α1-antitrypsin (AAT) Levels and Functions in Allogeneic Bone Marrow Transplantation and Throughout Progression Into GVHD

GVHD Clinical Trial

— AATGVHD-MARK  

Official title:

Relative Inactivity of Alpha-1-antitrypsin After Bone Marrow Transplantation as a Dynamic Biomarker for GVHD and Prognosis: a Prospective Cohort Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03188601
• Other study ID #: 0196-17-RMB
• Secondary ID: A1373
• Status: Completed
• Start date: January 27, 2018
• Est. completion date: August 1, 2022

Study information

• Verified date: April 2023
• Source: Rambam Health Care Campus
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Create a personalized time and context curve of patient circulating α1-antitrypsin (AAT) levels and functions before hematopoietic stem cell transplantation and throughout progression into GVHD.

PRIMARY ENDPOINT 1. Serum AAT levels and activity, before myeloablative preconditioning, as well as on days (-3),0,7,14,28 from HSCT and every 21 days thereafter.

SECONDARY ENDPOINTS 1. Correlation between AAT patterns and:

• Circulating immune cell activation profiles on day of ablation, 28 days from HSCT and once GVHD is diagnosed.

• Patient survival

• Liver function tests

• GVHD grade: skin manifestations, weight, GI and liver histopathology

• Graft-versus-leukemia effect

Description:

This study will focus on each individual patient from the early point of myeloablative conditioning through HSCT and GVHD. The rationale for this individualized approach is to account for the anticipated variability in patient age and primary disease, background pathology and individual therapeutic course, considering the enormous heterogeneity of this condition. To compensate for this limitation, we intend to create an individualized algorithm, based on a novel dynamic biomarker, i.e., AAT functionality, individualized per patient and placed on a timeline, with the aim of minimizing future occurrences of GVHD, and by using readily available laboratory measurements. The study is designed around patient sample collection, there is no change in standard of care, therefore there is no intervention as well.

Three types of sample tubes will be collected per indicated time point:

• Serum tube for protein levels and enzymatic activity assays.

• EDTA tube for isolation of peripheral blood mononuclear cells (PBMCs), cells will be stimulated and then analyzed by FACS and lysed for RT-PCR

• EDTA tube for whole blood stimulation assay for further FACS analysis and cytokine production measurement.

After donor and recipient informed consent forms were signed, a single blood sample should be obtained from the donor on the day of transplant extraction. Time points for recipient's samples include the day of myeloablation and again immediately prior to HSCT (set as day 0 and possibly -3 in MUDs). Serum and lysed blood samples will be collected on days 7, 14, 28, and every 21 days thereafter, through the development and progression of GVHD (where relevant). Blood samples for FACS will be collected by days 0 and 28. Sample collection is planned to end within 1 year from HSCT, or two months after appearance of symptoms of GVHD, or two months after a change is introduced in the immunosuppressive therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: August 1, 2022
• Est. primary completion date: February 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Candidates for allogeneic transplantation for the first time, scheduled to receive HSCT from HLA-matched sibling or an unrelated matched donor

• Signed informed consent by the donor(Healthy volunteers) and the patient

Exclusion Criteria:

• Patients undergoing immunosuppressive treatment prior to preparation for bone-marrow transplantation.

• Pregnant and disabled patients.

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin
• Alpha 1-Antitrypsin Deficiency
• Bone Marrow Transplant Failure
• GVHD

Locations

Country	Name	City	State
Israel	Soroka Medical Center	Beer sheva	South
Israel	Rambam MC	Haifa	North
Israel	Hadassah	Jerusalem	Center
Israel	Tel Aviv Sourasky Medical Center - Ichilov Hospital	Tel Aviv	Center

Sponsors (4)

Lead Sponsor	Collaborator
Rambam Health Care Campus	Hadassah Medical Organization, Soroka University Medical Center, Tel-Aviv Sourasky Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients progressing into acute or chronic GVHD	Evaluation of patient circulating alpha-1-antitrypsin levels and enzymatic functions as a bio-marker for GVHD progression and grading	Up to 1 year
Secondary	Correlation between AAT pattern and survivability, response to immunosuppressive treatment. liver functions, immunocyte activities.	Correlation between AAT patterns and: Circulating immune cell activation profiles on day of ablation, 28 days from HSCT and once GVHD is diagnosed.; Patient survival; Liver function tests; GVHD grade: skin manifestations, weight, GI and liver histopathology; Graft-versus-leukemia effect	Up to 1 year