Dysbiosis and Immune Reconstitution After Allo-HSCT

Not Applicable

• Conditions: Hematopoietic Stem Cell Transplantation

• Registration Number: NCT03616015
• Lead Sponsor: Central Hospital, Nancy, France

Brief Summary

Preliminary (proof of concept), monocentric, interventional, prospective, non-randomized and analytic trial designed to simultaneously explore intestinal microbiota changes and early post-transplant immune reconstitution, and to correlate biological data with clinical data (antibiotics use, stress level, GVHD).

Detailed Description

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the major curative therapeutic approach for hematologic neoplasms. After HSCT, patients have a compromised GI mucosal barrier and an altered microbiota, also called dysbiosis. The later could be due to conditioning or use of broad-spectrum antibiotics, and could be accentuate by stress encountered by patients during their therapy management. Recent data have shown that alterations in the intestinal flora are associated with bad outcome, particularly with graft-versus-host disease (GVHD), bacteremia, and reduced overall survival post-transplantation. How intestinal bacteria can modulate the risk of relapse after HSCT is yet unknown. The scientists hypothesize that the variation of some bacterial taxa may influence post-transplant immune reconstitution, particularly invariant Natural Killer T cells.

Study Timeline

• Study First Submitted: 2018-07-19
• Study First Submitted QC: 2018-08-02
• Study First Posted: 2018-08-06
• Study Start: 2018-12-04
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-30
• Last Update Posted: 2019-02-01
• Primary Completion: 2021-01-31
• Study Completion: 2022-09-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Patients > 18 years affiliated to a social security system
• Patients followed at the hospital of Nancy for a allogeneic hematopoietic cell transplantation (HLA matched donor)
• Graft of peripheral blood stem cell
• GVHD prophylaxis by ciclosporin and antilymphocyte serum +/- mycophenolate mofetil or methotrexate.

Exclusion Criteria

• HIV+ patients
• Patients with active HBV or HCV

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
quality of iNKT reconstitution after HSCT (good/poor)	Day 90,

Secondary Outcome Measures

Name	Time	Method
gut microbiota composition	Day 0, Day 15, Day 30, Day 90	relative abundance of intestinal bacterial taxa
immune reconstitution after HSCT (other immune cells)	Day 15, Day 30, Day 60, Day 90, Day 180, Year 1, Year 2	quantification of Tregs, MDSC, MAIT, T lymphocytes
GVH disease	Day 30, Day 60, Day 90	yes/not
use of antibiotics	Day 0, Day 15, Day 30, Day 60, Day 90	yes/not (molecules, delay, posology)
level of stress	Day -8, Day 15, Day 30, Day 90	test of Cohen
level of anxiety	Day -8, Day 15, Day 30, Day 90	test of Spielberger
quality of iNKT reconstitution after HSCT (good/poor)	Day 15, Day 30, Day 60, Day 180, Year 1, Year2

Trial Locations

Locations (1)

RUBIO Marie-Thérèse; 🇫🇷 Vandoeuvre Les Nancy, France