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

NCT02766153 | Terminated

• 1 other identifier: 14-PP-02
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Myeloproliferative Disorders

Outcome Measures

Primary Outcomes (1)

• Characteristics of cell CD34 + tumor from patients with SMP

  Establishment of a stem cell CD34 + tumor bank from patients with SMP

  5 years

Secondary Outcomes (1)

• Characteristics of the variation of TKI on CD4+ stem cells

  5 years

Study Arms (2)

patients

healthy volunteers

intrafamily marrow donors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Patients with LLC (chronic myeloid leukemia)

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead
• Centre National de la Recherche Scientifique, France: collaborator

Study Sites (1)

CHU de Nice

Nice, 06200, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

bone marrow

MeSH Terms

Conditions

Myeloproliferative Disorders

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2016
• First Posted: May 9, 2016
• Study Start: May 1, 2016
• Primary Completion: April 1, 2020
• Study Completion: December 1, 2020
• Last Updated: February 5, 2024

Record last verified: 2018-06

Locations

FR (1)