Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06647979
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-11
Brief Title:
Hematopoietic Stem Cell BCL11A Enhancer Gene Editing for Severe Β-Hemoglobinopathies
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Pilot and Feasibility Trial Hematopoietic Stem Cell BCL11A Enhancer Gene Editing for Severe Β-Hemoglobinopathies
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
A promising approach for the treatment of genetic diseases is called gene therapy Gene therapy is a relatively new field of medicine that uses genetic material mostly DNA from the patient to treat his or her own disease In gene therapy the investigators introduce new genetic material in order to fix or replace a diseased gene with the goal of curing the disease The procedure is similar to a bone marrow transplant in that the patients malfunctioning blood stem cells are reduced or eliminated using chemotherapy but it is different because instead of using a different persons donor blood stem cells for the transplant the patients own blood stem cells are given back after the new genetic material has been introduced into those cells This approach has the advantage of eliminating any risk of Graft-Versus-Host Disease GVHD reducing the risk of graft rejection and may also allow less chemotherapy to be utilized for the conditioning portion of the transplant procedure The method used to fix or replace a diseased gene is called gene editing A persons own cells are edited using a specialized biological medicine that has been formulated for use in human beings
Fetal hemoglobin HbF is a healthy non-sickling kind of hemoglobin Investigators have recently discovered a gene called BCL11A that is very important in the control of fetal hemoglobin expression Increasing the expression of this gene in sickle cell patients could increase the amount of fetal hemoglobin while simultaneously reducing the amount of sickle hemoglobin in their blood and therefore potentially cure the condition
Fetal hemoglobin HbF is a healthy non-sickling kind of hemoglobin Investigators have recently discovered a gene called BCL11A that is very important in the control of fetal hemoglobin expression Increasing the expression of this gene in sickle cell patients could increase the amount of fetal hemoglobin while simultaneously reducing the amount of sickle hemoglobin in their blood and therefore potentially cure the condition
Detailed Description:
This is a non-randomized single center open-label pilot safety and feasibility study involving a single infusion of autologous bone marrow derived CD34 hematopoietic stem cells HSPCs electroporated with BCL11A enhancer targeting Cas9 ribonucleoprotein Accrual will be a maximum of 14 evaluable subjects with sickle cell disease SCD or β-thalassemia The study will enroll 7 evaluable subjects within each disease group SCD and β-thalassemia The study will have two strata within each diagnosis group
SCD
Ages 18-40 years Stratum 1a n3-7
Ages 13-18 years Stratum 2a n0-4
β-thalassemia
Ages 18-40 years Stratum 1b n3-7
Ages 13-18 years Stratum 2b n0-4
After meeting eligibility criteria patients will be enrolled Patients with SCD will receive blood transfusions for a period of 3 months prior to hematopoietic stem cell collection with a goal of achieving a Hemoglobin S HbS level of 30 by the time of mobilization All patients will undergo peripheral stem cell mobilization and have their cells collected by apheresis The collected ells of each subject will be split into 2 portions one portion for transduction with the lentiviral vector and one portion set aside as a back-up product in the event a rescue treatment is needed Patients may undergo multiple rounds of collection if sufficient numbers of cells are not obtained with the first collection
Patients will undergo a standard work-up for autologous bone marrow transplantation prior to proceeding with conditioning and infusion of their gene-edited cells Patients will receive myeloablative conditioning with busulfan administered on days -5 to -2 prior to the infusion of edited cells The edited cells will be infused intravenously
Patients will be followed for 24 months after the infusion of their gene edited cells
SCD
Ages 18-40 years Stratum 1a n3-7
Ages 13-18 years Stratum 2a n0-4
β-thalassemia
Ages 18-40 years Stratum 1b n3-7
Ages 13-18 years Stratum 2b n0-4
After meeting eligibility criteria patients will be enrolled Patients with SCD will receive blood transfusions for a period of 3 months prior to hematopoietic stem cell collection with a goal of achieving a Hemoglobin S HbS level of 30 by the time of mobilization All patients will undergo peripheral stem cell mobilization and have their cells collected by apheresis The collected ells of each subject will be split into 2 portions one portion for transduction with the lentiviral vector and one portion set aside as a back-up product in the event a rescue treatment is needed Patients may undergo multiple rounds of collection if sufficient numbers of cells are not obtained with the first collection
Patients will undergo a standard work-up for autologous bone marrow transplantation prior to proceeding with conditioning and infusion of their gene-edited cells Patients will receive myeloablative conditioning with busulfan administered on days -5 to -2 prior to the infusion of edited cells The edited cells will be infused intravenously
Patients will be followed for 24 months after the infusion of their gene edited cells
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