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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. Read our disclaimer for details. Identifier: NCT02194868
Recruitment Status : Active, not recruiting
First Posted : July 18, 2014
Last Update Posted : March 28, 2019
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief 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

Condition or disease Intervention/treatment
Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies Biological: Recipients Biological: Donors

Detailed 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.

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Study Type : Observational
Estimated Enrollment : 140 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Group/Cohort Intervention/treatment
donors of hematopoietic stem
Adult and minor donors of hematopoietic stem
Biological: Donors
  1. Adult donors :

    • collected 20 ml of blood, (if possible before granulocyte colony-stimulating factor (GCSF) administration)
    • collected 1 ml of the stem cell graft for adult recipient or 2 ml of bone marrow for children recipients These samples will be collected at the same time of those needed for transplant.
  2. Children donors samples

    • collected residual blood
    • 2ml of bone marrow (bottom of tube)

patients requiring allogeneic hema
Adult and minor patients (recipients) requiring allogeneic hema
Biological: Recipients
  1. Adult recipient:

    • collected 20 ml pre-transplant
    • collected 30 ml for adults on day 20 post-transplant at engraftment for cell phenotype,
    • collected 30 ml on days 30, 60, 90, 180, 360 days post-HSCT for cell phenotyping at all time points, functional INKT at day 60 or 90 depending on the number of cells collected and anti-viral ELISPOT studies on days 180 and 360
  2. Children recipients

    • collected residual blood pre-transplant
    • collected residual blood on day 20 post-transplant at engraftment for cell phenotype,
    • collected residual blood on days 20, 30, 90, 180 and 360 post-HSCT

Primary Outcome Measures :
  1. Occurrence of aGVHD [ Time Frame: until 3 years post graft ]
    Patients' clinical files

Secondary Outcome Measures :
  1. 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
Whole blood, hematopoietic stem cell of bone marrow

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The eligible patients will be select by the responsible physicians from clinical teams involved in this study at their BMT staff. These physicians will propose the study to selected patients and provide the informed consent.

Grafts and blood from donors of patients involved in this study will be provided by the different cell therapy departments related to the clinical groups.

Peripheral blood from healthy donors will be obtained from volunteer donations to the "Etablissement Français du Sang" (EFS).


Inclusion Criteria:

  1. Criteria for adults:

    • Allogeneic HSCT with peripheral blood stem cell (PBSC) graft
    • Patients transplanted in cytologic Complete Remission (CR)
    • HLA 10/10 on HLA A, B, Cw, DRB1 and DQ molecules, from an intrafamilial or an unrelated donor
    • - Fludarabine-ivBusulfan-ATG based reduced intensity/toxicity conditioning. Iv Busulfan doses between 6.4 mg/kg to 9.6 mg/kg or Fludarabine - TBI ≤ 8 Gy are accepted. ATG should be thymoglobuline at 5 mg/kg
    • Consent form signed by the patient
    • Consent form signed by the donor
    • Affiliated or beneficiary of a health insurance regimen
  2. Criteria for pediatric patients:

    • Allogeneic HSCT with bone marrow grafts
    • Myeloablative conditioning (either TBI 12 Gy with Cyclophosphamide or iv Busulfan (12.8 mg/kg) and cyclophosphamide or Fludarabine - TBI > 8 Gy)- HLA 10/10 on HLA A, B, Cw, DRB1 and DQ molecules, from an intrafamilial or an unrelated donor
    • Consent form signed by the parents
    • Consent form signed by the donor or his legal representative if it is minor
    • Beneficiary of a health insurance regimen

Exclusion Criteria:

  • History of previous autologous or allogeneic haematopoietic stem cell transplantation
  • Disease non in cytologic CR at transplant
  • Other type of conditioning than Fludarabine-ivBusulfan-ATG based reduced intensity/toxicity.
  • Donor graft with any HLA mismatch including haploidentical and cord blood grafts
  • Graft having one or more mismatch with the recipient HLA

Information from the National Library of Medicine

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 identifier (NCT number): NCT02194868

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Hopital Necker
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
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Principal Investigator: Marie Th Rubio, MD, PhD CHU Nancy
Study Director: Olivier Hermine, MD, PhD Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT02194868     History of Changes
Other Study ID Numbers: NI 12036
First Posted: July 18, 2014    Key Record Dates
Last Update Posted: March 28, 2019
Last Verified: March 2019
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Allogeneic hematopoietic stem cell transplantation,
Immunoregulatory T lymphocytes,
acute graft versus host disease
Additional relevant MeSH terms:
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