Leukemia, Myeloid, Acute

This study will evaluate whether processing blood stem cell transplants using an investigational device (the CliniMACS system) results in less complications for patients undergoing transplant for treatment of a blood malignancy (cancer) or blood disorder.

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.

This study is for patients who have a type of blood cancer that expresses the protein CD70, which includes acute myeloid leukemia (AML), T-cell leukemia or B-cell leukemia (and the leukemia has come back or has not gone away after standard of care treatment). As there are limited or no remaining standard treatments available to treat this cancer, subjects are being asked to volunteer to be in a gene transfer research study using special immune cells to create a specialized immune cell that will recognize a protein called CD70 that is expressed on the outside surface of the leukemia cells in a subject's body. The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research study combines different ways of fighting disease by using T cells and "arming" them to recognize a specific protein on cancer cells. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. T cells by themselves have been used to treat patients with cancers and have shown promise, but have not been strong enough to cure most patients. T lymphocytes can kill tumor cells but there normally are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person. The protein used in this study is called anti-CD70. It has been developed from human CD27 on normal T cells, since it is the natural binding partner that can connect with CD70. This anti-CD70 protein sticks to leukemia cells when it binds to CD70. CD70 binders have been used to treat people with leukemia. For this study, anti-CD70 has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor or "CAR T cell". The doctors then made another change to cause these T cells to kill any cell that has CD70. This causes the "CAR T cells" to kill blood cancer cells which are confirmed to have CD70. In the laboratory, investigators have found that T cells work better if there are proteins added which stimulate T cells. The anti-CD70 (CD27) protein is unique because it can bind to CD70 on leukemia cells but also stimulates the T cells that express it. Adding the CD27 makes the cells grow better and may help them to last longer in the body, thus giving the cells a better chance of killing the leukemia cells. These CD70 "CAR" T cells are investigational products not approved by the Food and Drug Administration. The purpose of this study is to find a dose of CAR T cells that is safe, to learn what the side effects are and to see whether this therapy might help people with leukemia.

The Registry MDS is an ongoing, observational study that has collected longitudinal data on diagnostics, demographics, clinical parameters, and health Care Interventions (HCI) from patients with MDS and therapy-related acute myeloid leukemia

The safety, tolerability, and antileukemic response of ziftomenib in combination with standard of care treatments for patients with relapsed/refractory acute myeloid leukemia will be examined with the following agents: FLAG-IDA, low-dose cytarabine, and gilteritinib.

The goal of this study is to test an electronic health (eHealth) mindfulness-based music therapy intervention to improve health-related quality of life and reduce symptom burden and disease activity in patients undergoing stem cell transplantation.

The purpose of this research is to see how certain genetic variations relate to side effects and outcomes experienced while receiving treatment with azacitidine and venetoclax.

Acute myeloid leukemia (AML) with FLT3 mutation accounts for 30% of patients and is associated with a poor prognosis. Because of the FLT3 mutation, a tyrosine kinase inhibitor, midostaurin (MIDO), is added to the standard treatment with daunorubicin and cytarabine, from D8 to D21 of induction and of each consolidation cycle, followed by one year of maintenance. Venetoclax (VEN), a BCL2 inhibitor, has revolutionized the management of AML patients ineligible for intensive chemotherapy, in combination with azacitidine or cytarabine. The investigators hypothesize that a four-drug induction regimen (daunorubicin+cytarabine+MIDO+VEN) will increase complete remission (CR) rate without measurable residual disease (MRD) and improve event free survival (EFS), relapse free survival (RFS) and overall survival (OS) of this subgroup of patients with unmet medical need.

The goal of this clinical trial is to learn if Revumenib in combination with Fludarabine and Cytarabine can treat children with NUP98-rearranged relapsed or refractory Acute Myeloid Leukemia. The main question it aims to answer is: What is the Best Overall Response Rate by morphologic response criteria after up to two cycles of revumenib in combination with fludarabine and cytarabine (FLA) chemotherapy? Participants will receive up to two cycles of Revumenib in combination with fludarabine and cytarabine with intrathecal triple therapy. Participant may also receive a stem cell transplant followed by Revumenib monotherapy if it is necessary. Up to 27 children and young adults will be enrolled.

The purpose of this study is to provide a new type of treatment for AML. This treatment combines a new type of stem cell transplant along with treatment using chimeric antigen receptor (CAR) T cells that have been engineered to recognize and attack your AML cells. The first treatment is a modified stem cell transplant, using blood-forming stem cells donated from a healthy donor. From the same donor, we will also make CAR T-cells, which are leukemia fighting cells, which will be given to the patient via an infusion into the vein after the transplanted stem cells have started to grow healthy blood cells. The modification of the stem cell transplant means that the healthy bone marrow cells will be "invisible" to the CAR T-cells that are trying to kill the leukemia cells.

The goal of this clinical research study is to learn if azacitidine combined with Chidamide will help to control the disease in patients with high-risk AML after an allogeneic stem cell transplant. The safety of this combination will also be studied.

This study will evaluate the safety, tolerability, and efficacy of Orca-T in participants undergoing reduced intensity or non-myeloablative allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancies. Orca-T is an allogeneic stem cell and T-cell immunotherapy biologic manufactured for each patient (transplant recipient) from the mobilized peripheral blood of a specific, unique donor. It is composed of purified hematopoietic stem and progenitor cells (HSPCs), purified regulatory T cells (Tregs), and conventional T cells (Tcons).

