Gene Therapy for ADA-SCID - Full Text View

Purpose

This study investigated the safety and efficacy of different gene therapy approaches for Severe Combined Immunodeficiency (SCID) caused by the deficiency of adenosine deaminase (ADA) enzyme. This is a severe condition that can be cured by HLA-matched sibling donor bone marrow transplantation. Patients were enrolled if no HLA-identical sibling donor was available and the patient showed evidence of failure of enzyme replacement therapy or this treatment was not a long-term available option. The aim of the study was to evaluate the safety and efficacy of the procedure and to identify the relative role of peripheral blood lymphocytes and hematopoietic stem cells and progenitor cells in the long-term reconstitution of immune functions after retroviral vector mediated ADA gene transfer.

Condition	Intervention	Phase
Severe Combined Immunodeficiency Syndrome	Genetic: gene transduced PBL and/or gene transduced HSC	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Treatment of ADA-SCID by Gene Therapy on Somatic Cells

Resource links provided by NLM:

Genetics Home Reference related topics: adenosine deaminase deficiency complement factor I deficiency purine nucleoside phosphorylase deficiency X-linked severe combined immunodeficiency ZAP70-related severe combined immunodeficiency

U.S. FDA Resources

Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:

Evaluation of safety of the administration of the autologous PBL and/or autologous HSC transduced with the normal human ADA gene [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Evaluation of extent, kinetic and duration of the engraftment of transduced cells and the potential selective advantage of ADA positive cells [ Designated as safety issue: No ]
Evaluation of efficacy of the administration of autologous PBL/HSC(Clinical, immunological, hematological, microbiological, ADA activity and purine metabolism) [ Designated as safety issue: No ]
To identify the relative role of peripheral blood lymphocytes and hematopoietic stem cells and progenitor cells in the long-term reconstitution of immune functions after gene therapy

Enrollment:	8
Study Start Date:	March 1992
Study Completion Date:	January 2007
Primary Completion Date:	July 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: PBL/HSC	Genetic: gene transduced PBL and/or gene transduced HSC infusions of autologous PBL and/or HSC transduced with retroviral vectors encoding ADA Other Name: gene therapy

Detailed Description:

This is mono-centric, non-randomized, non-controlled, open label, phase I-II trial that evaluated the safety and efficacy of ADA gene transfer into somatic cells for the treatment of ADA-SCID

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Lack of HLA-identical sibling donor and
Evidence of failure of the enzyme replacement treatment after >6 months or
PEG-ADA is not available as a life long option

Exclusion Criteria:

HLA identical bone marrow sibling donor
HIV infection
Malignancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00599781

Sponsors and Collaborators

IRCCS San Raffaele

Fondazione Telethon

Investigators

Principal Investigator:

Bordignon Claudio, MD

IRCCS San Raffaele

More Information

No publications provided by IRCCS San Raffaele

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sauer AV, Brigida I, Carriglio N, Hernandez RJ, Scaramuzza S, Clavenna D, Sanvito F, Poliani PL, Gagliani N, Carlucci F, Tabucchi A, Roncarolo MG, Traggiai E, Villa A, Aiuti A. Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID. Blood. 2012 Feb 9;119(6):1428-39. Epub 2011 Dec 19.

Cassani B, Montini E, Maruggi G, Ambrosi A, Mirolo M, Selleri S, Biral E, Frugnoli I, Hernandez-Trujillo V, Di Serio C, Roncarolo MG, Naldini L, Mavilio F, Aiuti A. Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapy. Blood. 2009 Oct 22;114(17):3546-56. Epub 2009 Aug 3.

Sauer AV, Mrak E, Hernandez RJ, Zacchi E, Cavani F, Casiraghi M, Grunebaum E, Roifman CM, Cervi MC, Ambrosi A, Carlucci F, Roncarolo MG, Villa A, Rubinacci A, Aiuti A. ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency. Blood. 2009 Oct 8;114(15):3216-26. Epub 2009 Jul 24.

Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, Callegaro L, Scaramuzza S, Andolfi G, Mirolo M, Brigida I, Tabucchi A, Carlucci F, Eibl M, Aker M, Slavin S, Al-Mousa H, Al Ghonaium A, Ferster A, Duppenthaler A, Notarangelo L, Wintergerst U, Buckley RH, Bregni M, Marktel S, Valsecchi MG, Rossi P, Ciceri F, Miniero R, Bordignon C, Roncarolo MG. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. 2009 Jan 29;360(5):447-58.

Responsible Party:	Claudio Bordignon, IRCCS San Raffaele
ClinicalTrials.gov Identifier:	NCT00599781 History of Changes
Other Study ID Numbers:	150291
Study First Received:	January 8, 2008
Last Updated:	January 23, 2008
Health Authority:	Italy: National Bioethics Committee

Keywords provided by IRCCS San Raffaele:

adenosine deaminase
SCID
gene therapy
retroviral vector

Additional relevant MeSH terms:

Immunologic Deficiency Syndromes
Severe Combined Immunodeficiency
Immune System Diseases

Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on May 21, 2013