View clinical trials related to Acute Leukaemia.
Filter by:A novel method has been developed to expand natural (NK) cells and enhance their cytotoxicity against cancer cells while maintaining low killing capacity against non-transformed cells. In this method, donor NK cells are expanded by co-culture with the irradiated K562 cell line modified to express membrane bound IL-15 and 41BB ligand (K562-mb15-41BBL). Expression of these proteins in conjunction with unknown stimuli provided by K562 cells promotes selective growth of NK cells. Then, the expanded NK cell population is depleted of T cells to prevent graft versus host disease (GVHD). Expanded and activated NK cells showed powerful anti-leukemic activity against acute myeloid leukemia (AML) cells in vitro and in animal models of leukemia.Unpublished laboratory results also demonstrated that T-cell acute lymphoblastic leukaemia (T-ALL) is extremely sensitive to the cytotoxicity exerted by the expanded and activated NK cells. The present study represents the translation of the laboratory findings into clinical application. The study proposes to determine the feasibility, safety and efficacy of infusing expanded NK cells into patients who have AML or T-lineage ALL which is resistant to standard therapy as demonstrated by persistent minimal residual disease (MRD). Patients with myelodysplastic syndrome (MDS), who are at high risk to develop AML will also be eligible for the study. In this patient cohort, the study will also investigate the in vivo lifespan and phenotype of the expanded NK cells. The main hypothesis to be tested in this study is that infusion of expanded activated NK cells can produce measurable clinical responses in patients with AML or T-ALL.
The main objective of this project is not only a better understanding of the human leukemic disease but also to find new anti-leukemic or improve existing ones. This study has, the following aims: - To analyze the genetic and epigenetic regulation of the retinoic acid induced cascade which leads to the expression of TRAIL in blood cells of patients with acute leukemia. This study will be complemented by the analysis of global gene expression (DNA chips) and of the DNA methylation state, and by chromatin immunoprecipitation experiences. - To determine the efficiency of inhibitors of enzymes responsible for the modification of chromatin (existing and new developments within the European consortium EPITRON coordinated by Dr Gronemeyer) as inducers of differentiation and / or apoptosis of leukemic blasts. - To explore Ikaros genic and functional abnormalities (genomic deletions, mutations, abnormal transcripts and proteins) in acute leukemia. The aim is to determine if these abnormalities may play a prognosis role.