Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02194868 |
| Other study ID # |
NI 12036 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 2, 2016 |
| Est. completion date |
January 18, 2022 |
Study information
| Verified date |
September 2022 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The purpose of this study is to confirm that invariant NKT lymphocytes (iNKT) reconstitution
in recipient and in the graft content can predict the outcome of human allogeneic HSCT and to
set up an algorithm for clinical practice that would allow the prediction of acute GVHD risk
according to the quantity and functionality
Description:
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment
in most haematological malignancies. However, its anti-tumor effect (GVT) is often associated
with the development of a graft versus host disease (GVHD) and impaired immune
anti-infectious responses. The predictive and protective features of iNKT cells on the
development of acute GVHD (aGVHD) are not or poorly known in humans and their mechanisms of
action, in particular their potential interactions with the other regulatory effectors and
immune actors of the allogeneic response, remain to be explored.
Our project aims, first, to show that the post-transplant reconstitution and/or the content
of the graft in some immunoregulatory T lymphocytes can early predict the post-transplant
clinical outcome and, second, to explore the underlying immunological mechanisms. For that,
we propose to analyse, in homogeneous cohorts of allografted patients and their donors, the
levels of iNKT cells and other cell populations implicated in the allogeneic immune response
(Tregs, mucosa-associated invariant T (MAIT) cells, delta gammaT and anti-viral specific T
cells) and correlate the results to the post-transplant outcome (GVHD, infections, relapse,
survival). This study will be performed in a cohort of 80 adult allografted patients in four
transplant departments in Paris (hospitals of Necker, Saint Antoine, Saint Louis and La Pitié
Salpétrière) and in a cohort of 60 allografted paediatric patients (Robert Debré hospital in
Paris). Sequential blood samples of patients will be drawn to monitor the immune
reconstitution of the different lymphocyte populations of interest by flow cytometry and
perform functional studies on iNKT (ex vivo expansion capacities and cytokine production).
These analyses will be also performed in the corresponding donors from blood samples
collected before the collection process and from the grafts (obtained by the cell therapy
departments of Necker, La Pitié Salpétrière and Saint Louis hospitals). In addition, we plan
to analyse the effect of, and the mechanisms by which, human cluster of differentiation 4
(CD4) CD4- and CD4+ iNKT cells might control the allogeneic response in vitro, particularly
via their potential interactions with dendritic cells and Tregs. According to the results of
the mechanistic studies, we will test the effect of human subtypes of iNKT cells on the
GVH/GVL affects in a preclinical humanized mouse model of allogeneic HSCT.
The clinical and biological data will be anonymously entered in the electronic case report by
the investigators up to 3 years post transplant.
