Gene Therapy for X-linked Chronic Granulomatous Disease
Stopped: Las patient early withdrawed from the study
France3 participantsStarted 2013-06-24
Plain-language summary
X-linked chronic granulomatous disease (X-CGD) is a rare genetic disorder, which affects boys. It is a primary immunodeficiency disorder which results from an inability of the white blood cells called phagocytic cells (or phagocytes) to kill invading bacteria and fungi. These cells have difficulty forming the free radicals (most importantly the superoxide radical due to defective phagocyte NADPH oxidase complex) which are important in the killing of ingested pathogens. In X-CGD (which accounts for two thirds of CGD patients), the defect lies in a gene which makes up a critical part of the NADPH-oxidase complex (the catalytic subunit; gp91-phox protein). 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.
Who can participate
Age range
24 Months
Sex
MALE
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* Male X-CGD patients \>23 months of age. Youngest patients (\>1 month and ≤ 23 months) may be enrolled at physician's appreciation; in this case mobilization of peripheral HSC may be replaced by two bone marrow harvests.
* Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or reduction \> 70% of the biochemical activity of the NAHPD-oxidase.
* At least one ongoing or resistant or at high risk of relapse 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.
* No co-infection with Human Immunodeficiency Virus (HIV) or hepatitis B virus (HBs Ag positive) or hepatitis C virus (anti-HCV Ab positive).
* Written informed consent for adult patient.
* Parental/guardian and where appropriate child's signed consent/assent.
Exclusion Criteria:
* 10/10 HLA identical (A, B, C, DR, DQ) family or unrelated.
* Contraindication for leukapheresis (anaemia Hb \<8g/dl, cardiovascular instability, severe coagulopathy).
* Contraindication for administration of conditioning medication and any component of the Investigational Medicinal Product (IMP) preparation.
* Administration of gamma interferon within 30 days before the infusion of transduced autologous CD34+ cells.
* Participation in another experimenta…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Safety as measured by the incidence of adverse events
Timeframe: 60 months
2
Restoration and stability over time of the NADPH functioning granulocytes assessed by a Dihydrorhodamine (DHR) flow cytometry test