Ignite Creation Date:
2024-05-05 @ 11:08 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001399
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
1999-11-03
Brief Title:
Gene Therapy for the Treatment of Fanconis Anemia Type C
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Retroviral Mediated Gene Transfer of the Fanconi Anemia Complementation Group C Gene to Hematopoietic Progenitors of Group C Patients
Status:
COMPLETED
Status Verified Date:
2009-02-11
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:
Fanconis Anemia is an inherited disorder that can produce bone marrow failure In addition some patients with Fanconis anemia have physical defects usually involving the skeleton and kidneys The major problem for most patients is aplastic anemia the blood counts for red blood cells white blood cells and platelets are low because the bone marrow fails to produce these cells Some patients with Fanconis anemia can develop leukemia or cancers of other organs
Many laboratory studies have suggested that Fanconis anemia is caused by an inherited defect in the ability of cells to repair DNA Recently the gene for one of the four types of Fanconis anemia type C has been identified It is known that this gene is defective in patients with Fanconis anemia type C
Researchers have conducted laboratory studies that suggest Fanconis anemia type C may be treatable with gene therapy Gene therapy works by placing a normal gene into the cells of patients with abnormal genes responsible for Fanconis anemia type C After the normal gene is in place new normal cells can develop and grow Drugs can be given to these patients kill the remaining abnormal cells The new cells containing normal genes and will not be harmed by these drugs
The purpose of this study is to test whether researchers can safely place the normal Fanconis anemia type C gene into cells of patients with the disease The gene will be placed into special cells in the bone marrow called stem cells These stem cells are responsible for producing new red blood cells white blood cells and platelets
Many laboratory studies have suggested that Fanconis anemia is caused by an inherited defect in the ability of cells to repair DNA Recently the gene for one of the four types of Fanconis anemia type C has been identified It is known that this gene is defective in patients with Fanconis anemia type C
Researchers have conducted laboratory studies that suggest Fanconis anemia type C may be treatable with gene therapy Gene therapy works by placing a normal gene into the cells of patients with abnormal genes responsible for Fanconis anemia type C After the normal gene is in place new normal cells can develop and grow Drugs can be given to these patients kill the remaining abnormal cells The new cells containing normal genes and will not be harmed by these drugs
The purpose of this study is to test whether researchers can safely place the normal Fanconis anemia type C gene into cells of patients with the disease The gene will be placed into special cells in the bone marrow called stem cells These stem cells are responsible for producing new red blood cells white blood cells and platelets
Detailed Description:
Fanconi anemia FA is a rare genetic disorder characterized by progressive pancytopenia congenital abnormalities and predisposition to malignancy Therapy is currently limited to allogeneic marrow transplantation patients lacking a suitable donor usually die from aplasia or acute leukemia Recently mutation in a novel gene named FACC Fanconi anemia C-complementing has been identified as causing one type of FA FACC mutations which introduce splicing errors or stop codons have been identified in 15 of FA patients We have recently been successful in functional complementation of four FA cell lines using retroviral vectors to transfer a copy of the normal FACC gene We also analyzed the ability of four viral vectors to functionally correct hematopoietic progenitor cells from a patient bearing a splice donor mutation As for the lymphoid cell lines these CD34 enriched cells were extremely sensitive to MMC After injection of these progenitor cells with viral vectors bearing normal FACC the progenitors gave rise to increased numbers of colonies both in the absence and presence of up to 5 nM MMC whereas control cells were completely destroyed by 1 nM MMC In summary we have demonstrated that 1 retroviral vectors can be engineered to transfer a normal FACC gene to FAC lymphoid cell lines and primary hematopoietic cells 2 introduction of a normal FACC gene into CD34 progenitors markedly enhances their growth in the absence and presence of MMC
This study is designed to determine whether hematopoietic progenitors transduced with the normal FACC gene can be re-infused safely into FAC patients CD34 cells obtained from G-CSF mobilized peripheral blood will be transduced ex vivo over a 72 hour period in the presence of IL-3 IL-6 and stem cell factor with the FACC retroviral vector These transduced cells will be re-infused into FAC patients Patients will be monitored for toxicities as well as evidence of successful gene transfer and expression The procedure will be repeated up to a total of 4 times with each treatment 2-4 months apart Theoretically these rescued stem cells should have a selective growth advantage within the hypoplastic FA marrow environment in vivo
This study is designed to determine whether hematopoietic progenitors transduced with the normal FACC gene can be re-infused safely into FAC patients CD34 cells obtained from G-CSF mobilized peripheral blood will be transduced ex vivo over a 72 hour period in the presence of IL-3 IL-6 and stem cell factor with the FACC retroviral vector These transduced cells will be re-infused into FAC patients Patients will be monitored for toxicities as well as evidence of successful gene transfer and expression The procedure will be repeated up to a total of 4 times with each treatment 2-4 months apart Theoretically these rescued stem cells should have a selective growth advantage within the hypoplastic FA marrow environment in vivo
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 |
|---|---|---|---|
| 94-H-0033 | None | None | None |