Gene Therapy for Thalassemia

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen byFarid Boulad, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: San Rocco Therapeutics

No Placebo Group

Trial Summary

What is the purpose of this trial?The patient has inherited ß-thalassemia major through the genes. These genes have mistakes in them, so the body cannot make normal red blood cells. Stem cells are made in the bone marrow. They are the earliest form of blood cells. This study is being done to see if the investigators can make the stem cells produce normal red blood cells and hemoglobin. The investigators do this by collecting the stem cells. The genes with mistakes are removed from the cells. These cells are then treated so they have the corrected gene for making normal hemoglobin. These treated cells are given back to the patient through an injection (shot) in the vein. This is also known as gene transfer. In order for the body to accept these cells, the patient will need to receive a low dose of a drug called busulfan. It is a drug that will prepare the body to receive the new stem cells. This study will let the investigators know: * If it is safe to give the patient the treated stem cells * If the treated stem cells will go into the bone marrow without causing side effects. Gene transfer has been used for the past five years. It has been successful in treating many blood disorders. At least 20 patients have received the type of treatment that the patient will get on this study. This treatment for B-thalassemia major was developed at Memorial Sloan Kettering (MSK). It was studied for a long time in the lab before being given to patients.

Eligibility Criteria

This trial is for adults with ß-thalassemia major who are part of a hypertransfusion program and have no HLA-matched sibling donor. They should not have severe liver or heart issues, active infections like Hepatitis B/C or HIV, diabetes, uncontrolled seizures, or be pregnant/breastfeeding. Adequate organ function and off certain treatments for three months prior to the study are required.

Inclusion Criteria

Subjects with an evaluation of cardiac function indicating normal function on MUGA scan or other methodology

As the inclusion criteria are more specific than the Lucarelli/Pesaro thalassemia pre-transplant classification, the criteria stated above will be used in lieu of the Lucarelli/Pesaro classification

Subjects with asymptomatic pulmonary function based on Lung Diffusion Testing DLCO Test DLCO ≥ 50% of predicted (corrected for hemoglobin)

+13 more

Exclusion Criteria

Definition of active Hepatitis C include: Positive HCV RNA Viral load by quantitative PCR testing Or if Negative HCV RNA viral load BUT on antiviral treatment Liver biopsy with pathologic evidence of Necrosis and inflammation around the portal areas - piecemeal necrosis or interface hepatitis or necrosis of hepatocytes and focal inflammation in the liver parenchyma, Inflammatory cells in the portal areas ('portal inflammation'), Fibrosis, with early stages being confined to the portal tracts, intermediate stages being expansion of the portal tracts and bridging between portal areas or to the central area, and late stages being frank cirrhosis characterized by architectural disruption of the liver with fibrosis and regeneration

I do not have active infections like Hepatitis B or C.

I do not have active infections like HTLV or HIV.

+7 more

Participant Groups

The trial tests if stem cells with corrected genes can safely produce normal red blood cells in patients with ß-thalassemia major. Patients' own stem cells will be modified to correct the genetic defect and then re-injected after pre-treatment with low-dose busulfan to help their body accept the new cells.

1Treatment groups

Experimental Treatment

Group I: Autologous CD34+ cells transduced with TNS9.3.55Experimental Treatment1 Intervention

An open label study using a non-myeloablative conditioning regimen of busulfan and 1 or several infusions of autologous hematopoietic stem cells transduced with a lentiviral vector encoding the human ß-globin gene.