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

• AAT (Biological), also known as Alpha-1 proteinase inhibitor, Respreeza: AAT is a lyophilized product for IV administration.
• Placebo (Biological): Albumin solution administered intravenously

Primary outcomes

• The time to Grade II-IV aGVHD or death [Through 180 days after HCT]: Acute GVHD will be assessed using the Harris scoring system.

Secondary outcomes

• Proportion of participants with lower gastrointestinal (GI) aGVHD or Grade III-IV aGVHD in any organ [Through 180 days after HCT]
• 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 [Through Day 60 after HCT]
• Proportion of participants with Grade II-IV aGVHD or death [Through 100 days and 180 days after HCT]
• Proportion of participants with lower GI aGVHD [Through Days 60, 100 and 180 after HCT]
• Proportion of participants 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 participants with Grade III-IV aGVHD or death [Through Days 60, 100, and 180 days after HCT]
• Proportion of participants with moderate to severe chronic GVHD [Within 180, 365, 545, and 730 days after HCT]: Moderate to severe chronic GVHD graded according to National Institutes of Health (NIH) scale.
• Proportion of participants who have discontinued immune suppression therapies including standard of care GVHD prophylaxis and steroid treatment [Within 180 and 365 days 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 III-IV acute GVHD, 2) moderate-severe chronic GVHD, 3) primary malignancy relapse or 4) death.
• Proportion of participants with relapse of primary malignancies [Through 180, 365, and 730 days after HCT]
• Proportion of participants 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]
• Percent of participants with study drug related adverse events [Up to 365 days after HCT]
• Maximum concentration (Cmax) of AAT [Before and up to 72 after infusion of AAT]
• Area under the concentration curve (AUC) for AAT [Before and up to 72 after infusion of AAT]
• Ctrough of 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]

Sex: All, ages: 12 Years to any

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.

• Study Physician, Study director, CSL Behring

NIH grants: 2018