Description:
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).
Title
- Brief Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
CSL964_2001
- SECONDARY ID:
2018-000329-29
- NCT ID:
NCT03805789
Conditions
- Acute-graft-versus-host Disease
Interventions
| Drug | Synonyms | Arms |
|---|
| Alpha-1 antitrypsin (AAT) | Alpha-1 proteinase inhibitor | AAT (high dose) |
| Placebo | | Placebo |
Purpose
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).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| AAT (low dose) | Experimental | Open label. Alpha-1 antitrypsin (AAT) is a lyophilized product for intravenous administration | - Alpha-1 antitrypsin (AAT)
|
| AAT (medium dose) | Experimental | Open label. AAT is a lyophilized product for intravenous administration | - Alpha-1 antitrypsin (AAT)
|
| AAT (high dose) | Experimental | Open label. AAT is a lyophilized product for intravenous administration | - Alpha-1 antitrypsin (AAT)
|
| AAT (selected dose from open-label) | Experimental | Double-blind. AAT is a lyophilized product for intravenous administration | - Alpha-1 antitrypsin (AAT)
|
| Placebo | Placebo Comparator | Albumin solution administered intravenously | |
Eligibility Criteria
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
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 12 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | The time to Grade II-IV acute graft versus host disease (aGVHD) or death |
| Time Frame: | Through 180 days after hematopoietic cell transplantation (HCT) |
| Safety Issue: | |
| Description: | Acute graft vs host disease (aGVHD) will be assessed using the modified Keystone GVHD scoring system. |
Secondary Outcome Measures
| Measure: | Proportion of subjects with lower GI aGVHD or Grade III-IV aGVHD in any organ |
| Time Frame: | Through 180 days after HCT |
| Safety Issue: | |
| Description: | |
| Measure: | Proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3 |
| Time Frame: | Through Day 60 after HCT |
| Safety Issue: | |
| Description: | |
| Measure: | Proportion of subjects with Grade II-IV aGVHD or death |
| Time Frame: | Through 100 days and 180 days after HCT |
| Safety Issue: | |
| Description: | |
| Measure: | Proportion of subjects with lower GI aGVHD |
| Time Frame: | Through Days 60, 100 and 180 after HCT |
| Safety Issue: | |
| Description: | |
| Measure: | Proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3 |
| Time Frame: | Through 100 and 180 days after HCT |
| Safety Issue: | |
| Description: | |
| Measure: | Number of deaths (relapse and nonrelapse-related) |
| Time Frame: | Within 180 and 365 days after HCT |
| Safety Issue: | |
| Description: | Death by any cause |
| Measure: | Proportion of subjects with Grade III-IV aGVHD or death |
| Time Frame: | Through Days 60, 100, and 180 days after HCT |
| Safety Issue: | |
| Description: | |
| Measure: | Proportion of subjects with moderate-to-severe chronic GVHD |
| Time Frame: | Within 180 and 365 days after HCT |
| Safety Issue: | |
| Description: | Moderate-to-severe chronic GVHD graded according to NIH scale |
| Measure: | Proportion of subjects who have discontinued immune suppression therapies including standard- of- care GVHD prophylaxis and steroid treatment |
| Time Frame: | Within 180 and 365 days after HCT |
| Safety Issue: | |
| Description: | |
| Measure: | Time to neutrophil engraftment |
| Time Frame: | Through 365 days after HCT |
| Safety Issue: | |
| Description: | Time to the first of 3 consecutive days of absolute neutrophil counts ≥ 500/µL |
| Measure: | Time to GVHD relapse-free survival |
| Time Frame: | Within 365 days after HCT |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Proportion of subjects with relapse of primary malignancies |
| Time Frame: | Through 180 and 365 days after HCT |
| Safety Issue: | |
| Description: | |
| Measure: | Proportion of subjects with Grade II-IV aGVHD with an overall (complete + partial) response, complete response and partial response |
| Time Frame: | Approximately 4 weeks after the initiation of systemic steroids during 8-week Treatment Period |
| Safety Issue: | |
| Description: | |
| Measure: | Percent of subjects with study drug related adverse events |
| Time Frame: | Up to 365 days after HCT |
| Safety Issue: | |
| Description: | |
| Measure: | Maximum concentration (Cmax) of AAT |
| Time Frame: | Before and up to 72 after infusion of AAT |
| Safety Issue: | |
| Description: | |
| Measure: | Area under the concentration curve (AUC) for AAT |
| Time Frame: | Before and up to 72 after infusion of AAT |
| Safety Issue: | |
| Description: | |
| Measure: | Clearance (CL) of AAT |
| Time Frame: | Before and up to 72 after infusion of AAT |
| Safety Issue: | |
| Description: | |
| Measure: | Volume of distribution (V) for AAT |
| Time Frame: | Before and up to 72 after infusion of AAT |
| Safety Issue: | |
| Description: | |
| Measure: | Ctrough of AAT |
| Time Frame: | Before and up to 72 after infusion of AAT |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 2/Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | CSL Behring |
Last Updated
August 10, 2021
