Actively Recruiting
Hematopoietic Stem Cell BCL11A Enhancer Gene Editing for Severe β-Hemoglobinopathies
Led by Daniel Bauer · Updated on 2026-02-03
10
Participants Needed
1
Research Sites
260 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Hematopoietic Stem Cell BCL11A Enhancer Gene Editing for Severe β-Hemoglobinopathies
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Diagnosis of sickle cell disease with genotypes HbSS, HbS/B0 thalassemia, HbSD, or HbSO, or transfusion-dependent beta-thalassemia
- Age between 13 and 40 years
- Clinically severe disease: For sickle cell disease, at least two acute chest syndrome episodes or three severe pain events requiring medical care in the past 2 years; for beta-thalassemia, at least 100 mL/kg/year or 10 units/year of blood transfusions in the past 2 years
- White blood cell count between 2.5 and 25.0 x 10^9/L
- Platelet count between 150 and 700 x 10^9/L
- Karnofsky performance status of 70% or higher
- Serum creatinine less than or equal to 1.5 times the upper normal limit, and creatinine clearance or GFR of at least 60 mL/min/1.73 m^2
- Direct bilirubin less than or equal to 2.0 mg/dL
- Lung function (DLCO corrected for hemoglobin, FEV1, FVC) over 50% of predicted
- Left ventricular ejection fraction over 40% or shortening fraction over 25%
- For sickle cell patients, failure of hydroxyurea therapy or intolerance unless not indicated; hydroxyurea to be stopped before transfusions begin
- Confirmed diagnosis by molecular genetic testing
- No HLA-identical related bone marrow donor available
- Signed informed consent
- Willingness to return for follow-up for 15 years
You will not qualify if you...
- Uncontrolled infections such as febrile illness or infections needing intravenous antibiotics
- Active cancer
- Active complications of hemoglobinopathy posing unacceptable risk
- Major surgery within the past 30 days
- Medical, psychiatric, or social conditions limiting study compliance
- Contraindication to busulfan
- Previous hematopoietic stem cell transplant
- Bone marrow findings of myelodysplastic syndrome or pathogenic mutations related to blood cancers
- For sickle cell patients: severe cerebral vasculopathy, chronic transfusion for stroke prevention, history of overt stroke or neurologic events over 24 hours
- Severe iron overload per investigator judgment
- Positive tests for HIV, HCV, HBV, or HTLV
- Acute hepatitis or significant liver fibrosis/cirrhosis
- Receipt of investigational drugs or procedures within 90 days
- Pregnancy, breastfeeding, or inadequate contraception in fertile subjects
- Noncompliance risk as judged by investigators
- Presence of cytosine allele at SNP rs114518452 genetic site
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Actively Recruiting
Research Team
E
Emily Morris
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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