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Exploring the Mechanisms of Resistance of Stem Cells Myeloproliferative Opposite of Tyrosine Kinase Inhibitors in 3d Model Niche Endosteal

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ClinicalTrials.gov Identifier: NCT02766153
Recruitment Status : Not yet recruiting
First Posted : May 9, 2016
Last Update Posted : May 9, 2016
Sponsor:
Collaborator:
Centre National de la Recherche Scientifique, France
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice

Brief Summary:

Myeloproliferative disorders (MPD) include chronic myeloid leukemia (CML) (Ph +) and essential thrombocythemia (ET), the polycythemia vera (PV), myelofibrosis (MF) called SMP Ph. CML is the ultimate model of carcinogenesis. SMP is a characterized by a malignant monoclonal proliferation of a pluripotent hematopoietic progenitor determined by the presence of a balanced translocation between chromosomes 9 and 22 (Ph chromosome) which leads to major changes of a large number of cell functions. Investigators now believe that within the bone marrow exist two types of "hematopoietic niches' niche osteoblastic / endosteal and vascular niche, controlling the maintenance and differentiation of hematopoietic stem cell pool. The endosteal niche, is a hypoxic region near the endosteal trabecular, which provides protection to deeply dormant stem cells. Data from the literature suggest that in the SMP, especially CML, the interaction of malignant stem cells with the microenvironment niche Endosteal could favor their survival and resistance to treatment. The therapeutic management of CML was upset by the use of tyrosine kinase inhibitors (TKIs). However, despite these advances, even in situations of undetectable residual disease, it has been observed relapses of the disease stopped TKI leaving suggest that there is a resistance of leukemic stem cell to TKI.

Work in the group Bipoa "Bio Engineering and Pathophysiology Osteo-Articular" helped develop a 3D model of ex vivo bone formation, which can mimic the endosteal niche. the goal is to apply this model to the SMP of hematopoiesis by referring to normal hematopoiesis. it will be tested the hypothesis that the endosteal ex vivo recess of the 3D modeling allows to highlight a special interaction can promote the persistence of the leukemia stem cell despite the use of effective therapies.


Condition or disease
Myeloproliferative Disorders

Study Type : Observational
Estimated Enrollment : 200 participants
Time Perspective: Prospective
Study Start Date : May 2016
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Group/Cohort
patients
healthy volunteers
intrafamily marrow donors



Primary Outcome Measures :
  1. Characteristics of cell CD34 + tumor from patients with SMP [ Time Frame: 5 years ]
    Establishment of a stem cell CD34 + tumor bank from patients with SMP


Secondary Outcome Measures :
  1. Characteristics of the variation of TKI on CD4+ stem cells [ Time Frame: 5 years ]
    Compare in vitro, in traditional culture or in a 3D environment mimicking endosteal niche, the effect of first and second generation TKIs on CD34 + stem cells made from patients with SMP or healthy volunteer donors


Biospecimen Retention:   Samples Without DNA
bone marrow


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The patients selected for this study, which will continue over a period of five years, corresponding to all newly diagnosed patients or SMP during TKI treatment in the clinical hematology department of Nice University Hospital and associated centers. The recruitment of three years should be 200 patients. Healthy donors are intra-family donor marrow taken to operating room under general anesthesia as part of their marrow donation. These healthy donors have also already signed a consent for their donation, including research referred to levies.
Criteria

Inclusion Criteria:

  • Patients with LLC (chronic myeloid leukemia)

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): NCT02766153


Contacts
Contact: Laurence LEGROS, PH legros.l@chu-nice.fr
Contact: Irit TOUITOU touitou.i@chu-nice.fr

Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Centre National de la Recherche Scientifique, France

Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT02766153     History of Changes
Other Study ID Numbers: 14-PP-02
First Posted: May 9, 2016    Key Record Dates
Last Update Posted: May 9, 2016
Last Verified: April 2016

Additional relevant MeSH terms:
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases