Lentiviral Gene Therapy for Adenosine Deaminase (ADA) Deficiency

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2012 by Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor:
Information provided by:
Great Ormond Street Hospital for Children NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01380990
First received: June 23, 2011
Last updated: April 2, 2012
Last verified: April 2012
  Purpose

Adenosine Deaminase (ADA) is an enzyme, needed by body to develop lymphocytes of the immune system. Children who are born in mutations with mutations in ADA gene have severe combined immunodeficiency (SCID). Children with ADA-deficient SCID generally die in the first year of life from severe infections because they do not have immune system that can fight against infections. ADA deficient individuals can be cured by bone marrow transplant, but the best results are obtained when there is fully matched family donor is available. In the absence of a matched related donor, transplants from unrelated or mismatched donors have a much worse outcome. There is a form of enzyme therapy (PEG-ADA) for ADA-deficient SCID, in which children receive injections of purified ADA enzyme 1-2 times each week. These injections can allow the immune system to recover to a level that protects children from infections.

However, these injections have to be given weekly and are very expensive (£ 125,000 - 200,000 annually) and the recovery of the immune system is not sustained over time.

Gene therapy for ADA-deficient SCID could be performed by introducing a normal copy of the human ADA gene into the blood forming stem cells of the patient's bone marrow by using a new type of gene delivery system (in this trial called a lentiviral vector). The gene corrected cells are then transplanted back into the patient after small dose of chemotherapy. These gene corrected stem cells can survive into the body and make lymphocytes. In this trial, we will determine whether gene therapy for ADA-deficient SCID using lentiviral vector is safe, feasible and effective


Condition Intervention Phase
Adenosine Deaminase Deficiency
Severe Combined Immunodeficiencies (SCID)
Genetic: EF1αS-ADA lentiviral vector transduced patient Cd34+ cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II, Non-controlled, Open-label, Non-randomised, Single-centre Trial to Assess the Safety and Efficacy of EF1αS-ADA Lentiviral Vector Mediated Gene Modification of Autologous CD34+ Cells From ADA-deficient Individuals

Resource links provided by NLM:


Further study details as provided by Great Ormond Street Hospital for Children NHS Foundation Trust:

Primary Outcome Measures:
  • Overall survival following gene therapy [ Time Frame: 3 years follow up ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Reduction in frequency of infections [ Time Frame: evaluated from 1st year after treatment by clinical history, complete physical examinations, haematological and microbiological tests ] [ Designated as safety issue: Yes ]
  • Long term immune reconstitution as assessed by sustained improvement in thymic function [ Time Frame: 3 years follow up ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: November 2011
Estimated Study Completion Date: November 2021
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EF1αS-ADA lentiviral vector transduced patient Cd34+ cells Genetic: EF1αS-ADA lentiviral vector transduced patient Cd34+ cells
EF1αS-ADA lentiviral vector transduced patient Cd34+ cells will be infused in a volume of ~10-20 mls/kg intravenously over 30-45 minutes.

  Eligibility

Ages Eligible for Study:   up to 5 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of ADA-SCID confirmed by DNA sequencing or by confirmed absence of <3% of ADA enzymatic activity in peripheral blood (or for neonates) 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
  • Patients who lack a fully HLA-matched family donor
  • Patients < 5 years of age
  • Parental/guardian signed informed consent

Exclusion Criteria:

  • Patients who have a fully HLA-matched family donor
  • Patients > 5 years of age
  • Cytogenetic abnormalities on peripheral blood
  • Evidence of infection with HIV-1&2, hepatitis B, HCV
  • Evidence of active malignant disease
  • Known sensitivity to busulfan
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01380990

Contacts
Contact: Bobby Gaspar, Professor +44 (0)207 905 2319 H.Gaspar@ucl.ac.uk

Locations
United Kingdom
Great Ormond Street Hospital for Children NHS Trust Not yet recruiting
London, United Kingdom, WC1N 3JH
Contact: Bobby Gaspar, Professor    +44 (0)207 905 2319    H.Gaspar@ucl.ac.uk   
Principal Investigator: Bobby Gaspar, Professor         
Principal Investigator: Adrian Thrasher, Professor         
Sponsors and Collaborators
Great Ormond Street Hospital for Children NHS Foundation Trust
Investigators
Principal Investigator: Bobby Gaspar, Professor Great Ormond Street Hospital for Children NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Biren Patel, Great Ormond Street Hospital for Children NHS Trust
ClinicalTrials.gov Identifier: NCT01380990     History of Changes
Other Study ID Numbers: 10-MI-29
Study First Received: June 23, 2011
Last Updated: April 2, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Agammaglobulinemia
Immunologic Deficiency Syndromes
Severe Combined Immunodeficiency
Blood Protein Disorders
DNA Repair-Deficiency Disorders
Hematologic Diseases
Immune System Diseases
Infant, Newborn, Diseases
Lymphatic Diseases
Lymphoproliferative Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 22, 2014