Acute-graft-versus-host Disease
Conditions
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). This study consisted of two parts. In Part 1, the dose of Alpha1-Proteinase Inhibitor (AAT) to be used in Part 2 was identified based on safety and pharmacokinetic data. The selected dose was subsequently evaluated in Part 2, where the primary objective was to assess its efficacy in preventing aGVHD following HCT.
Interventions
BIOLOGICALAAT
AAT is a lyophilized product for IV administration.
BIOLOGICALPlacebo
Albumin solution administered intravenously
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Proportion of participants with lower GI aGVHD | Through Days 60, 100 and 180 after HCT | — |
| 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 severe infections defined by NCI-CTCAE >= Grade 3 | Through 100 and 180 days after HCT | — |
| Proportion of participants with Grade II-IV aGVHD or death | Through 100 days and 180 days after HCT | — |
Countries
Australia, Germany, Italy, Japan, South Korea, Spain, Turkey (Türkiye), United States
Contacts
STUDY_DIRECTORStudy Physician
CSL Behring
Outcome results
None listed