Testing SIROLIMUS in Beta-thalassemia Transfusion Dependent Patients (SIRTHALACLIN)
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|ClinicalTrials.gov Identifier: NCT03877809|
Recruitment Status : Active, not recruiting
First Posted : March 18, 2019
Last Update Posted : December 1, 2020
|Condition or disease||Intervention/treatment||Phase|
|Beta-Thalassemia||Drug: Sirolimus 0.5 mg||Phase 2|
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.
• 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|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)|
|Official Title:||A Personalized Medicine Approach for Beta-thalassemia Transfusion Dependent Patients: Testing SIROLIMUS in a First Pilot Clinical Trial|
|Actual Study Start Date :||June 27, 2019|
|Estimated Primary Completion Date :||April 30, 2021|
|Estimated Study Completion Date :||October 31, 2021|
Experimental: Open label trial
Sirolimus 0.5 mg tablets
Drug: Sirolimus 0.5 mg
Daily administration of 1 or more tablets
- Change from baseline of fetal hemoglobin level [ Time Frame: 360 days ]Fetal hemoglobin level in peripheral blood at day 360 compared to day 0, assessed through high pressure liquid chromatography (HPLC)
- Change from baseline of fetal hemoglobin level [ Time Frame: 180 days ]Fetal hemoglobin level in peripheral blood at days 90 and 180 compared to day 0, assessed through HPLC
- Change from baseline of γ-globin expression [ Time Frame: 360 days ]Level of induction of the γ-globin expression at day 90, 180 and 360 compared to day 0
- Change from baseline of biomarkers for erythropoiesis [ Time Frame: 360 days ]- - Evaluation of the biomarkers for erythropoiesis level at day 180 and 360 compared to baseline. Biomarkers will include: Reticulocytes count, Nucleated red blood cells count
- Change from baseline of biomarkers for erythropoiesis [ Time Frame: 360 days ]- - Evaluation of the biomarkers for erythropoiesis level at day 180 and 360 compared to baseline. Biomarkers will include: erythropoietin level, serum transferrin receptor level.
- Change from baseline of biomarkers for haemolysis [ Time Frame: 360 days ]- Evaluation of the biomarkers for haemolysis level at day 180 and 360 compared to baseline. Biomarkers will include: serum bilirubin level
- Change from baseline of biomarkers for haemolysis [ Time Frame: 360 days ]- Evaluation of the biomarkers for haemolysis level at day 180 and 360 compared to baseline. Biomarkers will include: serum lactate dehydrogenase (LDH) level
- Change from baseline of tranfusion needs [ Time Frame: 360 days ]- Measurement of the total blood quantity (in mL) transfused and recording of the number of transfusions done in a semester (day -360 to -180, day -180 to 0, day 0 to 180, day 180 to 360)
- Change from baseline of Iron status [ Time Frame: 360 days ]
- Evaluation of the intake of iron chelators at days 180 and 360 compared to baseline
- Evaluation of serum ferritin level at day 90, 180 and 360 in comparison with day 0
- Change from baseline of Immune function [ Time Frame: 360 days ]
- Peripheral blood immunophenotype-Lymphocyte subsets at day 90 and 360 compared to day 0
- Quantitative analysis of ImmunoglobulinG/ImmunoglobulinA/ImunoglobulinM at day 90 and 360 compared to day 0
- Change from baseline of Quality of Life [ Time Frame: 360 days ]Evaluation of the patient quality of life at 6 and 12 months compared to baseline through Transfusion-dependent Quality of Life questionnaire (TranQol), measuring specifically the quality of life in patients with thalassemia. The TranQol is a disease-specific Quality of Life measure that has been shown to be valid and reliable (Klaassen et al, British Journal of Haematology, 2014, 164, 431-437). On a total scale of 0-100, higher values always represent a better outcome. The questions are grouped into four domains: physical health, emotional health, family functioning, and school and career functioning. The adult self-report questionnaires include a fifth category on sexual activity which is only one item. Subscales are summed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03877809
|Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology|
|Ferrara, Italy, 44121|
|Department of Growth and Reproduction Azienda Ospedaliero-Universitaria S.Anna|
|Ferrara, Italy, 44124|