Beta talassemia trasfusione dipendente MedDRA version: 17.1 Level: PT Classification code 10043391 Term: Thalassaemia beta System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: autologous CD34+ cells transduced with GLOBE LV encoding for B-globin gene
Product Code: NA
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Autologous CD34+ cells tr
Sponsors
OSPEDALE SAN RAFFAELE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Written informed consent • Transfusion-dependent beta-thalassemia (any genotype). Transfusion dependence is defined as receiving = 8 transfusions of blood per year over a minimum of 2 years. • Karnofsky Index or Lansky > 80% • Age = 3 years and 50% and forced expiratory volume in 1 sec (FEV1) and forced expiratory vital capacity (FVC) > 60% predicted (if non cooperative: pulse oximetry > 95 % in room air) ? Serum creatinine =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Use of other investigational agents within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents) • Severe, active viral, bacterial, or fungal infection at eligibility evaluation • Malignant neoplasia (except local skin cancer or cervical intraepithelial neoplasia) or exceptional family history of familial cancer syndromes • Myelodysplasia, cytogenetic alterations associated with neoplasia, or other serious haematological disorder than thalassemia • History of uncontrolled seizures • Other clinical conditions judged non compatible with the procedure and/or the treatment • Positivity for HIV (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA (or negative HCV RNA but on antiviral treatment) and/or Treponema Pallidum or Mycoplasma active infection • Active alcohol or substance abuse within 6 months of the study • Pregnancy or lactation • Previous allogeneic bone marrow transplantation or gene therapy • For paediatric patients only: availability of an HLA-matched donor (sibling or of a suitable 10/10 matched unrelated donor).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the safety and tolerability of autologous CD34+ cell enriched fraction that contains Hematopoietic Stem Cells (HSC) transduced with Lentiviral Vector (LV) encoding the beta-globin gene in pediatric and adult patients with transfusion dependent beta-thalassemia following a reduced toxicity conditioning regimen. 2. To evaluate the efficacy of autologous CD34+ cell enriched fraction that contains Hematopoietic Stem Cells (HSC) transduced with Lentiviral Vector (LV) encoding the beta-globin gene in pediatric and adult patients with transfusion dependent beta-thalassemia following a reduced toxicity conditioning regimen. ;Secondary Objective: NA;Primary end point(s): End point primario: 1) Overall survival E.5.1.1 Tempo/i di rilevazione di questo end point: • 2 years from gene therapy E.5.1 End point primario (ripetere se necessario): 2) Achievement of hematological engraftment defined as: • first day of neutrophil count >500/mm3 • platelets >20,000/mm3 on 3 consecutive blood counts = day +60 from gene therapy. E.5.1.1 Tempo/i di rilevazione di questo end point: • neutrophil count (0-24h) • platelets count = day +60 from gene therapy E.5.1 End point primario (ripetere se necessario): 3) Safety of the administration of autologous HSC transduced with LV-GLOBE measured as: • short-term tolerability; • absence of Replication Competent Lentivirus (RCL); • absence of abnormal clonal proliferation. E.5.1.1 Tempo/i di rilevazione di questo end point: • short-term tolerability (0-24 hours from gene therapy); • absence of Replication Competent Lentivirus (RCL) (0-24 months) • absence of abnormal clonal proliferation (0-24 months). E.5.1 End point primario (ripetere se necessario): 4) Short-term safety and tolerability of the different conditioning regimens. E.5.1.1 Tempo/i di rilevazione di questo end point: • from day -5 to day 100 after ATIMP Injection by clinical and laboratory surveillance E.5.1 End point primario (ripetere se necessario) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): NA;Timepoint(s) of evaluation of this end point: NA | — |
Countries
Italy
Contacts
Public ContactTIGET Clinical Trial Office (TCTO)
OSPEDALE SAN RAFFAELE
Outcome results
None listed