An Adaptive Design Basket Trial of Hematopoietic Stem Cell BCL11A Enhancer Gene Editing for Severe β-Hemoglobinopathies
Daniel Bauer
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 patient's malfunctioning blood stem cells are reduced or eliminated using chemotherapy, but it is different because instead of using a different person's (donor) blood stem cells for the transplant, the patient's 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 person's 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.
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 (n=3-7) Ages ≥13-18 years: Stratum 2a (n=0-4) β-th…
Eligibility
- Age range
- 13–40 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Diagnosis of either a) sickle cell disease with genotype HbSS, HbS/B0 thalassemia, HbSD, or HbSO, or b) transfusion-dependent β-thalassemia 2. Age 13-40 years. 3. Clinically severe disease, defined as: For sickle cell disease, the presence of one or more of the following clinical complications: i) Minimum of two episodes of acute chest syndrome (ACS) in the 2 years before study entry. ii) History of three or more episodes of severe pain events requiring a visit to a medical facility and treatment with parenteral opioids in the 2 years before study entry. For β-thalassem…
Interventions
- Biologicalautologous bone marrow derived CD34+ HSPCs electroporated with BCL11A enhancer targeting Cas9 ribonucleoprotein
autologous bone marrow derived CD34+ HSPCs electroporated with BCL11A enhancer targeting Cas9 ribonucleoprotein
- DeviceSequencing Assay for Variant rs114518452
Device used to carry out the diagnostic testing for exclusion criteria number 12
Location
- Boston Children's HospitalBoston, Massachusetts