X-Linked Chronic Granulomatous Disease
Conditions
Keywords
XCGD, lentivirus, cellular therapy
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.
Interventions
GENETICX vivo gene therapy
Transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing GP91PHOX gene
Sponsors
Genethon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
6 Months to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety of the procedure as measured by the incidence of adverse events | 24 months |
| Restoration and stability over time of the NADPH functioning granulocytes assessed by a DHR test | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Normalisation of nutritional status, growth, development, severe infection and/or inflammatory complication which recommended patient's inclusion | 24 months |
| Percentage of transduced CD34+ haematopoietic cells infused and of blood cells over time | 24 months |
| Immunological reconstitution | 24 months |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORAdrian Thrasher, MD, PHD
Great Ormond Street Hospital NHS Foundation Trust - London - UK
PRINCIPAL_INVESTIGATORJanine Reichenbach, MD
University Children's Hospital Zürich - Switzerland
PRINCIPAL_INVESTIGATORHubert Serve, MD, PHD
Department of Hematology/Oncology, University Hospital Frankfurt and Institute for Biomedical Research, Georg-Speyer-Haus, Frankfurt - Germany
PRINCIPAL_INVESTIGATOREmma Morris, MD, PHD
Royal Free Hospital / University College London Hospital (UCLH)
Outcome results
None listed