Testing SIROLIMUS in Beta-thalassemia Transfusion Dependent Patients
Condition: Beta-Thalassemia
MeSH terms: Thalassemia; beta-Thalassemia
Study type: Interventional
Phase: Phase 2

Summary: 
      Beta-thalassemias are hereditary blood disorders caused by reduced or absent synthesis of
      hemoglobin beta chains, with variable outcomes ranging from severe anemia to clinically
      asymptomatic individuals. Treatment is symptomatic and thalassemia is a major unmet medical
      need. Survival is increased, even in patients needing transfusions, in comparison with a few
      years ago, but the quality of life is poor for many patients. In some patients, an anomalous
      expression of gamma-globin genes has been observed, with a consequent rise in Fetal
      Hemoglobin levels. The patients displaying a clinical phenotype known as Hereditary
      Persistence of Fetal Hemoglobin (HPFH) exhibit a positive clinical status. To mimick HPFH,
      several compounds able to induce expression of fetal hemoglobins (HbF) have been evaluated.
      Within this framework, sirolimus is particularly interesting as an inducer of HbF. It has
      been used for many years for different indications and the available preclinical evidence
      warrant the start of a clinical development plan in thalassemia. The investigators propose a
      clinical trial in beta-thalassemia patients, designed to evaluate the effect of sirolimus on
      several parameters related to red blood cell status and to the level of HbF in particular, as
      a first step for the full clinical development in this new indication.
    

Detailed description: 
      The general aim of the protocol is to demonstrate the applicability of a personalised and
      precision medicine approach in beta-thalassemia in a clinical trial setting for a repurposed
      drug, namely sirolimus. The presence of high level of Fetal Hemoglobin (HbF) is considered a
      condition predictive of a favourable outcome in thalassemia and its increase induced by
      pharmacological agents is considered a potential way to improve clinical status of the
      patients. In the present trial, in terms of efficacy analysis, the investigators will focus
      their attention on HbF levels.

      Primary objective:

      • To evaluate the suitability of sirolimus for the treatment of beta-thalassemia patients
      within the frame of a comprehensive project aimed to the reduction of their transfusions need
      (consequently ameliorating their quality of life). This goal can be obtained through a
      pharmacologically mediated increased level of HbF, with a prerequisite to be verified, namely
      the correlation between induction of HbF in vitro and in vivo in single patients.

      Secondary objectives:

        -  To assess 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 hematopoietic and immune system of thalassemia
           patients.
    

Intervention name(s): Sirolimus 0.5 mg
Intervention type(s): Drug
Intervention description(s): Daily administration of 1 or more tablets
Intervention MeSH terms: Sirolimus
Intervention model: Single Group Assignment
Intervention model description: Interventional, pilot, single centre, open-label phase II study with sirolimus in patients with transfusion dependent beta-thalassemia
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Fetal hemoglobin; Sirolimus; Red Blood Cells