The goal of this Phase I/II, single arm, prospective, open label, dose escalation trial is to assess safety, feasibility and efficacy of ex vivo expanded autologous T cells genetically modified to express a T cell receptor (TCR) specific for dNPM1 peptides restricted to human leukocyte antigen (HLA) A\*02:01 in patients with relapsed or refractory AML.

A phase 1/2 dose escalation / dose expansion study of Enzomenib (DSP-5336) in patients with acute leukemia.

This retrospective multicentre cohort evaluates the agreement of measurable residual disease (MRD) detection in acute myeloid leukaemia (AML) using two flow-cytometry gating approaches. Manual expert gating is compared with an unsupervised FlowSOM clustering algorithm across post-induction and post-consolidation samples from 50 adults and 10 paediatric patients treated at Bordeaux University Hospital. The primary hypothesis states that unsupervised gating detects MRD ≥ 0.1 % with sensitivity and specificity comparable to manual gating.

Study BH-30236-01 is a first-in-human (FIH), Phase 1/1b, open-label, dose escalation and expansion study in participants with relapsed/refractory acute myelogenous leukemia (R/R AML) or higher-risk myelodysplastic syndrome (HR-MDS). Phase 1, Part 1 Dose Escalation - Monotherapy will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of BH-30236 administered orally. Approximately 50 participants may be enrolled in Phase 1, Part 1 Dose Escalation - Monotherapy. Phase 1, Part 2 Dose Escalation - Combination with Venetoclax will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of BH-30236 administered as a combination therapy with venetoclax. Approximately 48 participants may be enrolled in Phase 1, Part 2 Dose Escalation - Combination with Venetoclax. Phase 1b (Dose Expansion) will follow Phase 1 to further understand the relationships among dose, exposure, toxicity, tolerability, and clinical activity. Up to 72 participants may be enrolled in Phase 1b of the study as a monotherapy or in combination with venetoclax.

The purpose of this study is to evaluate the safety and efficacy of Venetoclax Combining Chidamide and Azacitidine (VCA) in the Treatment of relapsed and/or refractory AML

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.

The main purpose of this study is to identify a safe and potentially effective dose of tuspetinib to be used in future studies in study participants diagnosed with acute myeloid leukemia (AML), myelodysplastic syndromes with increased blasts grade 2 (MDS-IB2), or chronic myelomonocytic leukemia (CMML) that is relapsed or refractory after at least one line of prior therapy, or in study participants with newly diagnosed AML. Tuspetinib will be administered as a single agent or in combination with other drugs (venetoclax or venetoclax plus azacitidine), as specified for each part of the study.

This is a single-arm, single-dose dose-escalation and dose-expansion study.

The purpose of this study is to evaluate the safety and efficacy of Venetoclax Combining Chidamide and Azacitidine (VCA) Followed by D-MAG Regimen on the Treatment of Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Therapy related acute myeloid leukemia and myelodysplasia (t-MN) is a potential late complication of cytotoxic therapy, and it is of particular concern in the treatment of patients with epithelial ovarian carcinoma (EOC) exposed to multiple cycles of platinum-based chemotherapy during the course of their disease. An epidemiological analysis published in 2011 (Gynecologic Oncology) showed that the overall incidence of t-AML is 0.17%, with a median latency to development of leukemia of 4 years (range 0-27 years). Inhibition of PARP is a potential synthetic lethal therapeutic strategy for the treatment of cancers characterized by specific DNA repair defects, such as those that harbor a BRCA1 or BRCA2 (BRCA1/2) mutation and are therefore deficient in homologous recombination repair. In homologous recombination-deficient tumors, PARP inhibition eliminates an alternative DNA repair pathway essential for maintaining viability, leading to tumor cell death. The estimated prevalence of BRCA1/2 mutations in V2 03/06/2021 2 patients with newly diagnosed high-grade serous ovarian cancer is 20-25% and it might be higher in patients with platinum-sensitive, relapsed ovarian cancer. Early studies have shown significant efficacy for PARP inhibitors in patients with germline BRCA1/2 mutations. Our hypothesis is that these patients are carriers of clonal hematopoiesis of indeterminate potential (CHIP) before treatment with PARPi. CHIP refers to the presence of clonal population(s) of hematopoietic cells with somatic mutations in genes associated with hematological malignancies (e.g. DNMT3A, ASXL1, TET2, TP53 and others), in the absence of morphological evidence of disease. The proposed study will address the hypothesis that platinum-based chemotherapy may promote the onset of newly developed mutated clones and clonal selection of hematopoietic stem cells harboring somatic mutations. Moreover, the concomitant presence of germline mutations in cancer predisposing genes might increase the pool of pre-existing hematopoietic clones and/or favor the accumulation of subsequent somatic mutations. In this context, the inhibition of PARP-mediated repair of DNA lesions created by chemo or radiotherapy can further favor t-MN development.

This single-center prospective cohort study aims to evaluate the efficacy and safety of Intensifying treatment with Venetoclax along with intensive chemotherapy in patients with newly diagnosed acute myeloid leukemia (AML) except acute promyelocytic leukemia (non-APL) and exhibiting lower early peripheral blast clearance rate (EPBCR) after standard Intensive Induction therapy (3+7 regimen).

This clinical trial aims to investigate the safety, optimal dosage, and effectiveness of autologous tumor-specific T cells, known as Hema-NeoTIL0 in treating relapsed/refractory B-ALL/AML.

ERASE is part of the MyeloMATCH initiative, Young Adult Basket and is a Tier 2 study. The study is comparing the use of Cytarabine to Cytarabine and Venetoclax, Daunorubicin/Cytarabine Liposome and Venetoclax, and Azacitidine and Venetoclax.