HAEMATOPOIETIC STEM CELL GENE THERAPY

• Register: EUCTR
• Last refreshed on: 12 March 2024
• Main ID: EUCTR2009-017346-32-IT
• Date of registration: 26/04/2010
• Prospective Registration: No
• Primary sponsor: Fondazione Telethon
• Public title: HAEMATOPOIETIC STEM CELL GENE THERAPY
• Scientific title: A PHASE I/II CLINICAL TRIAL OF HAEMATOPOIETIC STEM CELL GENE THERAPY FOR THE WISKOTT-ALDRICH SYNDROME - TIGET-WAS
• Date of first enrolment: 15/03/2010
• Target sample size: 8
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-017346-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy

Contacts

• Affiliation: Fondazione Telethon

• Affiliation: Fondazione Telethon

Key inclusion & exclusion 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:
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


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

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

Intervention(s)

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 infusion
INN or Proposed INN: FLUDARABINA
CAS Number: 75607-67-9
Current Sponsor code: na
Other descriptive name: FLUDARABINA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: MOZOBIL - 20 MG/ML - SOLUZIONE INIETTABILE - USO SOTTOCUTANEO - FLACONCINO (VETRO) - 24 MG/1.2 ML 1 FLACONCINO
Product Name: PLERIXAFOR
Product Code: [na]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PLERIXAFOR
CAS Number: 0110078-46-1
Current Sponsor code: na
Other descriptive name: Plerixafor
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: MYELOSTIM - 34 1 FLACONCINO LIOFILIZZATO 33.6 MIU + SIRINGA PRERIEMPITA SOLVENTE 1 ML
Product Name: na
Product Code: [na]
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: LENOGRASTIM
CAS Number: 135968-09-1
Current Sponsor code: na
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 34-

Trade Name: MABTHERA - 2 FIALE 100 MG 10 ML
Product Name: RITUXIMAB
Product Code: [na]
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Sponsor code: na
Other descriptive name: RITUXIMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: BUSILVEX - 6 MG/ML - CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO - 10 ML 8 FLACONCINI
Product Name: na
Product Code: [na]
Pharmaceutical Form: Solution for infusion

Primary Outcome(s)

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.

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.

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.

Secondary Outcome(s)

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

Secondary ID(s)

201228

Ethics review

Status: Approved
Approval date: 03/12/2009
Contact: