Study of Gene Therapy Using a Lentiviral Vector to Treat X-linked Chronic Granulomatous Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 27 November 2023
• Main ID: NCT02234934
• Date of registration: 04/09/2014
• Prospective Registration: Yes
• Primary sponsor: University of California, Los Angeles
• Public title: Study of Gene Therapy Using a Lentiviral Vector to Treat X-linked Chronic Granulomatous Disease
• Scientific title: A Two-Part, Phase I/II, Non Randomized, Multicenter, Open-Label Study of G1XCGD (Lentiviral Vector Transduced CD34+ Cells) in Patients With X-Linked Chronic Granulomatous Disease
• Date of first enrolment: October 29, 2015
• Target sample size: 16
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02234934
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Donald B. Kohn, MD
• Affiliation: University of California, Los Angeles (UCLA)

• Name: Caroline Y Kuo, MD

• Name: Elizabeth Kang, MD

• Name: Caroline Y. Kuo, MD
• Affiliation: University of California, Los Angeles (UCLA)

Key inclusion & exclusion criteria

Inclusion Criteria:

(Part A & B)

- 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 NADPH-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 initial search of NMDP registries

- No co-infection with Human Immunodeficiency Virus (HIV)-1 or -2, hepatitis B virus or
hepatitis C virus, adenovirus, parvovirus B 19 or toxoplasmosis, or active infection
with CMV

- Written informed consent for adult patient, and assent for pediatric subjects seven
years or older.

- Parental/guardian and, where appropriate, child's signed consent/assent

Exclusion Criteria:

- Age < 23 months

- 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 or bone marrow harvest (anemia Hb <8g/dl,
cardiovascular instability, severe coagulopathy)

- Appropriate organ function as outlined below must be observed within 8 weeks of
entering this trial.

1. Hematologic

1. Anemia (hemoglobin < 8 g/dL).

2. Neutropenia (absolute granulocyte count <1,000/mm3)

3. Thrombocytopenia (platelet count < 150,000/mm3).

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

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

2. Infectious

a. Evidence of co-infection with HIV-1, HIV-2, hepatitis B, Hepatitis C,
adenovirus, parvovirus B19, toxoplasmosis. CMV infection is allowable as long as
the infection is under control.

3. Pulmonary

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

4. Cardiac

1. Abnormal electrocardiogram (EKG) indicating cardiac pathology.

2. Uncorrected congenital cardiac malformation with clinical symptomatology.

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

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

5. Neurologic

1. Significant neurologic abnormality by examination.

2. Uncontrolled seizure disorder.

6. Renal

1. Renal insufficiency: serum creatinine = 1.5 mg/dl, or = 3+ proteinuria.

2. Abnormal serum sodium, potassium, calcium, magnesium, phosphate at grade III
or IV by the Common Terminology Criteria for Adverse Events (CTCAE) version
4.0.

7. Hepatic/GI:

1. Serum transaminases > 5X the upper limit of normal (ULN).

2. Serum bilirubin > 2X ULN.

3. Serum glucose > 1.5x ULN.

8. Oncologic

a. Evidence of active malignant disease

9. General

1. Expected survival < 6 months

2. Major congenital anomaly

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

4. Contraindication for administration of conditioning medication. (Known
sensitivity to Busulfan)

5. Administration of gamma-interferon within 30 days before the infusion of
transduced, autologous CD34+ cells.

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

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

8. 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 study completion.

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

Part B Additional exclusion criteria:

- Patients >12 years of age at enrolment

- Patients =12 years of age with a body weight >40kg at enrolment



Age minimum: 23 Months
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Granulomatous Disease, Chronic, X-linked

Intervention(s)

Biological: Lentiviral G1XCGD Gene Therapy

Primary Outcome(s)

Measuring percentage of subjects who have = 10% oxidase positive granulocytes [Time Frame: At month 12 after transplant]

The incidence of adverse events assessed by CTCAE v4 [Time Frame: up to 2 years]

Secondary ID(s)

2P01HL073104

G1XCGD

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Heart, Lung, and Blood Institute (NHLBI)

California Institute for Regenerative Medicine (CIRM)

Genethon

Boston Children's Hospital