Lentiviral Gene Therapy for X-Linked Chronic Granulomatous Disease (X-CGD)
Primary Purpose
Granulomatous Disease, Chronic, X-linked, Variant
Status
Withdrawn
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
pCCLchimGp91s lentiviral vector transduced CD34+ cells infusion
Sponsored by
About this trial
This is an interventional treatment trial for Granulomatous Disease, Chronic, X-linked, Variant focused on measuring Chronic Granulomatous Disease, Gene therapy, X-CGD, NADPH-oxidase, gp91-phox
Eligibility Criteria
Inclusion Criteria:
- History of at least one severe infection requiring hospitalisation despite standard antimicrobial prophylaxis and/or inflammation complications including one of the following: Oesophageal obstruction, gastric outlet obstruction, bladder outlet obstruction or colitis
- Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or significantly reduced biochemical activities of the NADPH-oxidase
- Parental/Guardian and where appropriate Child's signed consent/assent
Exclusion Criteria:
- 10/10 HLA identical (A,B,C,DR,DQ) family or unrelated or cord blood donor unless there is deemed to be an unacceptable risk associated with an allogeneic procedure
- Contraindication for leukapheresis (anaemia Hb <8g/dl, cardiovascular instability, severe coagulopathy) or for administration of conditioning medication
Sites / Locations
- Great Ormond Street Hospital for Children NHS Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
pCCLchimGp91s lentiviral vector transduced CD34+ cells
Arm Description
pCCLchimGp91s lentiviral vector transduced CD34+ cells will be infused in a volume of 50-100 mls intravenously over 30-45 minutes
Outcomes
Primary Outcome Measures
Overall survival following gene therapy
Secondary Outcome Measures
Reduction in frequency of infections
Long term immune reconstitution
Full Information
NCT ID
NCT01381003
First Posted
June 23, 2011
Last Updated
June 1, 2012
Sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT01381003
Brief Title
Lentiviral Gene Therapy for X-Linked Chronic Granulomatous Disease (X-CGD)
Official Title
Phase I/II Gene Therapy Protocol for X-Linked Chronic Granulomatous Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2012
Overall Recruitment Status
Withdrawn
Why Stopped
Study is withdrawn before recruting participants, new trial will be multi centre, sponsored by different organisation.
Study Start Date
November 2011 (undefined)
Primary Completion Date
November 2016 (Anticipated)
Study Completion Date
November 2016 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Chronic Granulomatous Disease (CGD) is a rare inherited disorder in which patients suffer from severe infection and inflammation. The first indication of disease usually appears in early childhood. The basic defect found to be lie in specialised white blood cells called phagocytic cells, which are responsible for engulfing and destroying germs. In CGD, there is a defect in an enzyme (known as NADPH-oxidase) that is responsible for generating bleach like substances that are important for killing some important germs. In the form of the disease known as X-CGD (which accounts for two thirds of patients), there are defined mistakes in a gene called gp91-phox, which is a key part of the NADPH-oxidase.
In many cases, patients can be protected from infection by constant intake of antibiotics. However, in others potential life-threatening infections break through. In some cases patients also develop serious inflammation requiring high doses of drugs such as steroids. CGD can be cured by bone marrow transplant, but the best results are available when there is matched donor available. Transplant from unmatched donor have a much worse outcome.
Gene therapy of CGD can be performed by introducing a normal copy of human gp91-phox gene into the blood forming stem cells of patients' bone marrow by using a gene carrier (in this study called lentiviral vector). After treatment of the bone marrow cells in a specialised laboratory are given back to the patient and will grow into functional phagocytic cells.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Granulomatous Disease, Chronic, X-linked, Variant
Keywords
Chronic Granulomatous Disease, Gene therapy, X-CGD, NADPH-oxidase, gp91-phox
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
pCCLchimGp91s lentiviral vector transduced CD34+ cells
Arm Type
Experimental
Arm Description
pCCLchimGp91s lentiviral vector transduced CD34+ cells will be infused in a volume of 50-100 mls intravenously over 30-45 minutes
Intervention Type
Genetic
Intervention Name(s)
pCCLchimGp91s lentiviral vector transduced CD34+ cells infusion
Intervention Description
pCCLchimGp91s lentiviral vector transduced CD34+ cells will be infused in a volume of 50-100 mls intravenously over 30-45 minutes
Primary Outcome Measure Information:
Title
Overall survival following gene therapy
Time Frame
3 years follow up
Secondary Outcome Measure Information:
Title
Reduction in frequency of infections
Time Frame
evaluated from 1st year after treatment by clinical history, complete physical examination, haematological and microbiological tests
Title
Long term immune reconstitution
Time Frame
3 years follow up
10. Eligibility
Sex
Male
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
History of at least one severe infection requiring hospitalisation despite standard antimicrobial prophylaxis and/or inflammation complications including one of the following: Oesophageal obstruction, gastric outlet obstruction, bladder outlet obstruction or colitis
Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or significantly reduced biochemical activities of the NADPH-oxidase
Parental/Guardian and where appropriate Child's signed consent/assent
Exclusion Criteria:
10/10 HLA identical (A,B,C,DR,DQ) family or unrelated or cord blood donor unless there is deemed to be an unacceptable risk associated with an allogeneic procedure
Contraindication for leukapheresis (anaemia Hb <8g/dl, cardiovascular instability, severe coagulopathy) or for administration of conditioning medication
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian Thrasher, Professor
Organizational Affiliation
Great Ormond Street Hospital for Children NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Great Ormond Street Hospital for Children NHS Trust
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Lentiviral Gene Therapy for X-Linked Chronic Granulomatous Disease (X-CGD)
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