NCT00394316

Gene Therapy for Chronic Granulomatous Disease

Terminated EARLY_PHASE1 Last updated 5 July 2018

What this trial tests

EARLY_PHASE1 trial testing Phagocyte Oxidase Subunit Transduced CD34 Hematopoietic Stem Cells in Chronic Granulomatous Disease in 3 participants. Terminated before completion.

Timeline

30 October 2006

Primary endpoint
8 April 2014

8 April 2014

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	EARLY_PHASE1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	3
Start date	30 October 2006
Primary completion	8 April 2014
Estimated completion	8 April 2014
Sites	1 location across United States

Drugs / interventions tested

• Phagocyte Oxidase Subunit Transduced CD34 Hematopoietic Stem Cells — full drug profile →

Conditions studied

• Chronic Granulomatous Disease — all drugs for Chronic Granulomatous Disease →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 3 to 55, male only, with Chronic Granulomatous Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

X-linked Chronic Granulomatous Disease (CGD) is an inherited disorder caused by an abnormal gene that fails to make the protein known as gp91 phox. This protein is part of a group of proteins that work to create hydrogen peroxide in neutrophils. Neutrophils are a type of white blood cell that helps fight infections. As a result, patients who do not make this gp91 phox frequently develop life-threatening infections. In addition, these neutrophils often act abnormally, resulting in the creation of a granuloma, which is an abnormal collection of cells. These granulomas can then become large enough to block organs, such as the bladder and/or intestines, causing significant problems. Patients are usually treated with antibiotics (often needed for extended periods of time) for the infections caused by CGD, and with corticosteroids for the granulomas. However, these drugs do not cure CGD itself, and can have significant side effects. Thus patients with CGD do not have a normal life expectancy.

The only available cure to date for CGD is Bone Marrow Transplantation (BMT), where the blood-making cells from a specially matched brother or sister donor (allogeneic) or a similarly matched unrelated donor are given to the patient after the patient has undergone some kind of chemotherapy or radiation in preparation for receiving the cells. If the cells from the donor engraft (or survive in the marrow), the patient can be cured; however, there is a risk that the cells may not engraft or that they may later get rejected from the body. Also, the cells from the donor can react against the patient, causing a serious disorder called "Graft Versus Host Disease" (GVHD). Although there are a number of methods used to try to reduce and/or prevent graft rejection and/or GVHD, these complications can still occur even with the newer methods now being developed. The risks of such complications are lower when a brother or sister is used as the donor; however, not all patients (even those with siblings) will have an ideally matched donor. Hence, transplantation, especially when using an unrelated donor, is not always a perfect cure.

Because the gene responsible for making the gp91 phox is known, it is possible to use gene therapy to try to cure this disease. In gene therapy, some of the blood-making cells are taken from the patient using a technique called apheresis. The normal gene is placed into the cells using special viruses called retroviruses. The cells are then able to produce the normal protein. In this trial, the patient will receive a small dose of chemotherapy called busulfan, lower than what is traditionally used in allogeneic BMT, and the newly corrected cells will then be put back into the patient.

Even with the best standard of care, a number of patients with CGD will still die from infection. For those patients who have an unresponsive or progressive infection and do not have a possible sibling donor, their only hope is either a Matched Unrelated Donor (MUD) transplant, which has a high risk of causing death itself, or gene therapy. Hence, we would propose using gene therapy in these patients as this has less risk of causing death, but can still possibly offer a cure. Even if the corrected cells do not remain life long to rid the patients entirely of their disease, as long as they persist for even a few months, they would be able to at least clear the current infection for which the patients are being considered for enrollment in this protocol. Further, they would still be eligible to undergo a matched unrelated donor transplant in the event that gene therapy does not confer any benefit.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Retrovirus gene therapy for X-linked chronic granulomatous disease can achieve stable long-term correction of oxidase activity in peripheral blood neutrophils.
   Kang EM, Choi U, Theobald N, Linton G, et al · · 2010 · cited 118× · PMID 19965657 · DOI 10.1182/blood-2009-05-222760
2. A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders.
   Tucci F, Galimberti S, Naldini L, Valsecchi MG, et al · · 2022 · cited 109× · PMID 35288539 · DOI 10.1038/s41467-022-28762-2
3. Primary Immune Deficiency Treatment Consortium (PIDTC) report.
   Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, et al · · 2014 · cited 35× · PMID 24139498 · DOI 10.1016/j.jaci.2013.07.052
4. Genetic Engineering and Manufacturing of Hematopoietic Stem Cells.
   Wang X, Rivière I. · · 2017 · cited 19× · PMID 28480310 · DOI 10.1016/j.omtm.2017.03.003
5. Gene Therapy for Primary Immunodeficiency.
   Houghton BC, Booth C. · · 2021 · cited 10× · PMID 33403354 · DOI 10.1097/hs9.0000000000000509
6. Gene therapy for inborn errors of immunity: past progress, current status and future directions.
   Torrance R, Orf K, Fox TA. · · 2025 · PMID 41693912 · DOI 10.20517/rdodj.2025.42