This study is NOT currently recruiting participants.
Number
15-I-0008
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
Yes
Population Exclusion(s)
Female
Keywords
Gene Therapy
Recruitment Keyword(s)
None
Condition(s)
Chronic Granulomatous Disease
Investigational Drug(s)
GlXCGD (pCCLChimGp9l/VSVg lentiviral vector)
Investigational Device(s)
Intervention(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.
Objectives:
- To see if a procedure called gene transfer helps people with XCGD.
Eligibility:
- People age 2-65 with XCGD with no matched donor after 1-3 months of searching.
Design:
- 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.
--Back to Top--
INCLUSION CRITERIA: 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 EXCLUSION CRITERIA: 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.
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
EXCLUSION CRITERIA:
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.
Principal Investigator
Referral Contact
For more information: