Actively Recruiting
An Adaptive Design Basket Trial of Hematopoietic Stem Cell BCL11A Enhancer Gene Editing for Severe Beta-Hemoglobinopathies
Led by Daniel Bauer · Updated on 2026-02-03
10
Participants Needed
1
Research Sites
104 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
This research aims to evaluate gene therapy using gene editing for severe beta-hemoglobinopathies like sickle cell disease and transfusion-dependent beta-thalassemia. The study focuses on introducing new genetic material into a patient's own blood stem cells to fix or replace defective genes, potentially increasing healthy fetal hemoglobin and reducing sickle hemoglobin. This trial is a phase 1 pilot safety and feasibility study led by Daniel Bauer to explore this innovative treatment approach. Participants will receive a single infusion of their own bone marrow-derived CD34+ blood stem cells that have been edited targeting the BCL11A gene enhancer using a specialized Cas9 gene editing tool. Before infusion, patients undergo chemotherapy conditioning with busulfan to prepare the body. Stem cells are collected by apheresis after mobilization, with some reserved as backup. The study enrolls subjects aged 13 to 40 years with sickle cell disease or beta-thalassemia, grouped by age strata and diagnosis. During the 24-month follow-up, participants will have regular assessments including blood counts, hemoglobin levels, and monitoring for sickle cell complications like acute chest syndrome and stroke. Quality of life and safety outcomes such as serious adverse events and malignancies will also be tracked. The primary outcome is engraftment of the gene-edited cells by 42 days post-infusion. Continuous monitoring ensures participant safety and collects data on treatment impact over time.
CONDITIONS
Brief 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 specific genotypes or transfusion-dependent beta-thalassemia
- Age between 13 and 40 years
- Clinically severe disease with defined complications for sickle cell or transfusion needs for beta-thalassemia
- 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 70% or higher
- Serum creatinine at or below 1.5 times upper limit of normal and adequate kidney function
- Direct bilirubin 2.0 mg/dL or less
- Lung function tests (DLCO, FEV1, FVC) greater than 50% predicted
- Heart function with ejection fraction above 40% or shortening fraction above 25%
- Failure of hydroxyurea therapy or intolerance if applicable
- Confirmed diagnosis by genetic testing
- No suitable bone marrow donor available
- Signed informed consent
- Willing to return for follow-up for 15 years
You will not qualify if you...
- Uncontrolled infections or active malignancy
- Active complications making participation risky
- Major surgery within past 30 days
- Medical, psychiatric, or social issues limiting compliance
- Contraindication to busulfan chemotherapy
- Previous hematopoietic stem cell transplant
- Myelodysplastic syndrome or certain genetic mutations in bone marrow
- Severe cerebral vasculopathy or stroke history in sickle cell patients
- Chronic transfusion for stroke prevention
- Severe iron overload
- Positive tests for HIV, HCV, HBV, or HTLV
- Acute hepatitis or severe liver fibrosis
- Recent investigational drug or procedure within 90 days
- Pregnancy, breastfeeding, or inadequate contraception
- Inability to comply with study procedures
- Carrying a specific genetic variant (rs114518452) that excludes participation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 3 months
Participants with sickle cell disease receive blood transfusions to reduce Hemoglobin S levels before stem cell collection.
Periodic visits for transfusions over 3 months
Duration - Up to 2 weeks
Participants undergo mobilization and apheresis to collect hematopoietic stem cells, with possible multiple collection sessions if needed.
1 to 2 visits depending on collection success
Duration - Up to 1 week
Participants receive myeloablative conditioning chemotherapy followed by infusion of gene-edited stem cells.
Daily visits for conditioning over 4 days, plus 1 infusion visit
Duration - 24 months
Participants are monitored for engraftment, safety, and long-term outcomes after infusion.
Regular visits throughout 24 months for assessments
Trial Site Locations
Total: 1 location
1
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Actively Recruiting
Research Team
E
Emily Morris
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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