Chronic Granulomatous Disease (CGD) Gene Therapy Clinical Trial

Gene Transfer in Patients with Chronic Granulomatous Disease (CGD)

A Phase I/II Open Label Study of Gene Transfer (Lentiviral vector transduced CD34+ cells) in Patients with Chronic Granulomatous Disease (CGD)

Chronic Granulomatous Disease (CGD) is an inherited immune system disorder that affects males. It occurs when a type of white blood cell that usually helps the body fight infection, called a phagocyte, does not work properly. In CGD, the phagocytes can’t kill germs that are ingested, and so cannot protect the body from bacterial and fungal infections.

This chronic granulomatous disease (CGD) gene therapy clinical trial uses a safety-improved, third generation self-inactivating lentiviral vector to transduce CD34+ selected hematopoietic stem cells. Genetically modified cells are infused after busulfan preparative conditioning. This vector was designed to address the leukemias that have occurred in other past gene therapy trials using a gammaretroviral vector containing strong intact long-term repeat regions.

Preclinical data showed an excellent safety profile for this vector, leading to FDA approval and NHLBI-appointed DSMB approval of this trial. The costs of research aspects of the protocol will be provided for patients treated on the trial by the Gene Therapy Resource Program, NHLBI and NIH.

Inclusion criteria

• Male X-CGD patients > 23 months of age
• Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or reduction >95% of the biochemical activity of the NAHPD-oxidase
• At least one prior, ongoing or refractory severe infection and/or inflammatory complications requiring hospitalization despite conventional therapy
• No 10/10 HLA-matched donor available after search of NMDP registries
• No co-infection with Human Immunodeficiency Virus (HIV) or hepatitis B virus (HBsAg positive) or hepatitis C virus (HCV RNA positive), CMV, adenovirus, parvovirus B 19 or toxoplasmosis

Exclusion criteria

• Contraindication to stem cell collection, or to administration of conditioning medication.
• Known positive HIV serology or HIV nucleic acid testing.
• Active malignancy
• Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenetics

• Learn more about our CGD gene therapy clinical trial
• Learn more about our Gene Therapy Program