Gene Therapy ADA Deficiency

Condition(s) targeted: Adenosine Deaminase Deficiency

Intervention: Intravenous infusion of transduced cells (Biological)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Great Ormond Street Hospital for Children NHS Foundation Trust

Overall contact:
Bobby Gaspar, Professor, Phone: 020 7905 2319, Email: H.Gaspar@ich.ucl.ac.uk

Adenosine deaminase deficiency is an inherited disorder that results in severe abnormalities of the immune system and leaves children unable to fight infection. This trial aims to treat adenosine deaminase deficiency patients using gene therapy.

Official title: Phase I Gene Therapy Protocol for Adenosine Deaminase Deficiency

Study design: Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Immunological reconstitution

Secondary outcome:

Incidence of adverse reactions

Molecular characterisation of gene transfer

Normalisation of nutritional status, growth, and development

Minimum age: N/A. Maximum age: 18 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Patients who lack a human leukocyte antigen (HLA)-genotypically identical bone marrow donor OR phenotypically matched family or unrelated donor AND who show incomplete immune reconstitution on Polyethylene glycol-modified adenosine deaminase (PEG-ADA) enzyme replacement therapy (defined by absolute CD4+ count <300 cell/mm3 and who remain on immunoglobulin replacement therapy)

2. Diagnosis of ADA-SCID (Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA)confirmed by DNA sequencing OR by confirmed absence of <3% of ADA enzymatic activity in peripheral blood or (for neonates) in umbilical cord blood erythrocytes and/or leukocytes or in cultured fetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of PEG-ADA replacement therapy

3. Parental/guardian/patient signed informed consent

Bobby Gaspar, Professor, Phone: 020 7905 2319, Email: H.Gaspar@ich.ucl.ac.uk

Great Ormond Street Hospital for Children NHS Trust, London WC1N 1EH, United Kingdom; Recruiting
Bobby Gapar, Professor, Phone: 020 7905 2319, Email: H.Gaspar@ich.ucl.ac.uk
Bobby Gaspar, Professor, Principal Investigator

Related publications:

Aiuti A, Slavin S, Aker M, Ficara F, Deola S, Mortellaro A, Morecki S, Andolfi G, Tabucchi A, Carlucci F, Marinello E, Cattaneo F, Vai S, Servida P, Miniero R, Roncarolo MG, Bordignon C. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science. 2002 Jun 28;296(5577):2410-3.

Hoogerbrugge PM, van Beusechem VW, Fischer A, Debree M, le Deist F, Perignon JL, Morgan G, Gaspar B, Fairbanks LD, Skeoch CH, Moseley A, Harvey M, Levinsky RJ, Valerio D. Bone marrow gene transfer in three patients with adenosine deaminase deficiency. Gene Ther. 1996 Feb;3(2):179-83.

Hershfield MS. PEG-ADA: an alternative to haploidentical bone marrow transplantation and an adjunct to gene therapy for adenosine deaminase deficiency. Hum Mutat. 1995;5(2):107-12. Review.

Starting date: October 2003
Last updated: March 1, 2012