Granulomatous Disease, Chronic, X-linked, VariantPhase 1/2NCT01381003
Lentiviral Gene Therapy for X-Linked Chronic Granulomatous Disease (X-CGD)
A Phase 1/2 study testing pCCLchimGp91s lentiviral vector transduced CD34+ cells infusion in people with Granulomatous Disease, Chronic, X-linked, Variant, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 30 years, men only
- Conditions the study is for
- Granulomatous Disease, Chronic, X-linked, Variant
- What is being tested?
- pCCLchimGp91s lentiviral vector transduced CD34+ cells infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2011to Nov 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Great Ormond Street Hospital for Children NHS Trust
London, London, WC1N 3JH
About this study
Official title: Phase I/II Gene Therapy Protocol for X-Linked Chronic Granulomatous Disease
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.
- Being tested
- pCCLchimGp91s lentiviral vector transduced CD34+ cells infusion
- Keywords
- Chronic Granulomatous Disease, Gene therapy, X-CGD, NADPH-oxidase, gp91-phox
- Medical subject headings
- Granulomatous Disease, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pCCLchimGp91s lentiviral vector transduced CD34+ cells infusionGenetic
pCCLchimGp91s lentiviral vector transduced CD34+ cells will be infused in a volume of 50-100 mls intravenously over 30-45 minutes
| Study group | Role | What they receive |
|---|---|---|
| pCCLchimGp91s lentiviral vector transduced CD34+ cells | Experimental | pCCLchimGp91s lentiviral vector transduced CD34+ cells will be infused in a volume of 50-100 mls intravenously over 30-45 minutes Receives: Genetic: pCCLchimGp91s lentiviral vector transduced CD34+ cells infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival following gene therapy
Measured: 3 years follow up
Secondary outcomes (2)
Reduction in frequency of infections
Measured: evaluated from 1st year after treatment by clinical history, complete physical examination, haematological and microbiological tests
Long term immune reconstitution
Measured: 3 years follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2011 (estimated)
- Study startNov 2011
- Primary completionNov 2016 (estimated)
- Study completionNov 2016 (estimated)
Why it stopped: Study is withdrawn before recruting participants, new trial will be multi centre, sponsored by different organisation.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Granulomatous Disease, Chronic, X-linked, VariantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Investigators
- Adrian Thrasher, Professor, Principal investigator, Great Ormond Street Hospital for Children NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01381003
- Sponsor's protocol ID
- 11-MI-03
- Status last verified
- Jun 2012
- First submitted
- 23 Jun 2011
- Last updated
- 4 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Gene Therapy Protocol for X-Linked Chronic Granulomatous Disease
- ClinicalTrials.gov ID
- NCT01381003
- Acronym / sponsor ID
- 11-MI-03
- Keywords
- Chronic Granulomatous Disease, Gene therapy, X-CGD, NADPH-oxidase, gp91-phox
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study is withdrawn before recruting participants, new trial will be multi centre, sponsored by different organisation.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation TrustUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Nov 2016 (estimated)
- Study completion
- Nov 2016 (estimated)
- First posted
- 27 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| pCCLchimGp91s lentiviral vector transduced CD34+ cells | Experimental | Genetic: pCCLchimGp91s lentiviral vector transduced CD34+ cells infusionpCCLchimGp91s lentiviral vector transduced CD34+ cells will be infused in a volume of 50-100 mls intravenously over 30-45 minutes |
Who may qualify
- Ages
- Up to 30 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pCCLchimGp91s lentiviral vector transduced CD34+ cells infusionpCCLchimGp91s 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 |
Primary outcome
Overall survival following gene therapy
Time frame: 3 years follow up
2 secondary outcomes
Reduction in frequency of infections
Time frame: evaluated from 1st year after treatment by clinical history, complete physical examination, haematological and microbiological tests
Long term immune reconstitution
Time frame: 3 years follow up
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2012.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adrian Thrasher, Professor principal investigator
Great Ormond Street Hospital for Children NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing pCCLchimGp91s lentiviral vector transduced CD34+ cells infusion in people with Granulomatous Disease, Chronic, X-linked, Variant, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 4 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival following gene therapy (time frame: 3 years follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2012.