Testing SIROLIMUS in Beta-thalassemia Transfusion Dependent Patients (THALA-RAP)
Status:
Recruiting
Trial end date:
2022-04-30
Target enrollment:
Participant gender:
Summary
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.