View clinical trials related to Leukemia, Myeloid.
Filter by:This is a non-randomised, open-label phase I study of an investigational medicinal product (IMP) consisting of a HLA-A*02:01 restricted HA-1H T cell receptor transduced T cell (MDG1021) immunotherapy for relapsed or persistent hematologic malignancies after allogeneic hematopoietic stem cell transplantation. The aim of the study is to determine the recommended phase II dose of MDG1021.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for numerous malignant hematologic diseases. Despite recent advances in the field, relapse rates are still high and the first cause of death. The identification of new relevant therapeutic targets is therefore urgently needed. Human endogenous retroviruses (HERVs) are accounting for 8% of the human genome. While silenced at the steady state (mainly by methylation mechanisms), HERVs reactivations have been described in different conditions such as auto-immune diseases or cancer, leading to an innate and adaptive immune response. Several questions are raised in the field of hematology where few data are available, and the exact role of HERVs in these diseases is still to define. Our team is currently working on the role of HERVs in different types of cancer. We developed a bioinformatics approach to identify overexpressed HERVs from RNAseq data. We also developed in vitro assays to assess the immunogenicity of different peptides from HERVs open reading frames and showed that several epitopes shared among different HERVs can induce a specific CD8+ T cell response. More recently, we have analyzed 151 acute myeloid leukemia (AML) RNAseq data from TCGA and identified multiple overexpressed HERVs in this disease. Immunogenicity test are currently ongoing with patient's blood at diagnosis. The main objective of this part of our project is to analyze the establishment of a HERVs-specific CD8+ T cell response participating in graft-versus-leukemia effect after HSCT for AML patients. Secondary objectives are to analyze relations between this response and different clinical factors such as the onset of GVHD or relapse. Peripheral blood mononuclear cells (PBMCs) from AML patients will be extracted and frozen at different time point: diagnosis, complete remission (pre-HSCT) and after HSCT (M3, M6 and M12). This prospective protocol is currently ongoing at the Centre Hospitalier Lyon Sud, with around 30 samples already available. After having selected relevant HERVs, specific dextramers identified by DNA barcode will be synthesized. These dextramers allowing the identification of specific T cell responses directed against up to 1000 epitopes, we will be able to screen specific T cells directed against HERVs overexpressed in AML for most common HLA. Dextramer staining will be performed on PBMCs after thawing. Positive cells will be sorted by flow cytometry and DNA will be expanded by PCR before performing sequencing, allowing the identification of specific sequences by its unique DNA barcode. The analyze of HERVs-specific CD8+ T cell responses after HSCT will allow us to better define HERVs role in the onset of graft-versus-leukemia effect. A specific T cell response without GvHD will define the relevance of such peptides as tumor specific antigens.
There are no strategies developed post-stem cell transplant (SCT) for patients who receive allogenic SCT with a significant amount of blasts prior SCT. Novel strategies to treat relapsed AML/MDS and to reduce the incidence of relapse after allogeneic SCT are needed. This study is being done in patients with high-risk MDS or AML who undergo an allogeneic SCT. The study will have two arms, participants who receive an HLA-matched unrelated donor SCT (Arm A) or HLA- haploidentical SCT (Arm B). Following myeloablative conditioning (MAC), GVHD prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus and mycophenolate mofetil will be given per standard of care. At 40-60 days post SCT, If the patient has not had any evidence of Grade II-IV acute graft-versus-host-disease (aGVHD), Nivolumab will be given intravenously every 2 weeks for 4 cycles of consolidation or treatment with Nivolumab. Dose-escalation of Nivolumab will follow the standard 3+3 design where a maximum of three dose levels will be evaluated, with a maximum of 18 patients treated with nivolumab per arm. As the maximum tolerated dose (MTD) of Nivolumab may differ between Arm A and Arm B, dose escalation of nivolumab in each arm will be followed separately following allogeneic SCT. Immunosuppression with tacrolimus will be continued during the cycles of PD-1 blockade to provide a moderate level of GVHD prophylaxis during consolidation or treatment with nivolumab.
This phase 2 clinical trial investigates the effectiveness of cytokine-induced memory-like natural killer (CIML NK) cells in combination with FLAG chemotherapy as a treatment for refractory or relapsed AML. Previous studies in adults with AML sowed successful induction of remission and a previous phase 1 study demonstrated that CIML NK cells can be used safely in pediatric patients. This phase 2 study uses FLAG chemotherapy to lower leukemic burden and suppress the recipient's immune system to provide an optimal environment for CIML NK cell expansion and anti-leukemic activity.
The investigators want to compare the global response rate of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) after six months of treatment with 5-azacitidine on two different doses. First group of 50 mg/m2 for 10 days each 28 days versus 75 mg/m2 for 7 days on 28 days cycles.
This is a Phase II trial testing disease-specific myeloablative conditioning regimens for preparatory cytoreduction of patients receiving allogeneic HLA-compatible related or unrelated transplants of GCSF-mobilized peripheral blood stem cells (PBSC) depleted of T-cells by positive selection of CD34+ progenitor cells using the CliniMACS system. The CliniMACS Fractionation system is a method that positively selects CD34+ progenitor cells from PBSC by immunoadsorption of cells binding on anti CD34 monoclonal antibody to paramagnetic beads, which can then be isolated by passage through a magnetized column and released by agitation of beads. Two conditioning regimens have been used successfully with an alternative similar system, isolex, which is no longer being manufactured.
Among patients with a diagnosis of AML who received non-intensive chemotherapy: - Describe patient demographic and clinical characteristics - Describe treatment patterns - Describe effectiveness outcomes - Evaluate tumor response
This is a Phase I, open-label, dose escalation study of UCART123 administered intravenously to patients with newly diagnosed CD123 positive adverse genetic risk acute myeloid leukaemia (AML) defined in the ELN adverse genetic risk group (2017). The purpose of this study is to evaluate the safety and clinical activity of multiple infusions of UCART123 and to determine the Maximum Tolerated Dose (MTD).
This is a Phase 2, randomized, open-label, multicenter study to evaluate the safety and efficacy of ficlatuzumab in combination with high-dose cytarabine (HiDAC) and HiDAC alone in subjects with relapsed or refractory acute myeloid leukemia.
This phase Ib/II trial studies the side effects and best dose of FT-2102 when given together with ASTX727 in treating patients with IDH1-mutated myelodysplastic syndrome or acute myeloid leukemia that has come back (recurrent) or does not respond to treatment (refractory). ASTX727 is an oral deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor. DNA methylation is necessary for cell differentiation and development. Changes to the methylation profile can lead to DNA instability which can cause diseases like cancer. DNMT inhibitors target and inhibit these changes. FT-2102 is an isocitrate dehydrogenase 1 (IDH1) inhibitor. IDH1 is a type of protein involved in metabolism, or the process of providing the body's cells with energy. FT-2102 may stop the abnormal IDH1 protein and may reduce 2-HG levels in diseased cells to levels found in normal cells. Giving ASTX727 and FT-2102 may work better in treating patients with myelodysplastic syndrome or acute myeloid leukemia compared to ASTX727 and FT-2102 alone.