Lentiviral Gene Therapy for X-Linked Chronic Granulomatous Disease (X-CGD)

This study has been withdrawn prior to enrollment.
(Study is withdrawn before recruting participants, new trial will be multi centre, sponsored by different organisation.)
Sponsor:
Information provided by:
Great Ormond Street Hospital for Children NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01381003
First received: June 23, 2011
Last updated: June 1, 2012
Last verified: June 2012
  Purpose

Chronic Granulomatous Disease (CGD) is a rare inherited disorder in which patients suffer from severe infection and inflammation. The first indication of disease usually appears in early childhood. The basic defect found to be lie in specialised white blood cells called phagocytic cells, which are responsible for engulfing and destroying germs. In CGD, there is a defect in an enzyme (known as NADPH-oxidase) that is responsible for generating bleach like substances that are important for killing some important germs. In the form of the disease known as X-CGD (which accounts for two thirds of patients), there are defined mistakes in a gene called gp91-phox, which is a key part of the NADPH-oxidase.

In many cases, patients can be protected from infection by constant intake of antibiotics. However, in others potential life-threatening infections break through. In some cases patients also develop serious inflammation requiring high doses of drugs such as steroids. CGD can be cured by bone marrow transplant, but the best results are available when there is matched donor available. Transplant from unmatched donor have a much worse outcome.

Gene therapy of CGD can be performed by introducing a normal copy of human gp91-phox gene into the blood forming stem cells of patients' bone marrow by using a gene carrier (in this study called lentiviral vector). After treatment of the bone marrow cells in a specialised laboratory are given back to the patient and will grow into functional phagocytic cells.


Condition Intervention Phase
Granulomatous Disease, Chronic, X-linked, Variant
Genetic: pCCLchimGp91s lentiviral vector transduced CD34+ cells infusion
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Gene Therapy Protocol for X-Linked Chronic Granulomatous Disease

Resource links provided by NLM:


Further study details as provided by Great Ormond Street Hospital for Children NHS Foundation Trust:

Primary Outcome Measures:
  • Overall survival following gene therapy [ Time Frame: 3 years follow up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Reduction in frequency of infections [ Time Frame: evaluated from 1st year after treatment by clinical history, complete physical examination, haematological and microbiological tests ] [ Designated as safety issue: No ]
  • Long term immune reconstitution [ Time Frame: 3 years follow up ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: November 2011
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pCCLchimGp91s lentiviral vector transduced CD34+ cells
pCCLchimGp91s lentiviral vector transduced CD34+ cells will be infused in a volume of 50-100 mls intravenously over 30-45 minutes
Genetic: pCCLchimGp91s lentiviral vector transduced CD34+ cells infusion
pCCLchimGp91s lentiviral vector transduced CD34+ cells will be infused in a volume of 50-100 mls intravenously over 30-45 minutes

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • History of at least one severe infection requiring hospitalisation despite standard antimicrobial prophylaxis and/or inflammation complications including one of the following: Oesophageal obstruction, gastric outlet obstruction, bladder outlet obstruction or colitis
  • Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or significantly reduced biochemical activities of the NADPH-oxidase
  • Parental/Guardian and where appropriate Child's signed consent/assent

Exclusion Criteria:

  • 10/10 HLA identical (A,B,C,DR,DQ) family or unrelated or cord blood donor unless there is deemed to be an unacceptable risk associated with an allogeneic procedure
  • Contraindication for leukapheresis (anaemia Hb <8g/dl, cardiovascular instability, severe coagulopathy) or for administration of conditioning medication
  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 ClinicalTrials.gov identifier: NCT01381003

Locations
United Kingdom
Great Ormond Street Hospital for Children NHS Trust
London, United Kingdom, WC1N 3JH
Sponsors and Collaborators
Great Ormond Street Hospital for Children NHS Foundation Trust
Investigators
Principal Investigator: Adrian Thrasher, Professor Great Ormond Street Hospital for Children NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Biren Patel, Great Ormond Street Hospital for Children NHS Trust
ClinicalTrials.gov Identifier: NCT01381003     History of Changes
Other Study ID Numbers: 11-MI-03
Study First Received: June 23, 2011
Last Updated: June 1, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Great Ormond Street Hospital for Children NHS Foundation Trust:
Chronic Granulomatous Disease
Gene therapy
X-CGD
NADPH-oxidase
gp91-phox

Additional relevant MeSH terms:
Chronic Disease
Granuloma
Granulomatous Disease, Chronic
Disease Attributes
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hematologic Diseases
Immune System Diseases
Immunologic Deficiency Syndromes
Leukocyte Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Pathologic Processes
Phagocyte Bactericidal Dysfunction

ClinicalTrials.gov processed this record on October 29, 2014