Clinical trials

The purpose of this study is to test the safety and efficacy of iC9-GD2-CAR T-cells, a third generation (4.1BB-CD28) CAR T cell treatment targeting GD2 in paediatric or young adult patients affected by relapsed/refractory malignant central nervous system (CNS) tumors. In order to improve the safety of the approach, the suicide gene inducible Caspase 9 (iC9) has been included.

This is a pilot, prospective, non-profit, multicenter, uncontrolled, open-label study to evaluate the safety and feasibility of FMT in patients aged between 3 months and 25 years suffering from acute intestinal GVHD resistant to conventional steroid therapy. Eligible patients will receive 1-3 FMT via naso-jejunal tube or endoscopy.

Current therapeutic strategies for high-risk or relapsed ALL patients often involve intensive treatments, including allogeneic hematopoietic stem cell transplantation (HSCT). HSCT remains a cornerstone of therapy, offering curative potential; however, it is associated with considerable risks, including non-relapse mortality (NRM), significant morbidity, and long-term complications that continue to be major concerns. In response to these challenges, the FORUM consortium has made substantial progress in improving outcomes for children with ALL undergoing HSCT. The consortium focuses on reducing life-threatening and lifelong complications, ultimately aiming to enhance quality of life for these high-risk patients. Building on the robust evidence generated by FORUM1, the FORUM2 study has been designed to further optimize the role of HSCT in ALL across all age groups and donor settings within a harmonized and internationally coordinated framework. The FORUM2 study introduces a master protocol structure that encompasses multiple hypothesis-driven substudies, each addressing a specific determinant of HSCT outcomes. This design enables simultaneous or sequential evaluation of novel strategies while ensuring uniform governance, endpoint definitions, and data-quality standards. The overarching objective is to refine the role of HSCT in ALL by reducing treatment-related toxicity while preserving the essential graft-versus-leukemia effect.

This is a phase I, open label study to evaluate the safety, identify the recommended dose (RD) and obtain preliminar evidence of the efficacy of allogeneic, CD19-directed Chimeric Antigen Receptor T (alloCAR-T) cells in pediatric and young adults patients with relapsed/refractory B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL).

The main purpose of this study is to evaluate the safety, to establish the recommended dose, and to evaluate the antitumor effect of CD7-CART01 in pediatric patients with relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LL).

The RESILIENT project is a clinical trial investigating leptin sensitivity in both children and adults with overweight or obesity. The study examines the additive effects of Cognitive Training (CT) and Social Training (ST) on leptin sensitivity, compared to stand-alone Intensive Health Behaviour Treatment (IHBT), which includes diet and Physical Activity (PA). The intervention will last for 8 weeks, followed by a 12-week washout period. A multilevel assessment will be conducted, evaluating in vivo leptin sensitivity (through the ratio of leptin levels to caloric intake) as well as ex vivo molecular analysis of leptin signaling in Peripheral Blood Mononuclear Cells (PBMCs). Additionally, clinical, psychological, cognitive, and physiological assessments will be performed to assess the efficacy of each intervention. By investigating leptin resistance as a potential molecular bridge between metabolic dysregulation and cognitive dysfunctions, this study may contribute to the development of more effective, long-term treatments for obesity and overweight. Additionally, in vivo investigation of leptin sensitivity may be particularly important for providing evidence of the metabolic and cognitive effects necessary for developing novel anti-obesity treatments.

Fragile X Syndrome (FXS) is a rare genetic syndrome, caused by a mutation in the FMR1 gene located on the X chromosome. It is considered the leading hereditary cause of intellectual disability (ID) and the primary cause of Autism Spectrum Disorder (ASD) due to a single gene-mutation. Many individuals with FXS exhibit symptoms overlapping with those of ASD, including difficulties in social-communication skills, challenges in peer relationships, restricted and repetitive behaviors/interests and deficits in adaptive functioning. Both in ASD and FXS, individuals with greater deficits in executive functions, socio-pragmatic, and socio-relational skills also demonstrate lower adaptive functioning and, consequently, reduced autonomy/independence throughout the life course and greater severity of the disorder. Among empirically validated treatments recommended by National and International Guidelines for the treatment of ASD, cognitive-behavioral and psychosocial interventions have been shown to improve some aspects of ASD, such as core symptoms, emotional-behavioral disturbances, adaptive skills, and quality of life. Currently, it appears that cognitive-behavioral therapies, which include psychoeducation programs, are particularly appropriate for ASD, with greater efficacy for group interventions compared to individual ones. Regarding FXS, despite the well-established knowledge of the cognitive-behavioral phenotype and the clear need for scientifically validated programs, research on intervention strategies remains quite limited. Considering the similarities between ASD and FXS and the need for standardized interventions, the present research project aims to conduct an RCT to evaluate the feasibility of Cooperative Group Therapy (CGT) in two different groups of adolescents with ASD and FXS. The decision to target the intervention to adolescents is due to the few clinical studies on this age group, which is a crucial target since, in FXS, there is often a plateau or reversal of intellectual and adaptive development after the age of 10, and in adolescents with ASD, the development and complexity of social, pragmatic skills, and executive functions are crucial for good adaptive functioning and a basic quality of life. Te main hypothesis is that CGT could contribute to the reduction of severity illness and in the enhancement of socio-communicative skills.

Repetitive behaviors (RBs) are a prevalent feature of Autism Spectrum Disorder (ASD). There are two groups of RBs: lower-order (e.g. motor stereotypies) and higher-order RBs (e.g. restricted interests), linked to sensory-motor and the associative loops, respectively. To date, treatment options for RBs are very limited. High-definition transcranial direct current stimulation (HD-tDCS) may be effective in reducing the impact of RBs in children with ASD by targeting the associated brain alterations. Moreover, the high focality of HD-tDCS will help the investigators to disentangle the relative contribution of different brain loops (namely, sensory-motor and the associative loops) into RBs subtypes. The investigators will also study the electrophysiological patterns associated to behavioral changes after the application of HD-tDCS.

The present study grounds on the absence of evidence-based treatment in individuals with developmental dyslexia (DD). At this topic, the present study will explore the potential effect of transcranial direct current stimulation (tDCS) over left hemispheric direct Lateral Geniculate Nucleus (LGN)-V5/MT pathway, cerebral areas usually disrupted in individuals with DD. The investigators hypothesized that active tDCS over V5/MT will boost reading skills in children and adolescents with DD. On the contrary, sham (placebo condition) tDCS over V5/MT or active (control condition) tDCS over V1 will not have significant effect in improving reading skills. Further, both active and sham tDCS will be safe and well tolerated.