HAEMATOPOIETIC STEM CELL GENE THERAPY

A PHASE I/II CLINICAL TRIAL OF HAEMATOPOIETIC STEM CELL GENE THERAPY FOR THE WISKOTT-ALDRICH SYNDROME - TIGET-WAS

Status

Active, not recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2009-017346-32-IT

Enrollment

Registered

2010-04-26

Start date

2010-03-15

Completion date

Unknown

Last updated

2024-03-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Wiskott-Aldrich Syndrom MedDRA version: 20.0 Level: PT Classification code 10061598 Term: Immunodeficiency System Organ Class: 10021428 - Immune system disorders

Interventions

Trade Name: FLUDARABINA TEVA - 25 MG/ML CONCENTRATO PER SOLUZIONE INIETTABILE O PER INFUSIONE 1 FLACONCINO DI VETRO DA 2 ML Product Name: na Product Code: [na] Pharmaceutical Form: Solution for infusi

Eligibility

Sex/Gender

Male

Inclusion criteria

Inclusion criteria: 1) Diagnosis of WAS defined by genetic mutation and at least one of the following criteria: -severe WAS mutation -absent WASP expression -severe clinical score (Zhu clinical score >= 3); 2) No HLA-identical sibling donor; and 3.1) Negative search for a matched unrelated donor (10/10) or an adequate unrelated cord blood donor (5-6/6) within 4-6 months; or 3.2) Patients of > 5 years of age who are not candidate to unrelated allogeneic transplant based on clinical conditions and 4) Parental/guardian/patient signed informed consent Are the trial subjects under 18? yes 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 1 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: Patients who meet any of the following criteria will be excluded from study admission: 1) Patients positive for HIV-infection 2) Patients affected by neoplasia 3) Patients with cytogenetic alterations typical of MDS/AML 4) Patients with end-organ functions or any other severe disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study 5) Patients who underwent an allogeneic haematopoietic stem cell transplantation in the previous 6 months 6) Patients who underwent an allogeneic haematopoietic stem cell transplantation with evidence of residual cells of donor origin

Design outcomes

Primary

Measure	Time frame
Primary end point(s): Primary safety endpoints 1) Conditioning regimen-related safety, consisting in the absence of prolonged aplasia and surveillance of non haematological regimen related toxicity (for clinical features NCI >2, for metabolic/laboratory NCI >3) 2) Safety of lentivirus gene transfer into HSC -short-term safety and tolerability of lentiviral-transduced cell infusion -long-term safety of lentiviral-transduced cell infusion (absence of Replication competent lentivirus (RCL) and abnormal clonal proliferation). Primary efficacy endpoints 1) overall survival 2) Sustained engraftment of genetically corrected haematopoietic stem cells in peripheral blood and/or in bone marrow 3) Expression of vector-derived WASP 4) Improved T-cell functions 5) Antigen-specific responses to vaccination 6) Improved platelet count;Timepoint(s) of evaluation of this end point: -Ematologic recovery: + 60 days-Safety to quickly treated cell infusion: absence of adverse reactions within 48 hours-long term Safety of infusion treated cells: RCL at baseline, after 1, 3, 6, 12 months and 24 months.;Main Objective: Primary objectives: 1) To evaluate the safety of the administration of autologous CD34+ cells transduced with a lentiviral vector containing the WASP gene in patients with WAS, after a reduced intensity conditioning regimen. 2) To evaluate the long-term engraftment of WASP-expressing transduced cells. 3) To evaluate the efficacy of gene therapy assessed as: 3.1 Improvement of the patient s immune function (specially T cell function and antigen-specific responses to vaccinations). 3.2 Improvement of thrombocytopenia.;Secondary Objective: To evaluate the efficacy of gene therapy in improving the patients s clinical condition, assessed by a reduction in frequency of severe infections, and bleeding episodes and reduction of auto-immunity phenomena and eczema.	—

Measure

Time frame

Primary end point(s): Primary safety endpoints 1) Conditioning regimen-related safety, consisting in the absence of prolonged aplasia and surveillance of non haematological regimen related toxicity (for clinical features NCI >2, for metabolic/laboratory NCI >3) 2) Safety of lentivirus gene transfer into HSC -short-term safety and tolerability of lentiviral-transduced cell infusion -long-term safety of lentiviral-transduced cell infusion (absence of Replication competent lentivirus (RCL) and abnormal clonal proliferation). Primary efficacy endpoints 1) overall survival 2) Sustained engraftment of genetically corrected haematopoietic stem cells in peripheral blood and/or in bone marrow 3) Expression of vector-derived WASP 4) Improved T-cell functions 5) Antigen-specific responses to vaccination 6) Improved platelet count;Timepoint(s) of evaluation of this end point: -Ematologic recovery: + 60 days-Safety to quickly treated cell infusion: absence of adverse reactions within 48 hours-long term Safety of infusion treated cells: RCL at baseline, after 1, 3, 6, 12 months and 24 months.;Main Objective: Primary objectives: 1) To evaluate the safety of the administration of autologous CD34+ cells transduced with a lentiviral vector containing the WASP gene in patients with WAS, after a reduced intensity conditioning regimen. 2) To evaluate the long-term engraftment of WASP-expressing transduced cells. 3) To evaluate the efficacy of gene therapy assessed as: 3.1 Improvement of the patient s immune function (specially T cell function and antigen-specific responses to vaccinations). 3.2 Improvement of thrombocytopenia.;Secondary Objective: To evaluate the efficacy of gene therapy in improving the patients s clinical condition, assessed by a reduction in frequency of severe infections, and bleeding episodes and reduction of auto-immunity phenomena and eczema.

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Secondary

Measure	Time frame
Secondary end point(s): Efficacy and safety-multilineage engraftment of cells genetically corrected – reduced frequency of serious infections reduced episodes of bruising and bleeding-reduction of Autoimmunity and eczema-improving the quality of life;Timepoint(s) of evaluation of this end point: -lack of immune response to transgene measured using WASP antibodies (immunoblot analysis): na presence of cells and expression of the gene proper WASp: screening, baseline, + 30 days, 60 days, 90 days, 180 days, 1 year, 2 years +1.5 years, +2.5 years, 3 years	—

Measure

Time frame

Secondary end point(s): Efficacy and safety-multilineage engraftment of cells genetically corrected – reduced frequency of serious infections reduced episodes of bruising and bleeding-reduction of Autoimmunity and eczema-improving the quality of life;Timepoint(s) of evaluation of this end point: -lack of immune response to transgene measured using WASP antibodies (immunoblot analysis): na presence of cells and expression of the gene proper WASp: screening, baseline, + 30 days, 60 days, 90 days, 180 days, 1 year, 2 years +1.5 years, +2.5 years, 3 years

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Countries

Italy

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026