Immunoregulatory T Lymphocytes Subtypes and Haematopoietic Stem Cell Transplantation (HSCT) (REG-Allo)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02194868|
Recruitment Status : Recruiting
First Posted : July 18, 2014
Last Update Posted : December 21, 2017
|Condition or disease||Intervention/treatment|
|Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies||Biological: Recipients Biological: Donors|
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 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.
|Study Type :||Observational|
|Estimated Enrollment :||140 participants|
|Official Title:||Role and Interactions Between Immunoregulatory T Lymphocytes Subtypes After Allogeneic Haematopoietic Stem Cell Transplantation (HSCT): Identification of New Partners Implicated on the Development of GVT (Graft Versus Tumor) and Anti-infectious Responses Without GVHD (Graft Versus Host Disease)|
|Actual Study Start Date :||February 2, 2016|
|Estimated Primary Completion Date :||April 2020|
|Estimated Study Completion Date :||September 2020|
donors of hematopoietic stem
Adult and minor donors of hematopoietic stem
patients requiring allogeneic hema
Adult and minor patients (recipients) requiring allogeneic hema
- Occurrence of aGVHD [ Time Frame: until 3 years post graft ]Patients' clinical files
- iNKT and effectors of the immune allogeneic response [ Time Frame: until 3 years post graft ]Correlation between iNKT and regulatory effectors of the immune allogeneic response (Assessed by multiparametric flow cytometry of blood sample)
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02194868
|Contact: Valérie Jolaine, Master 2||+331 42 19 28 email@example.com|
|Contact: Laurence Lecomte, PhD||+33 1 71 19 64 firstname.lastname@example.org|
|Paris, France, 75015|
|Contact: Olivier Hermine, MD, PhD +33 1 44 49 5198 email@example.com|
|Contact: laurence Lecomte, PhD +33171196494 firstname.lastname@example.org|
|Principal Investigator:||Marie Th Rubio, MD, PhD||CHU Nancy|
|Study Director:||Olivier Hermine, MD, PhD||Assistance Publique - Hôpitaux de Paris|