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

NCT03188601 | Completed DMC

• 2 other identifiers: 0196-17-RMBA1373
• Study Type: observational
• Target: 27
• Locations: 1 country
• Sites: 4

Brief 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

Conditions

GVHD; Bone Marrow Transplant Failure; Alpha 1-Antitrypsin

Keywords

Graft vs Host Disease; Immune System Diseases; Protease Inhibitors; Alpha 1-Antitrypsin; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Trypsin Inhibitors; Serine Proteinase Inhibitors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Correlation between AAT pattern and survivability, response to immunosuppressive treatment. liver functions, immunocyte activities.

  Up to 1 year

Study Arms (4)

Rambam

Approximately 40 patients in total.No intervention planned.

Soroka

Approximately 10 patients in total.No intervention planned.

Tel Aviv Souraski

Approximately 40 patients in total.No intervention planned.

Jerusalem Hadassah

Approximately 50 patients in total. No intervention planned.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

In every medical center in which a bone marrow transplantation is performed, allogeneic transplantation recipients will be recruited for the trial.

You may qualify if:

• 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

You may not qualify if:

• Patients undergoing immunosuppressive treatment prior to preparation for bone-marrow transplantation.
• Pregnant and disabled patients.

Sponsors & Collaborators

• Rambam Health Care Campus: lead
• Soroka University Medical Center: collaborator
• Tel-Aviv Sourasky Medical Center: collaborator
• Hadassah Medical Organization: collaborator

Study Sites (4)

Hadassah

Jerusalem, Center, 91120, Israel

Location

Tel Aviv Sourasky Medical Center - Ichilov Hospital

Tel Aviv, Center, 6423906, Israel

Location

Rambam MC

Haifa, North, 3525408, Israel

Location

Soroka Medical Center

Beersheba, South, 8410101, Israel

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum samples and peripheral blood mononuclear cells' RNA extracts

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency; Graft vs Host Disease; Immune System Diseases

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Eli Lewis, Professor

  Ben-Gurion University of the Negev

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: June 15, 2017
• Study Start: January 27, 2018
• Primary Completion: February 1, 2022
• Study Completion: August 1, 2022
• Last Updated: April 4, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share

Locations

IL (4)