Stem Cell Gene Therapy for Sickle Cell Disease
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|ClinicalTrials.gov Identifier: NCT02247843|
Recruitment Status : Active, not recruiting
First Posted : September 25, 2014
Last Update Posted : April 23, 2021
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Disease||Biological: βAS3-FB vector transduced peripheral blood CD34+ cells||Phase 1 Phase 2|
Sickle cell disease (SCD) affects ~90,000 people in the U.S. who suffer significant neurological, lung, and kidney damage, as well as severe chronic pain episodes that adversely impact on quality of life. While current medical therapies for SCD can reduce short-term morbidity, the inevitable progressive deterioration in organ function results in a significant decrease in quality of health with early mortality. Allogeneic hematopoietic stem cell transplant (HSCT) can benefit patients with SCD, by providing a source for life-long production of normal red blood cells. However, allogeneic HSCT is limited by the availability of well-matched donors and immunological complications, especially for the more than 80% of patients who lack an HLA-identical sibling donor. Autologous HSCT using a patient's own peripheral blood stem cells that have been corrected by transfer of a modified human beta-globin gene that inhibits polymerization of the HbS (stem cell gene therapy) may provide a better therapeutic alternative, as it would avoid the immunologic complications and donor limitations of allogeneic HSCT.
Up to 6 subjects with SCD meeting eligibility criteria for disease severity and adequacy of organ function will be enrolled.
Following informed consent, enrolled subjects will be screened to confirm full eligibility for participation. A chronic red blood cell transfusions regimen will be given prior to stem cell collection and transplant. Subjects will undergo peripheral blood stem cell collection using plerixafor mobilization and apheresis. A portion of their stem cells will be cryopreserved as "back-up," with the remaining portion used to prepare the gene-modified Final Cellular Product: autologous peripheral blood CD34+ cells transduced ex vivo by the Lenti/G-βAS3-FB lentiviral vector to express an anti-sickling (βAS3) gene. The subject will receive marrow cytoreduction with busulfan prior to infusion of the gene-modified cells. The follow-up period will include an initial 2 years of active follow-up, where the subjects will be seen at intervals of no more than 3 months, followed by offer for enrollment into a long-term follow-up study during years 3-15.
The primary objectives of the Phase I study are to assess safety and feasibility, with secondary objectives to assess efficacy (engraftment, βAS3-globin gene expression, and effects on red blood cells function and clinical hematologic and disease parameters).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Clinical Research Study of Autologous Stem Cell Transplantation for Sickle Cell Disease (SCD) Using Peripheral Blood CD34+ Cells Modified With the Lenti/G-βAS3-FB Lentiviral Vector|
|Actual Study Start Date :||December 2014|
|Estimated Primary Completion Date :||February 2022|
|Estimated Study Completion Date :||August 2022|
Experimental: βAS3-FB vector transduced peripheral blood CD34+ cells
This is a single arm study without randomization. All subjects will receive the intervention of BetaAS3 lentiviral vector-modified autologous peripheral blood stem cell transplant.
Biological: βAS3-FB vector transduced peripheral blood CD34+ cells
CD34+ from the peripheral blood of patients with sickle cell disease (SCD) are transduced ex-vivo with the Lenti/βAS3-FB lentiviral vector. The transduced cells are then infused into the patient.
Other Name: Lenti/βAS3-FB
- Evaluation of Safety [ Time Frame: up to 24 months ]
- Clinical toxicity: Absence of grade 3-4 SAEs
- Absence of replication-competent lentivirus (RCL):
- Absence of monoclonal expansion or leukoproliferative disorder from vector insertional effects: To monitor for monoclonal expansion or leukoproliferative complications, LAM-PCR will be performed.
- Event-free survival. Event-free survival will be determined for each subject over the 24 months after gene therapy. An event is defined as death or performance of an allogeneic HSCT.
- Absence of humoral immune response to novel epitopes of βAS3-globin protein
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02247843
|United States, California|
|University of California, Los Angeles (UCLA)|
|Los Angeles, California, United States, 90095|
|Study Director:||Giulia Parisi, PhD||University of California, Los Angeles|
|Principal Investigator:||Gary Schiller, MD||University of California, Los Angeles|