The safety and efficacy of Alpha-1 Antitrypsin (AAT) for the prevention of graft-versus-host disease (GVHD) in patients receiving hematopoietic cell transplant

JRCT ID: jRCT2011210064

Registered date:21/01/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Acute graft versus host disease
• Date of first enrollment: 12/07/2022
• Target sample size: 310
• Countries of recruitment: US,Japan,Australia,Japan,Germany,Japan,Italy,Japan,Spain,Japan,UK,Japan,Turkey,Japan,South Korea,Japan
• Study type: Interventional

Intervention(s)

Part 1: Open-label, dose-finding phase (conducted outside Japan)
Cohorts 1 - 3: AAT 90 - 180 mg/kg to be administered intravenously as a loading dose on Day -1, followed by 60 - 120 mg/kg twice weekly (until Day 28), and once weekly thereafter (until Day 56).
Part 2: Double-blind, placebo-controlled part
Cohort 4: AAT 180 mg/kg (or placebo [a commercial albumin product diluted in 5% dextrose]) to be administered intravenously as a loading dose on Day -1, followed by 120 mg/kg twice weekly (until Day 56).

Outcome(s)

• Primary Outcome: Grade II-IV aGVHD-free survival through 180 days after HCT

Secondary Outcome

1. Incidence of lower gastrointestinal (GI) aGVHD or Grade III-IV aGVHD in any organ through 180 days after HCT
2. Incidence of severe infections defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) >= Grade 3 through 60 days after HCT
3. Incidence of Grade II-IV aGVHD or death through 100 and 180 days after HCT
4. Incidence of lower GI aGVHD through 60, 100, and 180 days after HCT
5. Incidence of severe infections defined by NCI-CTCAE >= Grade 3 through 100 and 180 days after HCT
6. Incidence of all-cause mortality, relapse-related and non-relapse-related mortality through 180, 365, and 730 days after HCT
7. Incidence of Grade III-IV aGVHD through 60, 100 and 180 days after HCT
8. Incidence of moderate to severe chronic GVHD through 180, 365, 545, and 730 days after HCT
9. Incidence of discontinuation of immune suppression through 180 and 365 days after HCT
10. Time to neutrophil engraftment
11. GVHD-relapse free survival through 365 and 730 days after HCT
12. Incidence of relapse of primary malignancies through 180, 365, and 730 days after HCT
13. Incidence of overall response, complete response and partial response among subjects with Grade II-IV aGVHD approximately 4 weeks after the initiation of systemic steroids during 8-week Treatment Period
14. Incidence of investigational product-related AEs
15. Pharmacokinetic parameters

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. 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.
2. Planned myeloablative conditioning regimen.

Exclude criteria

1. Prior autologous or allogeneic HCT.
2. 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.
3. Planned umbilical cord blood transplant.

Related Information

• Primary Sponsor: Akama Hideto
• Secondary ID(s): NCT03805789,2018-000329-29