- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03280888
Relevance of Peripheral Cells in the Pathophysiology of Chronic Myelomonocytic Leukemia (CMML)
Chronic Myelomonocytic Leukemia (CMML) is the most frequent of myelodysplastic/myeloproliferative syndromes, as defined by the WHO classification of myeloid malignancies. The median age at diagnosis is around 70 years with a strong male predominance. CMML is a clonal disease of the bone marrow hematopoietic stem cell mainly characterized by persistent monocytosis (>1x109/L) and the presence of immature dysplastic granulocytes in the peripheral blood of CMML patients. Allogeneic stem cell transplantation (ASCT) remains the only curative option in CMML. However, CMML patients are rarely eligible for this kind of therapy, mainly due to their advanced age. The gold standard treatment of CMML thus remains hydroxyurea, which is usually initiated when the disease becomes proliferative, and demethylating agents, which could be efficient in the most aggressive forms of CMML. Nevertheless, the pathogenesis of CMML remains poorly understood and new therapies are urgently needed for patients in treatment failure.
In recent years, a large numbers of gene mutations have been discovered in CMML, none of which are specific of this entity, as they can be encountered with different frequencies in other myeloid neoplasms. These mutated genes encode signaling molecules (NRAS, KRAS, CBL, JAK2, FLT3 and several members of the Notch pathway), epigenetic regulators (TET2, ASXL1, EZH2, IDH1, IDH2,.) and splicing factors (SF3B1, SRSF2, ZRSF2). Mutations in the transcription regulators RUNX1, NPM1 and TP53 have also been reported in CMML. However, the role of these mutations in leukemogenesis is still unclear. CMML is also characterized by defects in monocyte to macrophage differentiation. These defects in monocyte differentiation can be attributed to the presence of immature dysplastic granulocytes that secrete high levels of alpha-defensins HNP1-3 that antagonize the purinergic receptor P2RY6 in CMML patients. These CD14-/CD15+/CD24+ immature granulocytes that belong to the same clone than the leukemic monocytes seem to have immunosuppressive properties ressembling those of the myeloid-derived suppressor cells (MDCS) described in solid tumours. Whether these immature granulocytes contribute to autoimmune manifestations or immunoescape and progression of CMML is a conendrum and remains to be determined.
In this context, the proposed project aims at identifying news insights into the pathophysiology of CMML through a better definition of the phenotype and function of monocytes and immature granulocytes that characterize this pathology.
Study Overview
Status
Conditions
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Laurence Legros, PH
- Phone Number: +33 (0)4 92 03 58 41
- Email: legros.l@chu-nice.fr
Study Locations
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Nice, France, 06000
- Recruiting
- Chu de Nice
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Contact:
- Laurence Legros, PH
- Phone Number: +33 (0)04 92 03 58 41
- Email: legros.l@chu-nice.fr
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Patients newly diagnosed or undergoing treatment in the Clinical Hematology department of the participating establishments
Exclusion Criteria:
- NA
Study Plan
How is the study designed?
Design Details
- Observational Models: Other
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Characterization of molecular mechanisms
Time Frame: at 3 years
|
Characterization of the molecular mechanisms involved in the lack of differentiation of monocytes originating from patients with CML.
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at 3 years
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 13-PP-11
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Myelomonocytic Leukemia
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M.D. Anderson Cancer CenterRecruitingMyelodysplastic Syndrome | Recurrent Chronic Myelomonocytic Leukemia | Recurrent Myelodysplastic Syndrome | Chronic Myelomonocytic Leukemia-1 | Chronic Myelomonocytic Leukemia-2 | Chronic Myelomonocytic Leukemia-0United States
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Mayo ClinicRecruitingRecurrent Chronic Myelomonocytic Leukemia | Refractory Chronic Myelomonocytic LeukemiaUnited States
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M.D. Anderson Cancer CenterRecruitingChronic Myelomonocytic Leukemia | Myelodysplastic/Myeloproliferative Neoplasm | Chronic Myelomonocytic Leukemia-1 | Chronic Myelomonocytic Leukemia-2United States
-
Humanigen, Inc.CompletedChronic Myelomonocytic Leukemia (CMML)United States
-
Gustave Roussy, Cancer Campus, Grand ParisRecruitingMyelomonocytic LeukemiaFrance
-
University of UtahCelgeneCompletedChronic Myelomonocytic LeukemiaUnited States
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Arbeitsgemeinschaft medikamentoese TumortherapieCelgene CorporationUnknownChronic Myelomonocytic LeukemiaAustria
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedChronic Myelomonocytic Leukemia | Chronic Myelogenous LeukemiaUnited States
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Groupe Francophone des MyelodysplasiesJanssen-Cilag Ltd.CompletedChronic Myelomonocytic LeukemiaFrance
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H. Lee Moffitt Cancer Center and Research InstituteIncyte CorporationCompletedMyelomonocytic LeukemiaUnited States