The safety and efficacy of Alpha-1 Antitrypsin (AAT) for the prevention of graft-versus-host disease (GVHD) in patients receiving hematopoietic cell transplant
- Conditions
- Graft versus host diseaseMedDRA version: 20.1Level: PTClassification code 10018651Term: Graft versus host diseaseSystem Organ Class: 10021428 - Immune system disordersTherapeutic area: Body processes [G] - Immune system processes [G12]
- Registration Number
- EUCTR2018-000329-29-IT
- Lead Sponsor
- CSL BEHRING GMBH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 310
1. Male or female subjects, =12 years of age, undergoing HCT for hematological malignancies, including leukemia, lymphoma multiple myeloma, myelodysplastic syndrome, and myeloproliferative neoplasms.
2. Planned myeloablative conditioning regimen (see eligible regimens in Table 9).
3. Subjects must have an unrelated donor matched or mismatched (ie, 7/8 or 6/8) for HLA-A, -B, and -C at intermediate (or higher) resolution, or -DRB1 at high resolution using DNA-based typing.
4. Cardiac function: Ejection fraction at rest = 45.0% or shortening fraction of = 27.0% by echocardiogram or radionuclide scan (MUGA).
5. Estimated creatinine clearance greater than 50.0 mL/minute.
6. Pulmonary function: Diffusing capacity of the lung for carbon monoxide = 50% (adjusted for hemoglobin) of the predicted normal value, and forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) = 50% of the predicted normal value.
7. Liver function: total bilirubin < 2x the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome) and alanine aminotransferase/ aspartate aminotransferase < 3.0x the upper limit of normal.
8. Signed written informed consent obtained before undergoing any study-specific procedures.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 290
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
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.
4. Karnofsky Performance Score < 70%.
5. Active central nervous system involvement by malignant cells.
6. Uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
7. Seropositive for human immunodeficiency virus (HIV)-1 or -2.
8. Seropositive for Human T-Lymphotrophic Virus-I or –II.
9. Active Hepatitis B or C viral replication by polymerase chain reaction.
10. Subjects who have received previous genetically engineered chimeric antigen receptor T-cell therapy (eg, CTL019, tisagenlecleucel, axicabtagene ciloleucel) as these patients are lifelong B-cell deficient and could have increased risk of infection.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of AAT at the selected dose for the prevention of acute GVHD following HCT.;Secondary Objective: 1. To evaluate the efficacy of AAT, including the prevention of post-hematopoietic cell transplant complications. <br>2. To evaluate the safety of AAT, based on incidence of systemic infections and related adverse events. <br>3. To evaluate the pharmacokinetics of AAT in HCT recipients.<br>;Primary end point(s): Grade II-IV acute graft versus host disease-free survival (aGFS)<br>;Timepoint(s) of evaluation of this end point: Through 180 days post-hematopoietic cell transplantation (HCT)<br>
- Secondary Outcome Measures
Name Time Method