Status:
ACTIVE_NOT_RECRUITING
Gene Transfer for Sickle Cell Disease
Lead Sponsor:
David Williams
Conditions:
Sickle Cell Disease
Eligibility:
All Genders
3-40 years
Phase:
PHASE1
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 ...
Detailed Description
This is an open-label, non-randomized, single center, pilot and feasibility, single arm cohort study involving a single infusion of autologous bone marrow derived CD34+ HSC cells transduced with the l...
Eligibility Criteria
Inclusion
- Diagnosis of SCD with genotype HbSS, HbS/0 thalassemia, HbSD, or HbSO
- Severe symptomatic SCD, defined by the presence of one or more of the following clinical complications:
- Minimum of two episodes of acute chest syndrome (ACS) in the 2 years before study entry.
- 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.
- Recurrent priapism (\> 2 episodes) in the 2 years before study entry.
- Red-cell alloimmunization (\>2 antibodies) during long-term transfusion therapy.
- Receiving, or indicated to receive (based on prior stroke or elevated transcranial Doppler (TCD) results), chronic transfusions for primary or secondary stroke prophylaxis.
- Age 3 years to 40 years .
- Failure of hydroxyurea therapy due to lack of clinical improvement or inability to tolerate due to side effects (e.g., myelosuppression, gastrointestinal symptoms, or hepatic enzyme elevations). Clinical criteria must be met despite taking hydroxyurea for greater than or equal to 6 months, unless contraindicated or not tolerated. Patients taking hydroxyurea who still meet all inclusion criteria are eligible for the trial.
- No HLA-genotypically identical related bone marrow donor available
- Parental/guardian/patient signed informed consent
- Willingness to return for follow-up for 15 years
- White blood cell (WBC) count within the range of 3.0 - 20.0 x 109 /L Hemoglobin within the range of 5 - 11 g/dL Platelet count within the range of 100 - 600 x 109 /L PT and PTT within normal limits, unless prolonged due to anticoagulation requirement.
- Adequate organ function and performance status:
- Performance status ≥70% (Lansky play for age \<16 years, Karnofsky for age ≥16 years)
- Left ventricular ejection fraction \>40% or shortening fraction \>25%
- Direct bilirubin ≤ 2.0 mg/dL
- Serum creatinine \</= 1.5 times the upper limit of normal for age, and creatinine clearance or GFR \>/= 70 mL/min/1.73 m2.
- For ages \> 7 years, DLCO (corrected for hemoglobin), FEV1, FVC \>50% of predicted; if age \< 7 years, then oxygen saturation \>92% on room air.
Exclusion
- Contraindication to bone marrow harvest, or to administration of conditioning medication (busulfan).
- Subjects who have undergone allogeneic transplant previously.
- Known positive HIV serology or HIV nucleic acid testing, or positive serology for HCV, HBV, or HTLV.
- Uncontrolled infection.
- Active malignancy.
- Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenetics.
- Receipt of an investigational study drug or procedure within 90 days of study enrollment.
- Pregnancy, or breastfeeding in a postpartum female, or absence of adequate contraception for fertile subjects. Females of child-bearing potential must agree to use a medically acceptable method of birth control such as oral contraceptive, intrauterine device, barrier and spermicide, or contraceptive implant/injection from Screening through at least 6 months after drug product infusion. Male subjects must agree to use effective contraception (including condoms) from Screening through at least 6 months after drug product infusion.
- Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on prior biopsy.
- An assessment by the Investigators that the subject will not comply with the study procedures outlined in the study protocol
Key Trial Info
Start Date :
February 13 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
November 13 2026
Estimated Enrollment :
10 Patients enrolled
Trial Details
Trial ID
NCT03282656
Start Date
February 13 2018
End Date
November 13 2026
Last Update
January 9 2026
Active Locations (2)
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1
UCLA - Mattel Children's Hospital
Los Angeles, California, United States, 90095
2
Boston Children's Hospital
Boston, Massachusetts, United States, 02115