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.
Who can participate
Age range
13 Years – 40 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Diagnosis of either a) sickle cell disease with genotype HbSS, HbS/B0 thalassemia, HbSD, or HbSO
. Age 13-40 years.
. Clinically severe disease, defined as: 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.
. Adequate hematologic parameters including:
. Adequate organ function and performance status:
. Karnofsky performance status ≥70%
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This is a Phase 1 trial that hasn't started recruiting yet — does that mean the main goal right now is checking safety rather than proving it works, and what does that mean for me if I'm considering it?
2Since the trial is focused on gene editing of my own stem cells by targeting the BCL11A enhancer, can you walk me through what the collection, editing, and re-infusion process would actually involve and how long I'd likely be in the hospital?
3The primary outcome being measured is 'primary engraftment' — can you explain what that means in plain terms, and what happens if my body doesn't engraft the edited cells properly?
4Because this trial isn't recruiting yet, what is the realistic timeline before it might open, and in the meantime, are there approved treatments like hydroxyurea or existing gene therapies I should be considering right now?
5Given that this targets HbSS or HbSβ-thalassemia0 specifically, how would my doctor determine whether my exact form of sickle cell disease makes me a potentially suitable candidate to even discuss with the research team when the trial does open?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
. Serum creatinine \</=1.5 times the upper limit of normal for age, and calculated creatinine clearance or GFR \</= 60 mL/min/1.73 m2.
. Direct bilirubin ≤ 2.0 mg/dL
Exclusion criteria
. Subjects who have concomitant condition or illness including, but not limited to:
. Uncontrolled infection, such as current febrile illness, infection requiring parenteral antibiotics, or systemic fungal infection.
. Active malignancy.
. Active complication of underlying hemoglobinopathy that would place the patient at unacceptable risk for participation, in the judgment of the Investigators.
. Major surgery in the past 30 days.
. Medical/psychiatric illness/social situations that would limit compliance with study requirements as determined by the treating physician.
. Severe cerebral vasculopathy (defined by occlusion or stenosis in the circle of Willis; or presence of Moyamoya disease)
. Receiving a chronic transfusion regimen for primary or secondary stroke prophylaxis. (Note: patients with a history of abnormal transcranial Doppler (TCD) who have transitioned from transfusions to hydroxyurea for stroke prophylaxis are also not eligible for the study. Most recent TCD must be within one year of screening for patients up to 16 years old.)