Active clinical trials for "Myelodysplastic Syndromes"

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies. Somatic cytogenetic and molecular aberrations and the evolution of subclonal malignant cell populations are responsible for the development and progression of MDS into acute myeloid leukemia. Within only one decade the availability of new genome-wide technologies, like next generation sequencing (NGS), has revolutionized basic research. The routine clinical use of NGS analysis together with well-established diagnostic tools, like chromosome banding analysis or fluorescence in situ hybridization, will substantially add to existing diagnostic and prognostic criteria. This comprehensive combined approach could revolutionize the way we manage patient care. However, little is known about the application of such techniques in routine diagnostics and standards for such analyses are still missing. In a recent publication from the research group, (Article DOI: 10.1002/ajh.25089) it was demonstrated that the analysis of peripheral blood cells (at diagnosis) by NGS is feasible and yields data that are equivalent to the results obtained from bone marrow cells (BMC), which is currently the gold standard for most molecular diagnostic analyses. Not longer depending on the severe and for the patient painful collection of bone marrow aspirates now it is possible to perform comprehensive genetic analysis at short intervals on peripheral blood of MDS patients to detect and closely monitor patterns/pathways of clonal evolution of the malignant cell population in a routine diagnostic setting. It is expected that the obtained data from this study will substantially add to: Understand the functional relevance of identified mutations and the implications of combined mutations. Condense the findings from NGS together with data from established genetic methods (conventional cytogenetics, FISH) to a comprehensive view on MDS genetics and its dynamics considering strengths and weaknesses of each component of this approach. Demonstrate that peripheral blood could be an appropriate sample to perform NGS follow-up studies. In a series of very low, low and intermediate risk MDS patients from Spain it is intended to retrospectively perform NGS (targeted deep sequencing) of diagnosis and consecutive follow-up samples selecting those cases that showed signs of progression of the disease.

This is a registry study in adult patients with newly diagnosed or refractory/relapsed myeloid neoplasms Investigator's sites: 60-70 sites in Germany and Austria Estimated duration of observation of an individual patient: 10 years maximum Objectives To register all patients with acute myeloid leukemia and related precursor neoplasms, acute leukemia of unambiguous lineage, with higher risk myelodysplastic syndromes (MDS with excess blasts 2), and with myeloid neoplasms with germline predisposition, newly diagnosed or relapsed/refractory in all participating centers (completeness) To perform timely analyses of disease-related genetic markers (incidences, treatment recommendations) To assess patient and family history, clinical characteristics and outcome data (event-free survival [EFS], cumulative incidence of relapse [CIR], cumulative incidence of death [CID], overall survival [OS]) To assess biological disease features and correlate with clinical outcome data (prognostic and predictive markers) To store biosamples from all patients (e.g., bone marrow, blood, plasma, normal tissue, e.g., skin biopsy, buccal swap, finger nails, hairs, or sputum) To assess quality of life

Genetic mutations have closely linked to the pathogenesis and prognostication of myeloid cancers. In addition, a number of molecularly targeted agents have been developed in recent years. With the advent of next generation sequencing (NGS), we now are able to detect a wide range of mutations more rapidly, accurately, and economically. In this study, the investigators will use NGS to screen and analyze myeloid-associated gene mutations in the participants, and aim to build up the mutational landscapes of the various myeloid cancers, and investigate how these mutations are linked to clinical outcome.

BACKGROUND Myelodysplastic syndromes (MDS) typically occur in elderly people and with time, a portion of the patients evolve into acute myeloid leukemia (AML). Therefore a risk-adapted treatment strategy is mandatory. Current prognostic scores present limitations, and in most cases fail to capture reliable prognostic information at individual level. STATE OF THE ART Important steps forward have been made in defining the molecular architecture of MDS and gene mutations have been reported to influence survival and risk of disease progression in MDS. Evaluation of the mutation status may add significant information to currently used prognostic scores and a comprehensive analyses of large, prospective patient populations is warranted to correctly estimate the independent effect of each mutation on clinical outcome and response to treatments. AIMS In this project, the investigators will develop a research platform by integrating genomic mutations, clinical variables and patient outcome derived from real-world data obtained from FISiM (Fondazione Italiana Sindromi Mielodisplastiche) clinical network, including 72 hematological centers. This will allow the investigators to: define the clinical utility of mutational screening in the diagnostic work-up and classification of MDS assess the implementation of diagnostic and therapeutic guidelines (appropriateness) in the real-life evaluate the impact of specific interventions (treatments) on clinical outcomes, long-term complications and costs identify predictors of response to specific treatments, and develop precision medicine programs in hematology based on Real World Evidence RWD measure patient-reported outcomes (PRO) and quality of life (QoL) in a real world MDS setting

This phase I trial studies the side effects and best dose of TAK-243 in treating patients with acute myeloid leukemia, or myelodysplastic syndrome, or chronic myelomonocytic leukemia that has come back or that is not responding to treatment. TAK-243 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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.

Myelodysplastic syndromes (MDS) are a pre-leukemic condition with an extremely poor prognosis despite current treatments that justify new therapeutic approaches. Various studies have described the potential involvement of both immune compartment and cellular metabolism in the pathophysiology of MDS. The aim of this study is to determine the specific immune and metabolic profiles of the different classes of MDS and to identify predictive markers of progression/survival/response to therapy.

This study is to determine the safety and preliminary efficacy of sabatolimab in combination with magrolimab and azacitidine in adult participants with 1L unfit Acute Myeloid Leukemia (AML) or with 1L higher risk Myelodysplastic Syndromes (MDS), and sabatolimab in combination with magrolimab in participants with relapsed or refractory (R/R) AML.

This phase I/II open-label, dose-finding, multi-center study will assess safety and primary efficacy of Onureg and Venetoclax combination, to define the optimal biological dose and optimal treatment duration of Onureg to be used along with Venetoclax for further studies in previously untreated patients with higher-risk myelodysplastic syndromes (HR-MDS) not eligible to transplant.

Myelodysplastic syndrome (MDS) is a group of clonal haematopoietic stem cell disorders characterized by ineffective haematopoiesis leading to cytopenia, with a significant risk of progression to acute myeloid leukaemia (AML). Progression to AML and resistance to hypomethylating agents (HMA) are important unmet clinical needs. The pathophysiology of MDS and its progression to AML involve cytogenetic, genetic and epigenetic aberrations, and hence better understanding of the molecular landscape of MDS has important clinical implications. Also, future treatment strategies for MDS may involve exploitation of genetic information in designing more effective therapy encompassing single agents or combinatorial approaches. The proposed cohort study aims to establish a registry of clinical and genomic registry of MDS and secondary AML in Asian patients, which allows the establishment of the mutational profile of patients and prognostic model for survival, as well as exploration of treatment strategies and prediction for treatment response.