Gene Transfer for Sickle Cell Disease

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen byErica Esrick, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: David Williams

No Placebo Group

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

This trial is for people aged 3-40 with severe Sickle Cell Disease (SCD) who've had multiple pain events, acute chest syndrome, or need chronic transfusions. They must have tried hydroxyurea without success and can't have a matching bone marrow donor. Participants should be in stable health otherwise and willing to follow up for 15 years.

Inclusion Criteria

I am between 3 and 40 years old.

Parental/guardian/patient signed informed consent

Willingness to return for follow-up for 15 years

+9 more

Exclusion Criteria

I cannot undergo bone marrow harvest or take certain medications due to health reasons.

Non-compliance with study procedures

Positive HIV serology or HIV nucleic acid testing, or positive serology for HCV, HBV, or HTLV

+7 more

Participant Groups

The trial tests gene therapy using the patient's own modified blood stem cells to treat SCD. It involves a single infusion of these engineered cells aiming to increase fetal hemoglobin production which could potentially cure SCD.

1Treatment groups

Experimental Treatment

Group I: Treatment armExperimental Treatment1 Intervention

open-label, non-randomized, single center, pilot and feasibility, single arm cohort study of a single infusion of autologous bone marrow derived CD34+ HSC cells transduced with lentiviral vector containing a short-hairpin RNA targeting BC11A.