Status:
UNKNOWN
Gene Therapy for X-CGD
Lead Sponsor:
Hubert Serve, Prof., MD
Conditions:
X-linked Chronic Granulomatous Disease
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
X-linked chronic granulomatous disease (X-CGD) is a rare inherited immune defect, which is caused by the inability of phagocytic cells to produce reactive oxygen species due to a defect in the gp91pho...
Eligibility Criteria
Inclusion
- Verified diagnosis of the X-linked form of chronic granulomatous disease, with loss of gp91phox expression (Western Blot). Evidence of less than 5% of normal oxidase production in circulating neutrophil granulocytes as measured by dihydrorhodamine- (DHR-) and nitro blue tetrazolium- (NBT-) assay
- History of severe chronic infections with life-threatening course or severe steroid- sensitive or steroid insensitive granulomatous disease, with necessity of inpatient treatment, without sustained improvement even under maximum conservative treatment measures
- No Human Leukocyte Antigen (HLA) identical (10/10 match) sibling- or unrelated donor, or contraindications for allogenic stem cell transplantation in presence of a suitable donor. The lack of an HLA-identical (10/10 match) sibling- or unrelated donor has to be confirmed by an unsuccessful search in national and international donor registers for at leat 3 months
- Normal organ-function: glomerular filtration rate (GFR) ≥ 60ml/min., Bilirubin ≤ 1.5-fold upper reference-level, normal parameters for liver enzymes and clotting (TPZ 75-100%, partial thromboplastin time (PTT) 30-38sec, Fibrinogen 200-400mg/dl), Leukocytes \> 3 x 10\^9/l, Granulocytes \> 1.5 x 10\^9/l, Thrombocytes \>100 x 10\^9/l
- Contraception from start of G-CSF application until 1 year after retransfusion of the gene-corrected cells
- No interferon-gamma injection within two weeks prior to hematopoietic stem cell mobilization
- Karnofsky-Index \> 70%
- Signed informed consent
Exclusion
- Patients with non-controlled acute infections
- Severe cardiac or pulmonary malfunctions: ejection fraction \< 60%, valvular heart disease \> II°, arrhythmia requiring therapy, forced expiratory volume at one second/vital capacity (FEV1/VC) \< 75% , diffusion capacity of lung for carbon monoxide (DLCO) \<60%
- Bilirubin \> 1.5-fold upper reference-level
- HIV-, Hepatitis B- or C - infection
- Contraindications for G-CSF administration, as autoimmune vasculitis.
- Contraindications for stem cell apheresis, as low hemoglobin \< 8g/dl, cardiovascular instability or severe coagulopathy
- Pregnancy or breast-feeding
- Drug- or alcohol-abuse
- Lack of search for an unrelated donor
- Patients with a HLA 9/10 mismatched unrelated donor (MMUD) will be excluded, if a thorough risk-benefit analysis favors allogenic hematopoietic stem cell transplantation (HSCT)
Key Trial Info
Start Date :
July 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2019
Estimated Enrollment :
5 Patients enrolled
Trial Details
Trial ID
NCT01906541
Start Date
July 1 2013
End Date
December 1 2019
Last Update
August 2 2013
Active Locations (1)
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1
University Hospital Frankfurt
Frankfurt am Main, Germany, 60595