Clinical trial NCT01381003: 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
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Granulomatous Disease, Chronic, X-linked, Variant
Keywords: Chronic Granulomatous Disease
Gene therapy
X-CGD
NADPH-oxidase
gp91-phox
Lead sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor class: OTHER
First posted: 2011-06-27
Enrollment: 0
Sex: MALE
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall survival following gene therapy
timeFrame: 3 years follow up
Secondary outcomes:
measure: Reduction in frequency of infections
timeFrame: evaluated from 1st year after treatment by clinical history, complete physical examination, haematological and microbiological tests
measure: Long term immune reconstitution
timeFrame: 3 years follow up
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Trust
Study officials:
affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Adrian Thrasher, Professor
role: PRINCIPAL_INVESTIGATOR
References: