Granulomatous Disease, Chronic, X-linked, Variant Clinical Trial
Official title:
Phase I/II Gene Therapy Protocol for X-Linked Chronic Granulomatous Disease
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.
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | November 2016 |
| Est. primary completion date | November 2016 |
| Accepts healthy volunteers | No |
| Gender | Male |
| Age group | N/A to 30 Years |
| Eligibility |
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 |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | Great Ormond Street Hospital for Children NHS Trust | London |
| Lead Sponsor | Collaborator |
|---|---|
| Great Ormond Street Hospital for Children NHS Foundation Trust |
United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall survival following gene therapy | 3 years follow up | No | |
| Secondary | Reduction in frequency of infections | evaluated from 1st year after treatment by clinical history, complete physical examination, haematological and microbiological tests | No | |
| Secondary | Long term immune reconstitution | 3 years follow up | No |