View clinical trials related to Leukemia, Myeloid, Acute.
Filter by:An open-label design is adopted in this study. All patients will first undergo pre-screening to determine the mutation status of IDH, and all patients will be assigned to the registry study of the corresponding cohorts of IDH1 and IDH2 based on the pre-screening results. Patients with both IDH1 and IDH2 mutations will be enrolled in the IDH2 cohort. This study is divided into two cohorts. Cohort 1 includes R/R AML patients with IDH1-R132 mutations; Cohort 2 includes R/R AML patients with IDH2-R140 and R172 mutations. The two cohorts are designed independently and will be analyzed separately for statistical hypothesis testing. Patients in both cohorts will be randomized in a 1:1 ratio according to the central Interactive Web Response System (IWRS) into the test or control group, patients in the test group will receive HMPL-306 monotherapy at a dose of 250 mg once daily (QD) (Cycle 1, C1) + 150 mg QD [starting from Cycle 2 (C2)]. Patients in the control group will receive salvage chemotherapy (one of four options) consisting of two intensive chemotherapy regimens (MEC regimen and FLAG ± Ida regimen) and two non-intensive chemotherapy regimens (azacitidine and LoDAC)
To evaluate the feasibility, effectiveness and safety of chidamide combined with venetoclax and azacitidine in the treatment of newly diagnosed acute myeloid leukemia (AML) who are not suitable for intensive chemotherapy.
The primary objective of this study was to evaluate the efficacy of MTBF conditioning regimen of salvageable allo-HSCT in patients with relapsed or refractory acute myeloid leukemia. The secondary purpose of the study was to observe the safety of MTBF regimen in these patients.
The goal of this clinical trial is to learn if participants treated with the experimental drug cusatuzumab added to venetoclax and azacitidine works to treat acute myeloid leukemia (AML) compared to venetoclax and azacitidine. Venetoclax and azacitidine are drugs commonly used to treat AML in patients that are unable to receive chemotherapy to treat AML. The main question the clinical trial aims to answer is does cusatuzumab added to venetoclax and azacitidine prolong the length of time participants live compared to venetoclax and azacitidine?
In our previous retrospective study (SEIFEM 2016 study) we evaluated the incidence of proven/probable invasive aspergillosis (IA) and the role of mold active primary antifungal prophylaxis (PAP) in a "real life" setting of acute myeloid leukemia (AML )patients receiving intensive consolidation therapy. All cases of proven/probable IA, observed during consolidation chemotherapy in adult and pediatric AML patients between 2011 and 2015, were retrospectively collected in a multicenter study involving 38 Italian hematologic centers. We observed 56 (2.2%) cases of IA [43 probable (1.7%) and 13 proven (0.5%)]. The overall mortality rate and the mortality rate attributable to IA (AMR) on day 120 were 16% and 9%, respectively. In multivariate analysis, parameters that influenced the outcome were age ≥60 years and treatment with high doses of cytarabine (HDAC). We also observed that centers involved in this survey had different antifungal policies during the AML consolidation phase. The results from our study show that in a large real-world setting the mold active PAP, with itraconazole or posaconazole, decreases the rate of IA after consolidation course. In SEIFEM 2016 study we demonstrated that the incidence of IA during the AML consolidation is low. However, the mortality is not negligible, mainly in older patients. Further, a sub-analysis in the subset of patients older than 60 years demonstrated that patients who didn't receive mold active prophylaxis had higher incidence of IA than patients who received mold active prophylaxis (15% vs 6%). Therefore, as prophylaxis seems to prevent IA in consolidation, further studies should be performed especially in elderly patients treated with HDAC to confirm our data and to identify the subset of patients who require PAP.
This Phase I/II trial evaluates the safety and preliminary efficacy of DFP-10917 combined with venetoclax in relapsed or refractory acute myeloid leukemia. DFP-10917 is given as a 14-day continuous IV infusion every 28 days, alongside a 14-day oral course of venetoclax following an initial dose ramp-up. The initial phase tests a starting dose of 4 mg/m²/day of DFP-10917 with 400 mg daily of venetoclax. The Data Monitoring Committee reviews toxicity after one treatment cycle. If DLTs are minimal, more patients are added to confirm safety. If the lower dose level shows tolerability, it proceeds to the Phase II expansion to assess the treatment's effectiveness against leukemia using a Simon's two-stage design, targeting up to 17 participants.
HMA maintenance therapy is expected to benefit overall survival (OS) and relapse free survival (RFS) in AML patients with favorable risk.
Mutations in IDH genes are found in numerous cancers and more specifically in acute myeloid leukemia (AML). These mutations target specific amino acids, at positions 140 or 172 of IDH2, and 132 of IDH1. Mutant IDH proteins acquire an abnormal enzymatic activity allowing them to convert α-ketoglutarate (αKG) into D-2 hydroxyglutarate (D-2HG), an oncometabolite which massively accumulates in IDH-mutated cells. At high levels, D-2HG behaves as a competitive inhibitor of αKG and affects the activity of Fe(II)/αKG-dependent dioxygenases. This enzymatic family is involved in a broad spectrum of pathways such as demethylation of histone (JHDM histone demethylases) or DNA (methylcytosine hydroxylases of the TET family). As a result, IDH-mutated cells show altered survival, motility, invasiveness and cell differentiation. In AML, IDH1 mutations might be present in 10-15% at diagnosis Ivosidenib (IVO) a first-in-class, oral, irreversible inhibitor of mutant IDH1 has shown clinical activity as a single agent in studies involving patients with IDH1 mutated relapsed or refractory (R/R) AML (DiNardo et al. 2018) and in front line settings (Montesinos et al. 2022). In phase II clinical trials, IVO yielded 30-35% of complete response rates both in frontline and R/R settings, with long lasting responses. Based on these results, the FDA (Food and Drug Agency) gave its approval for newly-diagnosed AML IDH1mut patients who are ≥ 75 years old or who have comorbidities and in R/R. However, European Medicines Agency (EMA)'s did not approved IVO due to lack of evidences to support the application. Agios Netherlands B.V. (the company that previously own the drug before Servier Laboratories) withdrew its EMA application. Nevertheless, IVO has been available in France through a compassionate use program (CUP), since February 2020 for R/R patients and March 2022 for first line treatment. In this multicentric retrospective study, we aim to evaluate the efficacy and safety of Ivo in two cohorts of IDH1mut AML patients treated within the CUP. The first cohort will concern patients treated in first line setting and the second cohort those treated in R/R disease. Our results might provide new insights regarding IVO in real life settings and support signs of efficacy. This could provide new data for the haematologist community and for another appliance to grant EMA approval of IVO in the setting of R/R IDH1mut AML.
This is an open-label, Phase 1/2 study to determine the safety, tolerability, and efficacy of APL-4098 alone and/or in combination with azacitidine for the treatment of relapsed or refractory (R/R) acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)/AML and MDS-excess blasts (EB). Participants with the MDS-EB subtype will be eligible for the Phase 1 part of the study only.
Test feasibility of an oral maintenance strategy for transplant eligible AML patients in first CR who are medically underserved or have a disadvantage in the CDC SDOH domains