabria
country: Italy
facility: Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
city: Anjo-shi
country: Japan
facility: Anjo Kosei Hospital
city: Bunkyo-ku
country: Japan
facility: Tokyo Metropolitan Komagome Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Kasumi Campus
city: Nagoya-shi
country: Japan
facility: Aichi Medical Center Nagoya Daiichi Hospital
city: Nagoya
country: Japan
facility: Nagoya University Hospital
city: Okayama-shi
country: Japan
facility: Okayama University Hospital
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
city: Osaka-shi
country: Japan
facility: Osaka Metropolitan University Hospital
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Busan
country: Korea, Republic of
facility: INJE University Haeundae Paik Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario Valle de Hebron
city: Barcelona
country: Spain
facility: Marqués de Valdecilla University Hospital
city: Salamanca
country: Spain
facility: Salamanca University Hospital
city: Ankara
country: Turkey
facility: Ankara Abdurrahman Yurtaslan
city: Battalgazi
country: Turkey
facility: Turgut Ozal Medicine Center
Study officials:
affiliation: CSL Behring
name: Study Physician
role: STUDY_DIRECTOR
References: