Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Gene Therapy for X-CGD

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Johann Wolfgang Goethe University Hospital
Information provided by (Responsible Party):
Hubert Serve, Prof., MD, Johann Wolfgang Goethe University Hospitals Identifier:
First received: July 15, 2013
Last updated: August 1, 2013
Last verified: August 2013

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.

Condition Intervention Phase
X-linked Chronic Granulomatous Disease
Genetic: ex-vivo gene-therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Gene Therapy Trial for X-CGD With a SIN Gammaretroviral Vector

Resource links provided by NLM:

Further study details as provided by Johann Wolfgang Goethe University Hospital:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 5
Study Start Date: July 2013
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ex-vivo gene-therapy
transplantation of genetically modified autologous CD34+ cells
Genetic: ex-vivo gene-therapy
transplantation autologous CD34+ cells, transduced with a SIN gammaretroviral vector


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01906541

Contact: Hubert Serve, Prof., MD 0049/69/6301 ext 4634
Contact: Joachim Schwäble, MD 0049/69/67824900

University Hospital Frankfurt Recruiting
Frankfurt am Main, Germany, 60595
Contact: Joachim Schwäble, MD    0049/69 /67824900   
Sponsors and Collaborators
Hubert Serve, Prof., MD
  More Information

Responsible Party: Hubert Serve, Prof., MD, Head of Medical Department II, Johann Wolfgang Goethe University Hospitals Identifier: NCT01906541     History of Changes
Other Study ID Numbers: X-CGD
Study First Received: July 15, 2013
Last Updated: August 1, 2013

Keywords provided by Johann Wolfgang Goethe University Hospital:
chronic granulomatous disease

Additional relevant MeSH terms:
Granulomatous Disease, Chronic
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases processed this record on April 28, 2017