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56 active trials for Acute Leukemia

A Study to Assess a Physical Activity Program in Children, Adolescents and Young Adults Requiring Hematopoietic Stem Cell Allografts

To date, allogeneic haematopoietic stem cell transplantation (aHSCT) is the only curative treatment for many paediatric and young adult haematological pathologies (acute leukaemia, myelodysplastic syndromes, haemoglobinopathies, bone marrow aplasia, severe combined immunodeficiency). Despite the major therapeutic progress made over the last 50 years, particularly in terms of supportive care, post-transplant morbidity and mortality remains high. Infectious complications, whose incidence varies between 30 and 60%, are the first cause of mortality in the immediate post-transplant period. In order to protect the patient from the occurrence of severe infectious episodes, aHSCTmust be performed in a highly protected environment (positive pressure chambers). This has implications for the experience and impact of hospitalization on the patient and family. This is particularly true in paediatrics, whether in children, adolescents or young adults, where it is not only the patient's quality of life that is at stake, but also their emotional and psychomotor development. In these patients, prolonged hospitalization (at least 6 weeks) in a sterile room will be responsible for physical deconditioning accompanied by a decrease in muscle mass, itself concomitant with undernutrition, and an increase in sedentary lifestyle. This prolonged hospitalisation in a sterile room, associated with myeloablative treatments, is therefore the cause of social isolation of patients, but it is also often synonymous with physical inactivity leading to a rapid decrease in physical condition, quality of life and an increase in fatigue. Today, the benefits of physical activity (PA) during and after cancer treatment have been widely demonstrated. The objective is to evaluate the feasibility of an adapted physical activity program during the isolation phase for achieving aHSCT in children, adolescents and young adults. This is a prospective, interventional, monocentric cohort study conducted at the Institute of Paediatric Haematology and Oncology in Lyon. The intervention will take place during the isolation phase and consists of an adapted physical activity (APA) program defined at inclusion, integrating supervised sessions with an APA teacher, as well as autonomous sessions. The program is individualized according to age, aerobic capacity, and PA preferences. Sessions are also tailored to the biological, psychological, and social parameters of patients. The total duration of the intervention is 3 months. To date, no PA studies have been performed in patients under 21 years of age requiring aGCSH during the sterile isolation phase. EVAADE will therefore be the first study in this population to offer an innovative procedure with a connected device.

Start: December 2018
Action of the Vidaza on the Atrial Fibrillation

Genomic studies on atrial fibrillation patients have identified polymorphisms in regions surrounding the PITX2 gene, suggesting it could be the locus responsible for atrial fibrillation. The PITX2 gene is essential for establishing the asymmetry between systemic and pulmonary blood flow, which is absolutely required for proper heart functions. In addition, PITX2 is required for the development the atrium myocardium. Investigators have performed transcriptomic analysis on left atrium tissues from atrial fibrillation patients and identify genes whose expression is altered in atrial fibrillation. Among affected genes, PITX2 expression is strongly decreased in the left atrium of atrial fibrillation patients. Moreover, investigators observed that the PITX2 promoter region is hypermethylated in atrial fibrillation patients. Interestingly, DNA methylation is a key actor of gene expression and directly regulates RNA transcription either by directly modulating transcription factor (TF) binding to gene promoters or by modifying local chromatin structures, therefore limiting access of TFs to DNA. These epigenetic modifications are reversible and therefore represent an interesting therapeutic target. Hence, many compounds that inhibit DNA methyl-transferase are currently tested in different disease models. Recently-designed hypomethylating molecules are available, such as the 5'azacytidine (Vidaza®, Celgen Inc.) or the 5-aza-2'-deoxycytidine (Decitabine) (Dacogen®, Janssen Cilag). Investigators have performed preliminary studies on the effect of Decitabine on DNA methylation and proper cardiac function recovering in a SHR model. Results indicate that the chronic delivery of Decitabine improves the arrhythmia profile by reducing tachyarrhythmia, fibrosis, as well as the oxidative stress in SHR left atrium submitted Acute Leukemia is a rare pathology with an incidence of 4 per 100,000 in France. Azacytidine, which is closely related to Decitabine, is commonly used for treating Acute Leukemia and possesses anti-neoplastic effect through multiple mechanisms, including direct cytotoxicity of blood cancer cells and DNA hypomethylation. The goal of this study is to evaluate the effects of azacytidine on arrhythmia and left atrium fibrosis as well, which are the two mains phenotypic manifestation of atrial fibrillation in humans. Investigators hypothesize that azacytidine decreases PITX2 promoter methylation and increases PITX2 expression. Hence, investigators expect to ameliorate the duration of atrium action potential and to observe a decrease of atrium fibrosis.

Start: December 2018