View clinical trials related to Myeloproliferative Disorders.
Filter by: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.
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.
The objective of this project is to conduct a pilot randomized trial to assess the preliminary efficacy of a telehealth-delivered Serious Illness Care Program on healthcare communication, patient anxiety and distress, as well as completion of advance directives (specifically MOLST and healthcare proxy forms) for older patients with acute myeloid leukemia, myelodysplastic syndrome, and similar myeloid malignancies.
The purpose of this study is to learn about the impact that the services and programs provided by the Leukemia and Lymphoma Society have among patients with blood cancer, such as access to care, quality of life, and financial burden.
This phase II MyeloMATCH treatment trial compares cytarabine versus (vs.) cytarabine and venetoclax vs. liposome-encapsulated daunorubicin-cytarabine and venetoclax vs. azacitidine and venetoclax for treating patients who have residual disease after treatment for acute myeloid leukemia (AML). Cytarabine is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Liposome-encapsulated daunorubicin-cytarabine is a drug formulation that delivers daunorubicin and cytarabine in small spheres called liposomes, which may make the drugs safer or more effective. Azacitidine is a drug that interacts with DNA and leads to the activation of tumor suppressor genes, which are genes that help control cell growth. This study may help the study doctors find out if the different drug combinations are equally effective to the usual approach of cytarabine alone while requiring a shorter duration of treatment. To decide if they are better, the study doctors will be looking to see if the study drugs lead to a higher percentage of patients achieving a deeper remission compared to cytarabine alone.
This phase II MyeloMATCH treatment trial tests whether the standard approach of cytarabine and daunorubicin in comparison to the following experimental regimens works to shrink cancer in patients with high risk acute myeloid leukemia (AML): 1) daunorubicin and cytarabine liposome alone; 2) cytarabine and daunorubicin with venetoclax; 3) azacitidine and venetoclax. "High-risk" refers to traits that have been known to make the AML harder to treat. Cytarabine is in a class of medications called antimetabolites. It works by slowing or stopping the growth of cancer cells in the body. Daunorubicin is in a class of medications called anthracyclines. It also works by slowing or stopping the growth of cancer cells in the body. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. There is evidence that these newer experimental treatment regimens may work better in getting rid of more AML compared to the standard approach of cytarabine and daunorubicin.
First-line treatment for patients with polycythemia vera, essential thrombocythemia, and pre-myelofibrosis is based on hydroxyurea or pegylated interferon. The objective of treatment is to prevent thrombotic complications and leukemic transformation. Despite overall good response rates, some patients do not respond to treatment and others lose their response over time. Both situations are associated with worse survival and there are to date no clear predictive factors for response although the existence of additional mutations seems unfavorable. In this exploratory study, we hypothesize that biological factors at diagnosis are associated with hematological response at 12 months. We will more specifically study the association between mutational profile, assessed by next-generation sequencing, and cytokine profile with hematological response. This study will help in identifying patients who will not respond to hydroxyurea or pegylated interferon and give the opportunity to try other treatments upfront, in the perspective of precision medicine. On the basic science side, this study will help in understanding the molecular and immunological factors involved in resistance to treatment.
Classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are a family of clonal chronic hematologic malignancies that include. polycythemia vera (PV), essential thrombocythemia (ET), and primary. Myelofibrosis (MF) . The classic MPNs historically have predominantly been diagnosed in older adults, with a median age at diagnosis of 60-72 years . Adults less than 40 years of age make up a largely underrepresented and therefore less studied subset of patients constituting 2.2-6.6% of yearly MPN cases in population- based study. These estimates are lower than incidence rate among patients between 40 and 49 years of age (9.1-10%), and have remained largely unchanged over the past four decades . However, with increasing trends in MPN incidence consequent to increased diagnostic recognition, better pathobiologic understanding, and more frequent JAK2/CALR/MPL mutational testing and newly revised WHO diagnostic criteria, it is conceivable that MPNs may be diagnosed at a higher frequency, in the younger patients, over time.
