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Protocol Details

A Phase I/II, Non Randomized, Multicenter, Open-Label Study of G1XCGD (Lentiviral Vector Transduced CD34+ Cells) in Patients with X-linked Chronic Granulomatous Disease (CGD)

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male
Min Age: 3
Max Age: 65

Referral Letter Required


Population Exclusion(s)



Gene Therapy

Recruitment Keyword(s)



Chronic Granulomatous Disease

Investigational Drug(s)

GlXCGD (pCCLChimGp9l/VSVg lentiviral vector)

Investigational Device(s)



Biological/Vaccine: G1XCGD (pCCLChimGp91/VSVg lentiviral vector)

Supporting Site

National Institute of Allergy and Infectious Diseases


- People with x-linked Chronic Granulomatous Disease (XCGD) have trouble fighting infections because one of their genes does not work correctly. Researchers want to understand XCGD better and treat it with a gene transfer. This takes blood stem cells and grows them with a special virus (lentivirus) to transfer the normal gene into them, then returns them to the person.


- To see if a procedure called gene transfer helps people with XCGD.


- People age 2-65 with XCGD with no matched donor after 1-3 months of searching.


- Within 3 months of beginning treatment, participants will be screened with blood tests, medical history, and physical exam. They may have dental and hearing tests, and X-rays or CT scans. A small sample of bone marrow will be taken before treatment and 12 and 24 months after treatment.

- Within 2 months of beginning treatment, participants will have their blood stem cells collected. This is done as part of a separate protocol.

- Participants will be admitted to the clinic 11-12 days before starting treatment and stay up to 6 weeks.

- An intravenous (IV) catheter will be inserted for participants who don t have one.

- Participants will have blood stem cells collected again. These will be placed in a culture with the correcting virus.

- Participants will receive chemotherapy then get their stem cells back through their IV.

- For 3 months after treatment, participants will be called weekly and visit the clinic monthly. For the next 2 years, they will visit 2 4 times a year and be called between visits.

- Blood will be collected throughout the study, including between visits.

- For years 2-15, participants will have 1-2 clinic visits a year for history, physical exam, and blood work.

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1. X-CGD patients >23 months and < 65 years of age

2. Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or reduction >70% of the biochemical activity of the NADPH-oxidase

3. At least 1 prior ongoing or refractory severe infection and/or inflammatory complications requiring hospitalization despite conventional therapy

4. No 10/10 HLA- matched donor available after initial search of NMDP registries performed within the last year.

5. Parental/guardian and where appropriate child s signed consent/assent

6. For Apheresis Collection Protocol (94-I-0073) :

a. patient must weigh at least 10 kilograms body weight

b. Preserved renal function (creatinine less than or equal to 2.5 mg/dL; less than or equal to 3+ proteinuria); preserved hepatic function (bilirubin less than or equal to 2.0 mg/dl);

c. Normal female donors of childbearing potential may be entered if using effective contraception and having a negative serum pregnancy test within one week of beginning G-CSF administration.

7. For the Natural History Protocol (05-I-0213): All patients must be willing to allow storage of blood samples for future studies.

8. Tested negative for 2 high titre anti-platelet antibodies


Patients will be excluded from the study for any of the following reasons:

- Contraindication for leukapheresis or bone marrow harvest (anemia Hb <8g/dl, cardiovascular instability, severe coagulopathy, or in the case of bone marrow harvest, contraindication to general anesthesia.)

- Patients who are unable to lie prone during the bone marrow harvesting procedure.

- Neutropenia (absolute granulocyte count <1,000/mm(3))

- Thrombocytopenia (platelet count < 150,000/mm(3))

- INR or PT or PTT > 2 times the upper limits of normal (patients with a correctable deficiency controlled on medication will not be excluded).

- Cytogenetic abnormalities known to be associated with hematopoietic defect on peripheral blood or bone marrow.

- Evidence of infection with HIV-1 and 2, hepatitis B, Hepatitis C, adenovirus, parvovirus B 19 or toxoplasmosis within 8 weeks prior to mobilization or bone marrow harvest. CMV infection is allowable as long as the infection is under control.

- Resting O2 saturation by pulse oximetry < 90% on room air.

- Abnormal electrocardiogram (EKG) indicating cardiac pathology

- Uncorrected congenital cardiac malformation with clinical symptomatology.

- Active cardiac disease, including clinical evidence of congestive heart failure, cyanosis, hypotension.

- Poor cardiac function as evidenced by LV ejection fraction < 40% on echocardiogram.

- Significant neurologic abnormality by examination.

- Uncontrolled seizure disorder.

- Renal insufficiency: serum creatinine greater than or equal to 1.5 mg/dl, or greater than or equal to 3+ proteinuria.

- Serum sodium greater than or equal to 156 mmol/L or less than or equal to 129 mmol/L , potassium greater than or equal to 6.1 mmol/L or less than or equal to 2.9 mmol/L, calcium greater than or equal to 3.2 mmol/L or less than or equal to 1.74 mmol/L , magnesium greater than or equal to 1.24 mmol/L or less than or equal to 0.39 mmol/L, phosphate greater than or equal to 5.1 mmol/L or < 1.9 mmol/L

- Serum transaminases > 5 times the upper limit of normal (ULN).

- Serum bilirubin > 2 times the upper limit of normal (ULN).

- Serum glucose > 1.5 times the upper limit of normal (ULN).

- Evidence of active malignant disease.

- Major congenital anomaly.

- Ineligible for autologous HSCT by the criteria at the clinical site.

- Contraindication for administration of conditioning medication

- Administration of gamma-interferon within 30 days before the collection of autologous CD34+ cells for tranduction

- Tested positive for the presence of anti-platelet antibodies

- Participation in another experimental therapeutic protocol within 6 months prior to baseline and during the study period

- Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study

- Patient/Parent/Guardian unable or unwilling to comply with the protocol requirements

- Unable to undergo apheresis as per Apheresis Collection Protocol (94-I-0073):

a. Patients who are hemodynamically unstable (systolic or diastolic blood pressure fall of 20 mm Hg from the stable patient s baseline measurement) or requiring mechanical respiratory assistance are excluded.

b. Female patients who are pregnant or lactating as determined by history and/or positive pregnancy test are excluded.

c. History of vasculitis or similar disorder.

-Tested positive (definitive) for the presence of multiple types (2 or more) of anti-platelet antibodies.

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Rosen FS, Cooper MD, Wedgwood RJ. The primary immunodeficiencies. N Engl J Med. 1995 Aug 17;333(7):431-40.

Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972 Nov 18;2(7786):1067-9.

Parkman R, Gelfand EW, Rosen FS, Sanderson A, Hirschhorn R. Severe combined immunodeficiency and adenosine deaminase deficiency. N Engl J Med. 1975 Apr 3;292(14):714-9.

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Principal Investigator

Referral Contact

For more information:

Elizabeth M. Kang, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 10 - CRC BG RM 6-3750
(301) 402-7567

Pamela D. Graham
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 12C103
10 Center Drive
Bethesda, Maryland 20892
(301) 451-7820

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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