Lentiviral Gene Therapy for X-Linked Chronic Granulomatous Disease (X-CGD)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Granulomatous Disease, Chronic, X-linked, Variant |
Genetic: pCCLchimGp91s lentiviral vector transduced CD34+ cells infusion |
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 Gene Therapy Protocol for X-Linked Chronic Granulomatous Disease |
- Overall survival following gene therapy [ Time Frame: 3 years follow up ] [ Designated as safety issue: No ]
- Reduction in frequency of infections [ Time Frame: evaluated from 1st year after treatment by clinical history, complete physical examination, haematological and microbiological tests ] [ Designated as safety issue: No ]
- Long term immune reconstitution [ Time Frame: 3 years follow up ] [ Designated as safety issue: No ]
| Enrollment: | 0 |
| Study Start Date: | November 2011 |
| Estimated Study Completion Date: | November 2016 |
| Estimated Primary Completion Date: | November 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: pCCLchimGp91s lentiviral vector transduced CD34+ cells
pCCLchimGp91s lentiviral vector transduced CD34+ cells will be infused in a volume of 50-100 mls intravenously over 30-45 minutes
|
Genetic: pCCLchimGp91s lentiviral vector transduced CD34+ cells infusion
pCCLchimGp91s lentiviral vector transduced CD34+ cells will be infused in a volume of 50-100 mls intravenously over 30-45 minutes
|
Eligibility| Ages Eligible for Study: | up to 30 Years |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United Kingdom | |
| Great Ormond Street Hospital for Children NHS Trust | |
| London, United Kingdom, WC1N 3JH | |
| Principal Investigator: | Adrian Thrasher, 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: | NCT01381003 History of Changes |
| Other Study ID Numbers: | 11-MI-03 |
| Study First Received: | June 23, 2011 |
| Last Updated: | June 1, 2012 |
| Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency United Kingdom: Research Ethics Committee |
Keywords provided by Great Ormond Street Hospital for Children NHS Foundation Trust:
|
Chronic Granulomatous Disease Gene therapy X-CGD NADPH-oxidase gp91-phox |
Additional relevant MeSH terms:
|
Genetic Diseases, X-Linked Genetic Diseases, Inborn Chronic Disease Granulomatous Disease, Chronic Granuloma Disease Attributes Pathologic Processes |
Phagocyte Bactericidal Dysfunction Leukocyte Disorders Hematologic Diseases Immunologic Deficiency Syndromes Immune System Diseases Lymphoproliferative Disorders Lymphatic Diseases |
ClinicalTrials.gov processed this record on May 19, 2013