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Expansion of Invariant NKT Cells for a Cell Immunotherapeutic Approach Allowing the Control of Graft Versus Host-disease and Preserving the Graft Versus Leukemia Effect After Allogeneic Hematopoietic Stem Cell Transplantation (ExpiNKT1)

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ClinicalTrials.gov Identifier: NCT03605953
Recruitment Status : Not yet recruiting
First Posted : July 30, 2018
Last Update Posted : July 30, 2018
Sponsor:
Information provided by (Responsible Party):
Central Hospital, Nancy, France

Brief Summary:

Allogeneic hematopoietic stem cell (HSC) transplantation remains the most efficient cellular immunotherapeutic approach for the treatment of myeloid hematological malignancies. However, its use is hampered by the risk of developing acute graft-versus-host disease (aGVHD). Invariant NKT cells (iNKT) represent a good candidate of immuno-regulatory cells that could control GVHD while preserving the anti-leukemic effect (GVL) of HSCT. Our team have shown that higher numbers and expansion capacity of CD4- iNKT cells contained in the HSC graft were associated with reduced risk of aGVHD but preserved GVL effect and that some healthy donors have low numbers and expansion capacity CD4- iNKT cells 1.

The objective of this project is to develop a strategy allowing to expand human CD4- iNKT cells from healthy donors of HSC grafts that would be transposable to GMP-validated cell production. Our team proposes to first determine the best strategy to expand the CD4- iNKT cell subset from G-SCF mobilized peripheral blood stem cells (PBSC) obtained from healthy donors, at little scale using cultures GMP validated conditions, by comparing the convention expansion protocol using IL-2 alone to IL-7, IL-15, IL-4 or combination of those cytokines involved in the expansion of T cells and by culturing the cells in a bioreactor. Our team will then explore the characteristics of cells after expansion in terms of phenotype, transcription signature and functions in vitro (in mixed lymphocyte reaction) and in vivo in a well-established xenogeneic model of GVHD.


Condition or disease
Allogeneic Hematopoietic Stem Cell (HSC) Transplantation

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Study Type : Observational
Estimated Enrollment : 134 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Expansion of Invariant NKT Cells for a Cell Immunotherapeutic Approach Allowing the Control of Graft Versus Host-disease and Preserving the Graft Versus Leukemia Effect After Allogeneic Hematopoietic Stem Cell Transplantation
Estimated Study Start Date : October 1, 2018
Estimated Primary Completion Date : October 1, 2019
Estimated Study Completion Date : April 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia




Primary Outcome Measures :
  1. Kinetic of iNKT cells (flask culture) [ Time Frame: from day 0 to day 14 ]
  2. time of culture to reach the maximal expansion factor [ Time Frame: day 14 ]
  3. Percentage of cells alive [ Time Frame: day 14 ]
  4. Percentages of CD4- iNKT cells capable of producing IFN-γ after expansion [ Time Frame: day 14 ]

Secondary Outcome Measures :
  1. Kinetic of iNKT cells(culture in bioreactor system) [ Time Frame: From day 0 to day 14 ]
  2. Expression of cytokine receptors CD4- iNKT data [ Time Frame: day 14 ]
  3. Expression of cytokine receptors CD4+ iNKT data [ Time Frame: day 14 ]
  4. transcriptional pattern CD4- iNKT data [ Time Frame: day 14 ]
  5. Transcriptional pattern CD4+ iNKT [ Time Frame: day 14 ]
  6. Percentage of recovery of CD4- iNKT cells after immunomagnetic selection [ Time Frame: day 14 ]
  7. Proportion of Th1 producing T cells stimulated by allogeneic dendritic cells [ Time Frame: day 6 in a mixed lymphocyte reaction ]
  8. Proportion of Th17 producing T cells stimulated by allogeneic dendritic cells [ Time Frame: day 6 in a mixed lymphocyte reaction ]
  9. Proportion of mice protected from GVHD mortality in a xeno-GVHD mouse model [ Time Frame: survival proportions between day 28 and day 60 post-transplantation ]
  10. Ratio of iNKT/T cells to control xeno-GVHD mortality [ Time Frame: survival proportions between day 28 and day 60 post-transplantation ]
  11. Proportion of mice protected from leukemia development [ Time Frame: survival proportions between day 28 and day 60 post-transplantation ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
healthy donors of HSCT
Criteria

Inclusion Criteria:

Hematopoietic stem cells :

  • from major donors after mobilization by G-CSF, informed of the research and not having opposed it
  • Collected after verification by the cell therapy centre of the presence of a sufficient quantity of CSH for transplantation

Exclusion Criteria:

Hematopoietic stem cells (HSCs) from donors seropositive for HIV, HCV, HTLV1 and HBV (except post-vaccination profile)


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 ClinicalTrials.gov identifier (NCT number): NCT03605953


Contacts
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Contact: Marie-Thérèse RUBIO, PU-PH 0383153282 ext +33 m.rubio@chru-nancy.fr

Sponsors and Collaborators
Central Hospital, Nancy, France

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Responsible Party: Central Hospital, Nancy, France
ClinicalTrials.gov Identifier: NCT03605953     History of Changes
Other Study ID Numbers: PRTK2017/ExpiNKT-RUBIO/VS
First Posted: July 30, 2018    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: July 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Central Hospital, Nancy, France:
Cell therapy
immuno-modulation
immunotherapy
Hematology

Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases