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This study examines a gene therapy in patients with X-linked chronic granulomatous disease (an inherited condition affecting the immune system), in which a healthy copy of the CYBB (gp91 phox) gene is delivered into the patient's own stem cells using a lentiviral vector. Patients aged 3 to 60 with a DNA-confirmed diagnosis, at least one prior severe infection, and no suitable donor may take part. The study is being conducted in Phase 1/Phase 2 and is enrolling participants by invitation.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
-INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: * Must have confirmed molecular diagnosis of X-linked CGD confirmed by deoxyribonucleic acid (DNA) sequencing and supported by laboratory evidence for absent or reduction \>90% of the biochemical activity of the NADPH-oxidase. * At least 1 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 National Marrow Donor Program (NMDP) registries within the last year. * Must weigh at least 15 kg. * Male or female, and must be at least 3 years of age but no older than 60. * Parent/guardian must be willing to sign and date informed consent form for child and where appropriate, child may sign assent. * Stated willingness to comply with all study procedures and availability for the duration of the study. * Ability to take oral medication and be willing to adhere to the prophylactic regimen. * Apheresis of patients for the hematopoietic stem cells collected as a part of this protocol will be performed according to the Standard of Care apheresis practices established in the NIH CC Department of Transfusion Medicine for such procedures. * For apheresis, pediatric patients: --Must weigh at least 15 kg body weight; --Preserved renal function (creatinine \<=2.5 mg/dL; \<=3+ proteinuria); preserved hepatic function (bilirubin \<=2.0 mg/dl); * Must be negative for co-infection with human immunodeficiency virus (HIV) or hepatitis B virus (HBsAg positive) or hepatitis C virus (HCV ribonucleic acid (RNA) positive), adenovirus, parvovirus B 19 or toxoplasmosis or mycobacterial infection (prior or current). * For females of reproductive potential, must agree to use of 2 highly effective contraception throughout study participation and for at least 3 months after the study. * For females: * Condoms, male or female, with or without a spermicide; * Diaphragm or cervical cap with spermicide; * Intrauterine device; * Contraceptive pills or patch, Norplant, Depo-Provera, or other FDA- approved contraceptive method; * For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner. * Agreement to adhere to Lifestyle Considerations throughout study duration. * Ability of subject (Patient/Legal Guardian) to understand and the willingness to sign a written informed consent document. * For the Natural History Protocol (05-I-0213): All patients must be willing to allow storage of blood samples for future studies. * Must provide a durable power of attorney (DPA) for health care decisions to an appropriate adult relative or guardian in accordance to NIH-200 "NIH Advance Directive for Health Care and Medical Research Participation." EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: * Patient/Parent/Guardian unable or unwilling to comply with the protocol requirements. * Contraindication for leukapheresis (anemia Hb \<8 g/dl, cardiovascular instability, severe coagulopathy). * Patients who are unable to lie prone during the bone marrow harvesting procedure (in the case of bone marrow harvest, contraindication to general anesthesia). * Have a 10/10 HLA identical (A,B,C,DR,DQ) family or unrelated adult donor unless there is deemed to be an unacceptable risk associated with an allogeneic procedure. * Tested positive (definitive) for the presence of multiple types (2 or more) of anti-platelet antibodies. * Altered organ function as outlined below observed within 8 weeks of entering this trial. a. Hematologic i. Anemia (hemoglobin \< 8 g/dl). ii. Neutropenia (absolute granulocyte count \<1,000/mm3 ). iii. Thrombocytopenia (platelet count \< 150,000/mm3). iv. Prothrombin Time (PT) INR or Partial thromboplastin time (PTT) \> 2 X the upper limits of normal (ULN) (patients with a correctable deficiency controlled on medication will not be excluded). v. Cytogenetic abnormalities known to be associated with hematopoietic defect on peripheral blood or bone marrow. b. Infectious i. Evidence of infection with HIV-1 and -2, Hepatitis B, Hepatitis C, adenovirus, parvovirus B 19 or toxoplasmosis within 8 weeks prior to mobilization/apheresis or bone marrow harvest. Cytomegalovirus (CMV) infection is allowable as long as the infection is under control. ii. History of infection with mycobacteria or Bacille Calmette-Guerin (BCG) vaccination. c. Pulmonary i. Resting O2 saturation by pulse oximetry \< 90% on room air. d. Cardiac i. Abnormal electrocardiogram (ECG) indicating cardiac pathology. ii. Uncorrected congenital cardiac malformation with clinical symptomatology. iii. Active cardiac disease, including clinical evidence of congestive heart failure, cyanosis, hypotension. iv. Poor cardiac function as evidenced by LV ejection fraction \<40% on echocardiogram. e. Neurological i. Significant neurologic abnormality by examination. ii. Uncontrolled seizure disorder. f. Renal i. Renal insufficiency: serum creatinine \>=2.5 mg/dl, or \>=3+ proteinuria. * Chemistry Lab abnormalities: Serum sodium \>= 156 mmol/L or \<= 129 mmol/L, potassium \>= 6.1 mmol/L or \<= 2.9 mmol/L, calcium \>= 3.2 mmol/L or \< 1.74 mmol/L , magnesium \>= 1.24 mmol/L or \< 0.39 mmol/L, phosphate \>= 5.1 mmol/L or \< 1.9 mmol/L. * Serum transaminases \> 5X the upper limit of normal (ULN). Serum bilirubin \> 2X the upper limit of normal (ULN). Serum glucose \> 1.5X the upper limit of normal (ULN). * General * Expected survival \< 6 months. * Major congenital anomaly. * Known allergic reactions to components of busulfan or dimethyl sulfoxide (DMSO) or contraindication for administration of conditioning medication. * Evidence of active malignant disease. * Treatment with another investigational drug or other intervention within 6 months. * Unable to undergo apheresis as per the NIH CC Department of Transfusion Medicine Standard of Care apheresis procedures. 1. 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. History of vasculitis. * Administration of gamma-interferon within 30 days before the infusion of transduced, autologous CD34+ cells. * 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.