Ignite Creation Date:
2024-05-05 @ 10:17 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001476
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
1999-11-03
Brief Title:
Gene Therapy for Chronic Granulomatous Diseases - Long-term Follow-up
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Gene Therapy Approach for Chronic Granulomatous Disease
Status:
COMPLETED
Status Verified Date:
2010-12-13
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This protocol will follow patients who participated in NIAIDs study Gene Therapy Approach for Chronic Granulomatous Diseases 95-I-0134 No further gene therapy treatments will be given under this protocol However because gene therapy is a new technology and involves a permanent change in the genetic code of some cells patients who have had this treatment require long-term health monitoring
Participants will be asked to provide updated address and telephone information and the names of two contact persons such as siblings or friends Patients will be seen about once a year at the NIH Clinical Center to provide an update on their health status and donate a small blood sample about 2 teaspoons which will be frozen and stored If a patient acquires a serious illness such as cancer his or her stored blood will be tested another of blood or tissue sample may also be requested for further study If a patient develops a medical problem that is thought possibly to be related to gene therapy the illness will be investigated The annual follow-up visits will continue indefinitely or until the patient declines to continue participation
Participants may also agree to store some of their blood future research on chronic granulomatous diseases and other medical conditions Stored samples may be labeled with a code such as a number that only the study team can link with the patient Any identifying information about the patient will be kept confidential as is permitted by law
Participants will be asked to provide updated address and telephone information and the names of two contact persons such as siblings or friends Patients will be seen about once a year at the NIH Clinical Center to provide an update on their health status and donate a small blood sample about 2 teaspoons which will be frozen and stored If a patient acquires a serious illness such as cancer his or her stored blood will be tested another of blood or tissue sample may also be requested for further study If a patient develops a medical problem that is thought possibly to be related to gene therapy the illness will be investigated The annual follow-up visits will continue indefinitely or until the patient declines to continue participation
Participants may also agree to store some of their blood future research on chronic granulomatous diseases and other medical conditions Stored samples may be labeled with a code such as a number that only the study team can link with the patient Any identifying information about the patient will be kept confidential as is permitted by law
Detailed Description:
This is a Phase III clinical trial to determine the efficacy and safety of a method of ex vivo gene therapy to treat both X-linked gp91phox deficient Chronic Granulomatous Disease CGD and autosomal recessive p47phox deficient CGD CGD is an inherited immune deficiency in which blood neutrophils and monocytes fail to produce superoxide and other antimicrobial oxidants and patients get recurrent life-threatening infections 30 CGD patients of either sex at least 5 years of age may be enrolled in addition to the 5 patients enrolled in the first phase of this trial Patients less than 16 years of age must have an active infection or a recent relapse of infection at the time of enrollment Patients may receive up to 6 cycles of stem cell mobilization for gene therapy at intervals of 4 weeks or longer For up to first 3 cycles a cycle of stem cell mobilization for gene therapy will begin with 8 daily subcutaneous injections of the combination of flt3-ligand flt3L at 50 micro gkgday plus granulocyte-macrophage colony stimulating factor GM-CSF at 5 micro gkgday for mobilization of CD34 cells For 3 or more of the cycles of mobilization of CD34 cells for gene therapy up to the maximum of 6 cycles total the mobilization will begin with 6 daily injections of granulocyte colony stimulating factor G-CSF at 10 micro gkgday On the last two or three days of marrow growth factor administration for mobilization of CD34 cells the patients will have an apheresis procedure to harvest blood mononuclear cells thus completing a cycle of mobilization and stem cell harvest CD34 progenitors will be selected from the apheresis collection using the IsolexRegistered Trademark 300i anti-CD34 monoclonal antibodymagnetic bead selection system The purified CD34 cells may either be placed directly into culture or may be cryopreserved as per standard blood bank procedure freezing in autologous serum with 10 dimethylsufoxide DMSO and stored frozen at liquid nitrogen temperature until thawed for ex vivo culture and transduction For a specific gene therapy treatment of intravenously infused gene corrected stem cells the purified CD34 stem cells collected purified and frozen from one or more cycles of mobilization will be thawed and then pooled at the time of placement into culture for transduction with the virus vector CD34 cells will be cultured in PL2417 gas permeable plastic containers that have been pre-coated with fibronectin fragment CH-296 The growth medium will be serum-free X-VIVO 10Registered Trademark supplemented with 1 human serum albumin 100 ngml flt3-ligand 50 ngml PIXY321 and 50 ngml stem cell factor SCF Cultured CD34 progenitors will be transduced on each of 3 or 4 days with either MFGS-p47phox or MFGS-gp91phox retrovirus vectors The retrovirus vectors are replication defective packaged in amphotropic envelope lines engineered with the CRIP packaging elements 5 LTR-gag-pol-3SV40polyA 5LTR-AMenv-3SV40polyA MFGS-p47phox is packaged in the murine psi-crip line while MFGS-gp91phox is packaged in the human 293-SPA line The clinical retrovirus vector supernate will be animal protein-free and serum free Safety testing for endotoxin sterility and absence of replication competent retrovirus will be performed on the retrovirus producer lines virus particle lots and transduced cells Transduced CD34 cells will be infused into the CGD patient Thus there will be a total of up to six cycles of stem cell mobilization but because the CD34 cells from one or more cycles of mobilization may be cryopreserved and then later pooled for culture to produce a single gene corrected stem cell product for infusion there may be fewer than six rounds and possibly only one round of gene therapy treatments for a patient who participates in this study Blood will be tested periodically for the appearance and persistence of neutrophils that are functionally corrected by the gene therapy The efficacy goal for this study is to allow CGD patients to produce autologous gene-corrected functionally normal NADPH oxidase positive neutrophils to a level of at least 1 in 1000 circulating neutrophils for at least four weeks This may provide clinical benefit in the form of increased host defense against an ongoing or potential infection The clinical status of patients will be monitored for any evidence of toxicity Information obtained from this study will provide information important for achieving the ultimate goal of the development of gene therapy for CGD that will be a permanent cure for this disorder
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 95-I-0134 | None | None | None |