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Gene Transfer for Sickle Cell Disease


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 his or her own disease. In gene therapy, the investigators introduce new genetic material in order to fix or replace the patient's disease 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 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 introduce the gene into the patient's own blood stem cells is to engineer and use a modified version of a virus (called a 'vector') that efficiently inserts the "correcting" genetic material into the cells. The vector is a specialized biological medicine that has been formulated for use in human beings.

The investigators have recently discovered a gene 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. In summary, the advantages of a gene therapy approach include: 1) it can be used even if the patient does not have a matched donor available; 2) it may allow a reduction in the amount of chemotherapy required to prepare the patient for the transplant; and 3) it will avoid the strong medicines often required to prevent and treat GVHD and rejection. The goal is to test whether this approach is safe, and whether using gene therapy to change the expression of this particular gene will lead to increased fetal hemoglobin production in people with sickle cell disease.

Primary Purpose
Study Type
Phase 1


Healthy Volunteers
Minimum Age
3 Years
Maximum Age
40 Years

Inclusion Criteria:

  • 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 Criteria:

  • 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

Join this Trial

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Study Stats
Protocol No.
Dayna Terrazas
  • UCLA Westwood
For Providers
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