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Lentiviral Gene Therapy for Adenosine Deaminase (ADA) Deficiency

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01380990
Recruitment Status : Active, not recruiting
First Posted : June 27, 2011
Last Update Posted : August 10, 2018
Information provided by (Responsible Party):
Great Ormond Street Hospital for Children NHS Foundation Trust

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : November 2012
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Overall survival following gene therapy [ Time Frame: 3 years follow up ]

Secondary Outcome Measures :
  1. Reduction in frequency of infections [ Time Frame: evaluated from 1st year after treatment by clinical history, complete physical examinations, haematological and microbiological tests ]
  2. Long term immune reconstitution as assessed by sustained improvement in thymic function [ Time Frame: 3 years follow up ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 5 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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
  2. Patients who lack a fully Human leukocyte antigen (HLA)-matched family donor
  3. Patients (male or female) <5 years of age OR Patients (male or female) ≥ 5 years to 15 years of age who have preserved thymic function as evidenced by presence of >10 % naïve T cells (CD4+45RA+27+ cells)
  4. Parental/guardian signed informed consent

Exclusion Criteria:

  1. Cytogenetic abnormalities on peripheral blood
  2. Evidence of active malignant disease
  3. Known sensitivity to busulfan
  4. If applicable, confirmed pregnancy (to be tested in patients above 12 years old)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01380990

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United Kingdom
Great Ormond Street Hospital for Children NHS Trust
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
Great Ormond Street Hospital for Children NHS Foundation Trust
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Principal Investigator: Claire Booth, Dr Great Ormond Street Hospital NHS Foundation Trust

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Responsible Party: Great Ormond Street Hospital for Children NHS Foundation Trust Identifier: NCT01380990    
Other Study ID Numbers: 10-MI-29
First Posted: June 27, 2011    Key Record Dates
Last Update Posted: August 10, 2018
Last Verified: August 2018
Additional relevant MeSH terms:
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Severe Combined Immunodeficiency
Immunologic Deficiency Syndromes
Immune System Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases