Azacitidine (AZA)

The purpose of this study is to assess how bleximenib and Venetoclax (VEN)+ Azacitidine (AZA) works as compared to placebo and VEN+AZA alone for the treatment of participants with newly diagnosed Acute Myeloid Leukemia (AML) with a mutation in the NPM1 or KMT2A gene.

Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with eligible genetic alterations. Ziftomenib is a type of therapy known to target the menin pathway in cancer cells. This protocol has 2 separate studies that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) AML treatments in patients with certain genetic mutations who have not received any treatment for their AML. In the first study, the Nonintensive Therapy Study, older patients or those with serious medical problems will receive the SOC therapies venetoclax (ven) and azacitidine (aza), plus either ziftomenib or a placebo. In the second study, the Intensive Therapy Study, medically fit patients will receive (a) the SOC therapies cytarabine and daunorubicin, plus either ziftomenib or a placebo during a first treatment phase called induction, (b) cytarabine plus either ziftomenib or a placebo during a second treatment phase called consolidation, and (c) ziftomenib or a placebo during a third treatment phase called maintenance. The physician will determine which study is the appropriate treatment for the patient, but neither the patient nor their physician will know whether the patient has been assigned to receive ziftomenib or a placebo. This design is called "double-blinded".

ETP-ALL like patients have poor outcomes and prognosis, and the optimal therapeutic approaches are poorly characterized. The goal of this clinical trial is to evaluate the efficacy and safety of the venetoclax combined with azacitidine, chidamide, vindesine, and dexamethasone regimen in newly diagnosed ETP-ALL like patinets (including ETP-ALL, near ETP-ALL and T-ALL with myeloid mutations) .

The purpose of this study is to evaluate whether HLA-mismatched donor G-CSF mobilized peripheral blood mononuclear cell (GPBMC) infusion with venetoclax-containing regimens (microtransplant, MST) could improve survival in adult patients with newly diagnosed acute myeloid leukemia (AML).

This is a therapeutic intervention trial evaluating the clinical utility of a novel blood-based epigenetic biomarker-genome-wide 5-hydroxymethylcytosine (5hmC) in cell-free DNA (cfDNA)-for assessing measurable residual disease (MRD) in patients with newly diagnosed acute myeloid leukemia (AML). The study compares the efficacy of hypomethylating agent (HMA)-based therapy versus intensive induction chemotherapy, using the 5hmC biomarker to guide post-induction treatment decisions. Approximately 112 adult patients will be enrolled and assigned to treatment arms based on a stratified sampling scheme. Blood samples will be collected at defined intervals to assess MRD status. Primary endpoints include minimal residual disease (MRD) negativity rate, duration of remission, event-free survival (EFS), and overall survival (OS).

This is a prospective, single-arm phase 2 pilot study to assess the response rate of IDH1 mutated relapsed/refractory acute myeloid leukemia (AML) patients who receive olutasidenib after progressing on venetoclax based regimens. Each cycle will last for 28 days. Patients will receive olutasidenib 150 mg orally twice daily Day 1 through Day 28. After 3 cycles of olutasidenib, azacitidine 75 mg/m2 given on Day 1 through Day 7 may be added at the discretion of the treating investigator if the patient has not achieved a complete remission. Subjects with at least a PR after 6 cycles of treatment will continue treatment as previously described. Subjects without at least a partial response (PR) after 6 cycles of treatment will move to long term follow up.

This is a phase II, open-label, multi-center study evaluating the efficacy and safety of sonrotoclax (SA) in combination with azacitidine (AZA) plus individualized targeted or chemotherapeutic agents in adult participants with newly diagnosed acute myeloid leukemia (AML). Eligible participants will be stratified into different treatment arms based on genetic background (FLT3/IDH1 mutation status) and fitness for intensive chemotherapy. All participants will receive sonrotoclax with dose escalation from 20 mg/day to 320 mg/day, followed by maintenance dosing, which may be temporarily held by the investigator from Day 14 to Day 28 of each 28-day cycle based on the participant's condition, combined with azacitidine 75 mg/m²/day intravenously on Days 1-7. For participants fit for intensive chemotherapy, additional anthracycline (daunorubicin 60 mg/m²/day or idarubicin 10 mg/m²/day on Days 1-3) will be administered. For participants with FLT3 mutations, gilteritinib 80 mg once daily on Days 1-14 will be added; for those with IDH1 mutations, ivosidenib 500 mg once daily on Days 1-28 will be added.