Beta-Thalassemia Clinical Trial
Official title:
A Personalized Medicine Approach for Beta-thalassemia Transfusion Dependent Patients: Testing SIROLIMUS in a First Pilot Clinical Trial
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.
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. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00069862 -
Iron Balance Study of DFO and GT56-252 in Patients With Transfusional Iron Overload Secondary to Beta-Thalassemia
|
Phase 1/Phase 2 | |
| Completed |
NCT00733811 -
Efficacy Study of the Use of Sequential DFP-DFO Versus DFP
|
Phase 4 | |
| Completed |
NCT05506358 -
Evaluation of Low-cost Techniques for Detecting Sickle Cell Disease and β-thalassemia in Nepal and Canada
|
N/A | |
| Withdrawn |
NCT04938635 -
Efficacy and Safety Study of Multiple Doses of VIT-2763 in Adults With Transfusion-dependent Beta-thalassemia
|
Phase 2 | |
| Active, not recruiting |
NCT03655678 -
A Safety and Efficacy Study Evaluating CTX001 in Subjects With Transfusion-Dependent β-Thalassemia
|
Phase 2/Phase 3 | |
| Completed |
NCT06239389 -
Comparison Of Efficacy And Safety Of Thalidomide Vs Hydroxyurea In Thalassemia Patients: A Single-Centre Pilot Study.
|
Phase 2 | |
| Recruiting |
NCT05635266 -
Tissue Repository Providing Annotated Biospecimens for Approved Investigator-directed Biomedical Research Initiatives
|
||
| Completed |
NCT03271541 -
A Study of Bitopertin (RO4917838) in Adults With Non-Transfusion-Dependent (NTD) Beta-Thalassemia
|
Phase 2 | |
| Terminated |
NCT02274233 -
Safety and Pharmacokinetic Study of Escalating Doses of SP-420, an Iron Chelator, in Patients With β-Thalassemia
|
Phase 1 | |
| Completed |
NCT01206075 -
Evaluating the Safety and Effectiveness of Mozobil Mobilization in Adults With Beta-Thalassemia Major
|
N/A | |
| Recruiting |
NCT05567458 -
A Study to Evaluate Luspatercept (ACE-536) in Chinese Participants Who Require Regular Red Blood Cell Transfusions Due to Beta (β)-Thalassemia.
|
Phase 2 | |
| Enrolling by invitation |
NCT03655223 -
Early Check: Expanded Screening in Newborns
|
||
| Completed |
NCT03961828 -
Hyalornic Acid Level in β-Thalassemic Children Treated for Hepatitis C Virus
|
Phase 4 | |
| Recruiting |
NCT06065189 -
Base-edited Autologous Hematopoietic Stem Cell Transplantation in Treating Patients With β-thalassemia Major
|
Early Phase 1 | |
| Recruiting |
NCT04143724 -
Study of Safety & PK of Luspatercept (ACE-536) in Pediatric Participants With Beta (β)-Thalassemia
|
Phase 2 | |
| Terminated |
NCT03381833 -
A Study With LJPC-401 for the Treatment of Myocardial Iron Overload in Patients With Transfusion-Dependent Beta Thalassemia
|
Phase 2 | |
| Completed |
NCT02268409 -
ACE-536 Extension Study - Beta Thalassemia
|
Phase 2 | |
| Not yet recruiting |
NCT01996683 -
Efficacy and Safety of Efficacy and Safety of Continued Iron Chelation Therapy In Poly-transfused Thalassemia Patients With Low Serum Ferritin (< 500 ng/ml)
|
N/A | |
| Active, not recruiting |
NCT01016093 -
Zoledronic Acid for the Prevention of Bone Loss Post-bone Marrow Transplantation for Thalassemia Major Patients
|
Phase 2/Phase 3 | |
| Completed |
NCT01039636 -
Safety and Pharmacokinetic Study of Escalating Multiple Doses of an Iron Chelator in Patients With Iron Overload
|
Phase 1 |