Clinical trial NCT01855685: Gene Therapy for X-linked Chronic Granulomatous Disease (X-CGD)
Official title: A Phase I/II, Non Randomized, Multicenter, Open-label Study of Autologous CD34+ Cells Transduced With the G1XCGD Lentiviral Vector in Patients With X-linked Chronic Granulomatous Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: X-Linked Chronic Granulomatous Disease
Keywords: XCGD, lentivirus, cellular therapy
Lead sponsor: Genethon
Sponsor class: OTHER
First posted: 2013-05-16
Enrollment: 3
Sex: MALE
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: X-linked chronic granulomatous disease (X-CGD) is a rare genetic disorder, which affects boys. It is caused by an error in a gene that makes part of the immune system. The basic defect lies in specialised white blood cells called phagocytic cells (or phagocytes), which are responsible for protection against infection by destroying invading bacteria and fungi. They do this by pouring large amounts of substances similar to bleach onto these organisms. In CGD, there is a defect in the system that makes the bleach, called the NADPH-oxidase. In X-CGD (which accounts for two thirds of patients), the defect lies in a gene which makes up a critical part of the NADPH-oxidase (known as gp91-phox), and the cells cannot make bleach-like substances. Therefore they kill bacteria and fungi poorly, and the patients suffer from severe and recurrent infections. This also results in inflammation which can damage parts of the body such as the lung and gut.

In many cases, patients can be adequately protected from infection by constant intake of antibiotics. However, in others, severe life-threatening infections break through. In some cases, inflammation in the bowel or urinary systems results in blockages which cannot be treated with antibiotics, and which may require the use of other drugs such as steroids. Development of curative treatments for CGD is therefore of great importance.


Eligibility criteria: Inclusion Criteria:

* Male X-CGD patients
* Molecular diagnosis confirmed by DNA sequencing
* At least one prior ongoing or resistant severe infection and/or inflammatory complications requiring hospitalisation despite conventional therapy
* No HLA-matched donor available after 3 months search unless the risk of waiting for a potential match or for performing an allogeneic transplant is considered unacceptable by the investigator

Exclusion Criteria:

* Contraindication for leukapheresis
* Contraindication for administration of conditioning medication
* Administration of gammainterferon within 30 days before the infusion of transduced autologous CD34+ cells

Primary outcomes:
measure: Safety of the procedure as measured by the incidence of adverse events
timeFrame: 24 months
measure: Restoration and stability over time of the NADPH functioning granulocytes assessed by a DHR test
timeFrame: 12 months
Secondary outcomes:
measure: Normalisation of nutritional status, growth, development, severe infection and/or inflammatory complication which recommended patient's inclusion
timeFrame: 24 months
measure: Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time
timeFrame: 24 months
measure: Immunological reconstitution
timeFrame: 24 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: University College London Hospital (UCLH)
city: London
country: United Kingdom
facility: Great Ormond Street Hospital NHS Foundation Trust
Study officials:
affiliation: Great Ormond Street Hospital NHS Foundation Trust - London - UK
name: Adrian Thrasher, MD, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Children's Hospital Zürich - Switzerland
name: Janine Reichenbach, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Hematology/Oncology, University Hospital Frankfurt and Institute for Biomedical Research, Georg-Speyer-Haus, Frankfurt - Germany
name: Hubert Serve, MD, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Free Hospital / University College London Hospital (UCLH)
name: Emma Morris, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: