Beta-Thalassemia Clinical Trial
Official title:
Treatment of Beta-thalassemia Patients With Rapamycin (Sirolimus): From Pre-clinical Research to a Clinical Trial" - "Trattamento di Pazienti Con Beta-talassemia Con Rapamicina (Sirolimus): Dalla Ricerca Pre-clinica ad Uno Studio Clinico
In β-thalassaemia and Sickle Cell Disease (SCD), a significant production of fetal haemoglobin (HbF) may reduce the severity of clinical course and reactivation of γ-globin gene expression in adulthood. HbF induction is one of the best strategies to ameliorate the characteristic symptoms of these diseases. Hydroxyurea (HU) is the only medication, approved by the US Food and Drug Administration, inducing HbF. However, treatments with HU induce sufficient HbF levels in only half of the patients, and side effects including leukopenia and neutropenia are frequently reported. Therefore, novel therapeutic inducers must be identified to develop a personalized treatment in β-thalassaemia and sickle cell anaemia. The availability of new treatments depends on drugs already approved for other indications, and on pharmacokinetics and pharmacovigilance already assessed. Rapamycin (as Sirolimus) is an immunosuppressant agent, approved by the FDA for acute rejection prevention in renal transplant recipients. The ability of this drug to induce γ-globin gene expression in erythroleukemia cell line and erythroid precursors cells (ErPCs) in ß-thalassaemia patients is already known. A clinical investigation on the effects of sirolimus in ß-Thalassaemia aims to evaluate several parameters related to red blood cell status and HbF levels and is a first step for the full clinical development in this new indication.
The general aim of this protocol is to demonstrate the applicability of a personalised and precision medicine approach in beta-thalassaemia; the clinical trial setting repurposes a drug, namely sirolimus. The presence of high Fetal Hemoglobin (HbF) levels is considered a condition predictive of a favourable outcome in thalassaemia. Its increase induced by pharmacological agents is considered a potential way to improve the clinical status of the patients. In terms of efficacy analysis, the investigators will focus their attention on HbF levels. Primary objective: • The suitability evaluation of sirolimus for the treatment of beta-thalassemia patients within the frame of a comprehensive project aimed at the reduction of their transfusions need, with consequent amelioration of their quality of life. The purpose can be achieved through increasing of HbF levels pharmacologically mediated, with verification of a prerequisite, namely the correlation between the induction of HbF in vitro and in vivo in single patients. Secondary objectives: - To assess the safety of sirolimus and correlation between administered dose and blood levels in beta-thalassemia patients - To assess the influence of sirolimus on transfusion regimen - To assess the effect of sirolimus on the hematopoietic and immune system of thalassemia patients. ;
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