If for years the treatment strategy of leukemia and related disorders (LRDs, including acute leukemias and predisposition syndromes) has been based solely on whether the patient could receive or not intensive chemotherapy and transplantation, the advent of new targeted or less targeted drugs has led to the development of a growing number of new therapeutic approaches, very often offered to specific patient/disease subsets, justifying the generic term of 'precision medicine'. As an international leukemia center of excellence, THEMA, the French National Center for Precision Medicine in Leukemia (selected as IHUB-2 by the French National Agency for Research), is a care, research, transfer and education initiative located at the Saint-Louis Research Institute (IRSL) in Paris and devoted to precision medicine in leukemia in a real-life environment. The present non-interventional study (eTHEMA) is a pillar of the whole THEMA project. As a prerequisite for precision medicine, this program focuses on individual data collection, aiming to collect high-quality data not only in patients treated into prospective clinical trials, but in every THEMA patient with a special interest in outpatients' care and research. The primary objective of this non-interventional study is to describe the baseline characteristics planned treatments and outcomes of patients newly diagnosed with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS), or myeloproliferative neoplasm (MPN)-related myelofibrosis, when managed and treated according to standard diagnosis and care practices.
Flonoltinib Maleate (FM) targets Janus kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). FM is a dual target inhibitor of JAK2/FLT3.FM has the activity of inhibiting JAK2 signaling pathway, and pharmacodynamics evaluation also confirmed that FM has a good therapeutic effect on the primary splenomegaly model of mice induced by JAK2V617 mutation.Therefore, FM has the potential to treat bone marrow proliferative tumors.The drug is intended to be used in patients with MPN, mainly including medium-risk or high-risk myelofibrosis (FM) (including primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PostPV-MF) and post-primary thrombocythemia myelofibrosis (postET-MF)), Polycythemia vera (PV) and essential thrombocythemia (ET) were the primary causes of thrombocythemia and thrombocythemia. FM has high inhibitory activity against JAK family and FLT3 kinase, suggesting that FM may have a certain therapeutic effect on AML disease.The IC50 of JAK2 kinase inhibition by FM was as low as 0.8 nM, while the IC50 of JAK1, JAK3 and Tyk2 kinase inhibition was 690 nM, 557 nM and 65nM, respectively. The selectivity of JAK2 kinase inhibition by FM was 862.5, 696.3 and 81.3 times, respectively. Therefore, FM showed highly selective inhibition of JAK2 kinase.The IC50 for FLT3 kinase was 15 nM. FM has better inhibitory activity against JAK2 kinase than the listed Ruxolitinib and Fedratinib, and has better selectivity against JAK family.In order to determine whether FM has targets other than JAK2 and Flt3 kinases, we tested FM's inhibitory activity against 100 human kinases that are highly associated with tumors, including some common drug-resistant mutant kinases.The results showed that, except for CDK4/6, LCK and LN, FM had no obvious inhibitory activity against the screened kinases at 0.1 μm, and no other targets were found. In vitro experiments on the proliferation of JAK2-dependent and Flt3-related tumor cell lines with FM showed that the tumor cell lines had a significant inhibitory effect. The IC50 of half of the tumor cell lines was less than 0.5 μm, which was better than or equal to the similar drugs Ruxolitinib and Fedratinib. The effect of FM on tumor cells from MPN patients indicated that FM has the potential to treat MPN disease. In multiple animal models of bone marrow proliferative tumors with JAK2V617F mutations, FM showed superior efficacy and low toxicity (no obvious VISCAL toxicity) than existing drugs on the market, and the tumor inhibition effect of FM showed a good dose-dependent relationship. Objectives of Study Main Purpose: 1. Tolerance and safety of flonoltinib maleate Tablets tablets in patients with bone marrow proliferative tumors; 2. To observe the possible dose-limiting toxicity(DLT) of flonoltinib maleate tablets in patients with bone marrow proliferative tumors,To determine the maximum tolerated dose(MTD) of flonoltinib maleate tablets,To provide the basis for the recommended dose and design scheme of the later clinical trial. Secondary Purpose: 1. To evaluate the pharmacokinetic characteristics of single and repeated oral administration of flonoltinib maleate tablets in patients with bone marrow proliferative tumors; 2. To evaluate the primary efficacy of single and multiple oral flonoltinib maleate tablets in patients with bone marrow proliferative tumors.