A personalized medicine approach for beta-thalassemia transfusion dependent patients: testing SIROLIMUS in a first pilot clinical trial.

Phase 1

• Conditions: beta-thalassemic patients; MedDRA version: 20.0Level: PTClassification code 10043391Term: Thalassaemia betaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Not possible to specify

• Registration Number: EUCTR2018-001942-33-IT
• Lead Sponsor: Rare Partners s.r.l. Impresa Sociale

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-08-03
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1.Responsive to the in vitro (ErPCs) treatment with Sirolimus according to laboratory specific definition (= 20% increase of HbF in comparison with samples not treated with Sirolimus)
2.AST or ALT < 3x ULN (Upper Limit of Normal)
3.Documented Platelet count >150.000/ul
4.Fertile women using an adequate system of contraception
5.Patients willing to follow all the study requirements and perform all the study visits and to cooperate with the investigator
6.Selection criteria must still be fulfilled at the time of the inclusion visit
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Uncontrolled hypertension defined as systolic pressure (PA) = 140 mm Hg or diastolic pressure = 90 mm Hg.
2.Class 3 or higher heart failure (New York Heart Association, NYHA).
3.QTc> 450 msec on selection ECG.
4.White blood cell [WBC] count <3000 cells per µL and/or Granulocytes <1500/mm3
5.Total cholesterol > 240 mg/dl
6.Triglycerides > 200 mg/dl
7.Proteinuria with urinary protein >1g/24 hrs;
8.Any active infection requiring parenteral antibiotic therapy within 28 days prior to inclusion or oral antibiotics within 14 days prior to inclusion;
9.Enrolment into one other drug or device trial since selection;
10.Major surgery (including splenectomy) performed after the study selection visit .
11.Ongoing treatment with drugs and agents that could increase the concentration of Sirolimus in the blood including: ciclosporin, bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, protease inhibitors (eg for HIV and hepatitis C which require pharmacological treatment with ritonavir, indinavir, boceprevir and telaprevir), metoclopramide, nicardipine, troleandomycin, verapamil.
12.Ongoing treatment with drugs and agents that could reduce the concentration of Sirolimus including carbamazepine, phenobarbital, phenytoin, rifapentine, St. John's wort (Hypericum perforatum).
13.Cytotoxic agents, systemic corticosteroids, immunosuppressants or anticoagulant therapy such as warfarin or heparin within 28 days before inclusion (prophylactic aspirin up to 100 mg / day is allowed);
14.Macrolidic antibiotics (clarithromycin), ACE inhibitors.
15.Pregnant or lactating women.
16.Occurrence of an event which leads to the appearance of a non-selection criteria

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main 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 Objective: -To assess safety of sirolimus and correlation between administered dose and blood levels in beta-thalassemia patients,<br>-To assess the influence of sirolimus on transfusion regimen<br>-To assess the effect of sirolimus on hematopoietic and immune system of thalassemia patients.<br>;Primary end point(s): HbF level in peripheral blood at day 360 compared to day 0, assessed through HPLC;Timepoint(s) of evaluation of this end point: for all study period