View clinical trials related to Leukemia, Myeloid.
Filter by:The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of SNDX-5613 in combination with intensive chemotherapy in participants with newly diagnosed acute myeloid leukemia (AML) harboring alterations in KMT2A, NPM1, or NUP98 genes.
Acute myeloid leukemia (AML) is a malignancy of aging endowed with poor prognosis. The combination of the hypomethylating agent azacitidine (AZA) with the BCL-2 inhibitor venetoclax (VEN) is the first-line treatment of older AML patients but is endowed with substantial resistance. The project leverages functional precision oncology, single-cell studies and mouse experiments to dissect the mechanisms of primary and adaptive resistance to AZA/VEN. The primary objective is to prospectively validate an ex vivo drug sensitivity testing (DST) assay as predictor of primary resistance to first-line AZA/VEN in 100 unfit AML patients. The study will also explore whether newer DST assays with enhanced niche mimicry can improve on the standard assay. By serially interrogating the short-term fate of both leukemic and immune cells upon AZA/VEN exposure in patients primed towards refractoriness, transient or prolonged remission, the aim is to dissect the cell-intrinsic and immune-mediated mechanisms of primary versus adaptive resistance. A parallel flow cytometry study will interrogate the role of senescence in AZA/VEN activity. These translational studies will be mirrored by experiments in a transplantable AML model derived from syngeneic mice harboring the age-related Tet2-/- leukemia-predisposing genotype. Lineage tracing single-cell experiments will backtrack AZA/VEN resistance to determine whether it is driven by selection or adaptation. The actionable stress sensor Pml will be invalidated in the same model to determine whether Pml-driven senescence contributes to AZA/VEN anti-leukemic activity in vivo. The project will pave the way to the clinical implementation of functional precision oncology in a high-risk malignancy. By simultaneously interrogating cell-intrinsic and immune-mediated drug resistance in vivo in a prospective patient cohort mirrored by controlled mice experiments, the project will provide a framework for the integrative analysis of drug resistance in cancers.
This phase I trial tests the safety, side effects, and best dose of SNDX-5613 and gilteritinib for treating patients with acute myeloid leukemia that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory) and has a mutation in the FLT3 gene along with either a mutation in the NMP1 gene or a type of mutation called a rearrangement in the MLL gene. SNDX-5613 is in a class of medications called menin inhibitors. It works by blocking the action of mutated MLL and NMP1 proteins that signal cancer cells to multiply. Gilteritinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of mutated FLT3 proteins that signal cancer cells to multiply. Giving SNDX-5613 with gilteritinib may be safe, tolerable and/or effective in treating patients with relapsed/refractory FLT3 mutated acute myeloid leukemia.
Chidamide in combination with venetoclax and azacitidine (VAC) were expected to improve remission rate of patients following to VA regimen treatment failure.
This non-interventional study (NIS) was a retrospective chart review analyzing existing data from patients participating in the asciminib MAP.
This is a single-centre, single-arm, open-label, first-in-human (FIH) study to evaluate the safety, tolerability and preliminary efficacy of universal Off-the-shelf CAR-NK cells targeted CD123 (JD123 injection) in the treatment of refractory or relapsed CD123-positive acute myeloid leukemia (AML).
The investigators aimed to reveal the relationship between serum markers of pyroptosis, GVHD biomarkers and endothelial damage markers in patients who were planned for allogeneic stem cell transplantation for AML and developed GVHD during follow-up. Secondary outcomes of the study were to demonstrate the role of pyroptosis in the pathophysiology of GVHD and transplantation-associated endothelial injury using serum plasma samples; the efficacy of GVHD biomarkers used to demonstrate organ-specific involvement; and the efficacy of GVHD biomarkers and endothelial injury markers in predicting the development of GVHD, transplantation-associated endothelial injury and non-relapse mortality.
This study is designed as a single arm open label traditional Phase I, 3+3, study of CD4-redirected chimeric antigen receptor engineered T-cells (CD4CAR) in patients with relapsed or refractory AML. the study will evaluate safety in this patient population and also the presence of efficacy signal described by elimination of residual disease to qualify patients for stem cell transplant.
This phase I trial tests the side effects and best dose of total marrow lymphoid irradiation along with chemotherapy, with fludarabine and melphalan, with or without thiotepa, in combination with Orca-T cells for patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS). Total marrow and lymphoid irradiation is a targeted form of total body irradiation that uses intensity-modulated radiation therapy to target marrow, lymph node chains, and the spleen. It is designed to reduce radiation-associated side effects and maximize the radiation therapeutic effect. Giving chemotherapy with medications such as thiotepa, fludarabine, and melphalan before a treatment with stem cells helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Orca-T cells take cells from a donor and remove some of the T cells and replace them with partially engineered T cells in order to induce better tolerance in patients. Giving total marrow and lymphoid irradiation and chemotherapy followed by Orca -T cells may be an effective treatment for patients with AML, ALL or MDS.
To find a recommended dose of ASTX727 (cedazuridine/decitabine) in combination with venetoclax for pediatric patients with relapsed AML.