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ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID (Gene-ADA)
This study is currently recruiting participants.
Verified by IRCCS San Raffaele, January 2008
Sponsors and Collaborators: IRCCS San Raffaele
Fondazione Telethon
Information provided by: IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT00598481
  Purpose

This is a phase I/II protocol to evaluate the safety and efficacy of ADA gene transfer into hematopoietic stem/progenitor cells for the treatment of adenosine deaminase (ADA)-deficiency. This condition is an autosomal recessive form of Severe Combined Immunodeficiency (SCID) characterized by impaired immune responses, recurrent infections, failure to thrive and systemic toxicity due to accumulation of purine metabolites. Transplants from an HLA-identical sibling donor is the treatment of choice, but available for a minority of patients. The use of alternative bone marrow donors or enzyme replacement therapy is associated with important drawbacks. The drug product studied in this protocol consists of autologous CD34+ hematopoietic stem/progenitor cells engineered ex vivo with a retroviral vector encoding the therapeutic gene ADA. The engineered CD34+ cells are infused following a nonmyeloablative conditioning with busulfan to make space in the bone marrow. The study objectives are: a) to evaluate the safety and the clinical efficacy of gene therapy, in the absence of enzyme replacement therapy; b) to evaluate the biological activity (engraftment, ADA expression) of ADA transduced CD34+ cells and their hematopoietic progeny. c) to evaluate the immunological reconstitution and purine metabolism after gene therapy.


Condition Intervention Phase
Severe Combined Immunodeficiency
Genetic: Gene transduced CD34+ cells
Phase I
Phase II

Genetics Home Reference related topics: adenosine deaminase deficiency X-linked severe combined immunodeficiency
Drug Information available for: Busulfan Adenosine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: ADA Gene Transfer Into Hematopoietic Stem/Progenitor Cells for the Treatment of ADA-SCID

Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • survival [ Time Frame: minimum of 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in the rate of severe infection [ Time Frame: During follow up ] [ Designated as safety issue: No ]
  • T-lymphocyte counts [ Time Frame: one year ] [ Designated as safety issue: No ]
  • Modification of the systemic metabolic defect [ Time Frame: one year ] [ Designated as safety issue: No ]
  • presence of genetically modified cells in the BM and PB [ Time Frame: one year ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: October 2002
Arms Assigned Interventions
CD34+ cells: Experimental Genetic: Gene transduced CD34+ cells
infusion of autologous CD34+ cells transduced with retroviral vector encoding ADA after non-myeloablative conditioning with Busulphan

Detailed Description:

The safety of the study will be evaluated by description of all adverse events and adverse drug reactions.

The study is aimed at reaching the minimum sample size of ten patients.

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ADA-SCID with no HLA-identical sibling donor
  • Pediatric age and at least one of the following criteria:
  • inadequate immune response after PEG-ADA for > 6 months
  • patients who discontinued PEG-ADA due to intolerance, allergy or auto-immunity
  • patients for whom enzyme replacement therapy is not a life long therapeutic option

Exclusion Criteria:

  • HIV infection
  • History or current malignancy
  • previous gene therapy in 12 months preceding the enrollment
  • any other conditions dangerous for the patients according to the investigator
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00598481

Contacts
Contact: Luciano Callegaro callegaro.luciano@hsr.it
Contact: Valentina Bergamante bergamante.valentina@hsr.it

Locations
Italy, MI
Pediatric Clinical Research Unit, HSR-TIGET Recruiting
Milano, MI, Italy, 20132
Contact: Maria Grazia Roncarolo, MD     +390226434875     roncarolo.mariagrazia@hsr.it    
Contact: Alessandro Aiuti, MD, PhD     +390226434435     a.aiuti@hsr.it    
Principal Investigator: Maria Grazia Roncarolo, MD            
Principal Investigator: Alessandro Aiuti, MD, PhD            
Sponsors and Collaborators
IRCCS San Raffaele
Fondazione Telethon
Investigators
Principal Investigator: Maria Grazia Roncarolo, Director IRCCS San Raffaele - Telethon Institute for Gene Therapy
Principal Investigator: Alessandro Aiuti IRCCS San Raffaele - Telethon Institute for Gene Therapy
  More Information

Publications indexed to this study:
Responsible Party: HSR-TIGET, IRCCS San Raffaele ( Maria Grazia Roncarolo )
Study ID Numbers: 15386-PRE21
Study First Received: January 10, 2008
Last Updated: January 21, 2008
ClinicalTrials.gov Identifier: NCT00598481  
Health Authority: Italy: National Institute of Health

Keywords provided by IRCCS San Raffaele:
Adenosine deaminase
retroviral vector
gene therapy
SCID

Study placed in the following topic categories:
Metabolic Diseases
Severe Combined Immunodeficiency
Busulfan
Infant, Newborn, Diseases
Severe combined immunodeficiency
Metabolic disorder
Adenosine
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Immune System Diseases
DNA Repair-Deficiency Disorders

ClinicalTrials.gov processed this record on January 14, 2009