View clinical trials related to Myeloproliferative Disorders.
Filter by:This study is being conducted to evaluate the safety, tolerability, dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of INCA033989 administered in participants with myeloproliferative neoplasms.
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.
Myeloproliferative Neoplasms (MPN) are hematological malignancies characterized by the excessive production of myeloid cells. MPN can be complicated by thrombosis and evolution into more aggressive diseases (myelofibrosis and acute leukemia). Aging remains the principal factor determining patients' survival in MPN. In recent years, DNA methylation has appeared as a mean to measure aging via the development of epigenetic clocks that have also been associated with the occurrence of thrombosis and cancer. The epiC project aims at determining epigenetic age of MPN patients and search for an association between this parameter and thrombotic/hematological complications.
This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide, fludarabine, and total-body irradiation (TBI) works in treating patients with hematologic diseases. Giving chemotherapy, such as cyclophosphamide, fludarabine and thiotepa, and TBI before a donor cord blood transplant (CBT) helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening in patients with high-risk hematologic diseases.
The goal of this clinical trial is to determine the effectiveness of Reduced Dose Post-Transplant Cyclophosphamide (PTCy) in patients with hematologic malignancies after receiving an HLA-Mismatched Unrelated Donor (MMUD) . The main question[s] it aims to answer are: - Does a reduced dose of PTCy reduce the occurrence of infections in the first 100 days after transplant? - Does a reduced dose of PTCy maintain the same level of protection against Graft Versus Host Disease (GvHD) as the standard dose of PTCy?
In around 90% of the patients with MPNs, an acquired mutation that promotes JAK/STAT signaling is identified [3, 4]. The JAK/STAT pathway transduces signals from cytokines including erythropoietin, thrombopoietin, and granulocyte colony-stimulating factor.24 A point mutation that activates JAK2, JAK2V617F, is present in around 95% of patients with PV and 40% to 60% of patients with ET and MF
This clinical trial tests whether a geriatric optimization plan (GO!) works to improve survival in patients over 60 with a hematologic malignancy or bone marrow failure syndrome eligible for allogeneic hematopoietic cell transplant. GO! focuses on creating a tailored and specific plan for each patient to make changes in their daily lives. These may include changes to their diet, sleep, activity, medicines, or even referrals to other providers depending on the patient's needs. Studying survival and quality of life in patients over 60 receiving an allogeneic hematopoietic cell transplant may help identify the effects of treatment.
Ambispective, national, multicenter observational cohort study aimed at characterizing the satellite dysimmune manifestations of clonal hematopoiesis, including Vexas (Vacuoles, E1 enzyme, X-linked, Autoinflammatory and Somatic) syndrome.
This study is being conducted to evaluate the safety, tolerability, and dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of INCA033989 administered as a monotherapy or in combination with ruxolitinib in participants with myeloproliferative neoplasms.
Cord blood transplants (CBT) are a standard treatment for adults with blood cancers. MSK has developed a standard ("optimized") practice for cord blood transplant (CBT). This optimized practice includes how patients are evaluated for transplant, the conditioning treatment (standard chemotherapy and total body irradiation therapy) given to prepare the body for transplant, the amount of stem cells transplanted, and how patients are followed during and after transplant.The purpose of this study is to collect information about participant outcomes after CBT following MSK's optimized practice. The researchers will look at outcomes of the CBT treatment such as side effects, disease relapse, GVHD, and immune system recovery after CBT treatment.