Gene Therapy for ADA-SCID

NCT00599781 | Completed Phase 1

• 1 other identifier: 150291
• Study Type: interventional
• Target: 8
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Severe Combined Immunodeficiency Syndrome

Keywords

adenosine deaminase; SCID; gene therapy; retroviral vector

Outcome Measures

Primary Outcomes (1)

• Evaluation of safety of the administration of the autologous PBL and/or autologous HSC transduced with the normal human ADA gene

Secondary Outcomes (3)

• Evaluation of extent, kinetic and duration of the engraftment of transduced cells and the potential selective advantage of ADA positive cells

• Evaluation of efficacy of the administration of autologous PBL/HSC(Clinical, immunological, hematological, microbiological, ADA activity and purine metabolism)

• 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

Study Arms (1)

PBL/HSC

EXPERIMENTAL

Genetic: gene transduced PBL and/or gene transduced HSC

Interventions

gene transduced PBL and/or gene transduced HSC GENETIC

infusions of autologous PBL and/or HSC transduced with retroviral vectors encoding ADA

Also known as: gene therapy

PBL/HSC

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• HLA identical bone marrow sibling donor
• HIV infection
• Malignancy

Sponsors & Collaborators

• IRCCS San Raffaele: lead
• Fondazione Telethon: collaborator

Related Publications (5)

• 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. doi: 10.1182/blood-2011-07-366781. Epub 2011 Dec 19.

  PMID: 22184407 DERIVED

• 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. doi: 10.1182/blood-2009-02-202085. Epub 2009 Aug 3.

  PMID: 19652199 DERIVED

• 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. doi: 10.1182/blood-2009-03-209221. Epub 2009 Jul 24.

  PMID: 19633200 DERIVED

• 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. doi: 10.1056/NEJMoa0805817.

  PMID: 19179314 DERIVED

• Cassani B, Mirolo M, Cattaneo F, Benninghoff U, Hershfield M, Carlucci F, Tabucchi A, Bordignon C, Roncarolo MG, Aiuti A. Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients. Blood. 2008 Apr 15;111(8):4209-19. doi: 10.1182/blood-2007-05-092429. Epub 2008 Jan 24.

  PMID: 18218852 DERIVED

MeSH Terms

Conditions

Severe Combined Immunodeficiency

Interventions

Genetic Therapy

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Genetic Engineering; Genetic Techniques; Investigative Techniques

Study Officials

• Bordignon Claudio, MD

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 8, 2008
• First Posted: January 24, 2008
• Study Start: March 1, 1992
• Primary Completion: July 1, 2006
• Study Completion: January 1, 2007
• Last Updated: January 24, 2008

Record last verified: 2007-12