NCT06022341Not yet recruiting
MultiOmic characteriZation of Acute Myeloid Leukemia Evolving From myelopRoliferative Neoplasm to Identify New Targeted Therapeutic Strategies
Source: ClinicalTrials.gov · Last updated 1 Sept 2023 · Not updated for over 12 months - ask the site whether it is still open
Brief summary (registry, in English)
Myeloproliferative neoplasms (MPN) are chronic myeloid malignancies characterized by a risk of evolution to acute myeloid leukemia (AML). This unpredictable complication is associated with a grim outcome with median overall survival ranging between 2 to 10 months. To date, even allogeneic transplantation fails to significantly improve the prognosis. Biological and molecular mechanisms driving leukemic transformation are complex, ill-defined, and heterogeneous between patients. The investigator hypothesize that deciphering the molecular heterogeneity of post-MPN AML may lead identifying efficient drugs targeting of the most relevant leukemogenic pathways. Our main objective is to identify new targeted therapeutic approaches in post-MPN AML through in-depth characterization of the dysregulated pathways. The investigator will first characterize in an already annotated cohort of 120 post-MPN AML homogeneous patients subgroups using comprehensive multiomic analyses. Dysregulated pathways will be identified in each subgroup using the omics data and single-cell RNA-sequencing will be performed in a subset of patients in each subgroup. A customised drug-panel will be derived from the dysregulated pathway for an ex vivo drug screening, which will use a flow-cytometry read-out enabling to identity drug effect on cells survival, differentiation, and stemness. The 3 most promising drugs will be validated in a preclinical in vivo model of patient's derived xenograft (PDX) and their impact on clonal architecture will be studied in primary cell cultures using single-cell DNA-sequencing. Overall, this proposal may provide a better understanding of MPN leukemic transformation mechanisms and provide a path for personalized therapies. Our findings may therefore pave the way to drugs development in post-MPN AML that would provide a rationale for implementation of early clinical trials in these dreadful diseases.
- Status (registry)
- Not yet recruiting
- Study type
- Interventional
- Enrollment
- 120 (estimated)
- First submitted
- 22 Aug 2023
- Start date
- 15 Oct 2023
- Primary completion date
- 31 Dec 2027
- Lead sponsor
- University Hospital, Angers
- NCT number
- NCT06022341
What you commit to
- Study type: Interventional
- Planned participants: 120
- From 15 Oct 2023 to the primary completion date, 31 Dec 2027
- No sites listed in no country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Other
- \- Patient not affiliated to the French health insurance
Who the study is looking for
- Patients with a prior diagnosis of MPN: polycythemia vera, essential thrombocythemia or primary myelofibrosis according to the WHO criteria
- Acute myeloid leukemia evolution defined by ≥ 20% of blasts cells
- Available material from bone marrow sampling at the time of leukemic transformation (i.e. ≥ 20% of blasts cells): DNA (1µg), RNA (500ng) +/- frozen mononuclear cells in DMSO for a subset of 60 patients (2 vials of at least 8 millions cells).
- Informed consent (or requalification procedure)
Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers
This page is information, not medical advice. Discuss any trial with your doctor.