Gene Therapy for X-CGD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01906541
Recruitment Status : Recruiting
First Posted : July 24, 2013
Last Update Posted : August 2, 2013
Information provided by (Responsible Party):
Hubert Serve, Prof., MD, Johann Wolfgang Goethe University Hospitals

July 15, 2013
July 24, 2013
August 2, 2013
July 2013
December 2013   (Final data collection date for primary outcome measure)
  • Transduction rate of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral CD34+ cells from CGD patients with a SIN gamma retroviral vector [ Time Frame: 1 week ]
  • Engraftment rate of the transduced CD34+ cells in the patients [ Time Frame: 5 years ]
  • Long-term expression of the transgene (rate of gp91phox positive cells) in circulating cells in the peripheral blood [ Time Frame: 5 years ]
  • Functional reconstitution of the NADPH oxidase in circulating cells of the peripheral blood (% DHR positive cells) [ Time Frame: 5 years ]
  • Frequency and severity of unexpected toxic adverse events during and after infusion of the genetically modified CD34+ cells [ Time Frame: 5 years ]
Same as current
Complete list of historical versions of study NCT01906541 on Archive Site
  • Frequency of infections as indicator for the clinical benefit for the patients [ Time Frame: 5 years ]
  • Proliferation rate of CD34+ cells in ex-vivo culture under serum-free conditions [ Time Frame: up to 3 weeks ]
  • Differentiation rate of CD34+ cells (as measured by flow cytometry) in ex-vivo culture under serum-free conditions [ Time Frame: up to 3 weeks ]
  • Transduction rate of CD34+ cells in ex-vivo culture under serum-free conditions [ Time Frame: up to 12 weeks ]
Same as current
Not Provided
Not Provided
Gene Therapy for X-CGD
A Phase I/II Gene Therapy Trial for X-CGD With a SIN Gammaretroviral Vector

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 gp91phox subunit of the NADPH oxidase complex. X-CGD patients suffer from recurrent and life-threatening infections and severe hyperinflammatory complications.

The only curative treatment for X-CGD is allogenic hematopoietic stem cell transplantation, but this procedure implies severe risks and many patients lack an appropriate donor. Therefore alternative curative approaches are urgently needed. In this study, patients will be treated with gene-corrected autologous CD34+ cells, using a SIN gammaretroviral vector for ex-vivo gene-therapy.

Not Provided
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
X-linked Chronic Granulomatous Disease
Genetic: ex-vivo gene-therapy
transplantation autologous CD34+ cells, transduced with a SIN gammaretroviral vector
Experimental: ex-vivo gene-therapy
transplantation of genetically modified autologous CD34+ cells
Intervention: Genetic: ex-vivo gene-therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
December 2019
December 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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 Criteria:

  • 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)
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact: Hubert Serve, Prof., MD 0049/69/6301 ext 4634
Contact: Joachim Schwäble, MD 0049/69/67824900
Not Provided
Not Provided
Hubert Serve, Prof., MD, Johann Wolfgang Goethe University Hospitals
Hubert Serve, Prof., MD
Not Provided
Not Provided
Johann Wolfgang Goethe University Hospital
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP