Lentiviral Gene Transfer for Treatment of Children Older Than 2 Years of Age With X-Linked Severe Combined Immunodeficiency (LVXSCID-OC)
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|ClinicalTrials.gov Identifier: NCT03315078|
Recruitment Status : Recruiting
First Posted : October 19, 2017
Last Update Posted : November 29, 2018
|Condition or disease||Intervention/treatment||Phase|
|X-Linked Combined Immunodeficiency Diseases||Biological: CD34+ HSCs transduced with the lentivirus vector, VSV-G pseudotyped CL20-4i-EF1α-hγc-OPT Drug: Palifermin Drug: Busulfan||Phase 1 Phase 2|
This study will evaluate the safety and effectiveness of lentiviral gene transfer treatment at restoring immune function to participants with X-linked severe combined immunodeficiency (XSCID) who are 2 to 40 years of age, and have significant impairment of immunity. XSCID is a severe genetic condition of the immune system.
Participants in this study will be treated at the National Institutes of Health (NIH) Clinical Center.
Before the gene transfer treatment, a participant's own CD34+ hematopoietic stem cells (HSCs) will have been or will be collected from the participant's blood or bone marrow. When the participant has the required number of HSCs harvested, then the participant's HSCs will be grown in tissue culture and exposed to the lentiviral gene transfer vector containing the corrective gene (VSV-G pseudotyped CL20-4i-EF1α-hγc-OPT). These gene corrected HSCs will be administered by intravenous (IV) infusion to the participant. To increase engraftment of the corrected HSCs, participants will receive a chemotherapy drug called busulfan on 2 days before the gene transfer treatment. Participants will also receive palifermin, which helps prevent mucositis, which is the main side effect from the busulfan.
After the gene transfer treatment, participants will be monitored to see if the treatment is safe and whether their immune system improves. Participants will be followed at frequent intervals for the first 2 years, and less frequently thereafter so that the effectiveness in restoration of immune function and the safety of the treatment can be evaluated. Additional safety follow-up may occur through Year 15.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Lentiviral Gene Transfer for Treatment of Children Older Than 2 Years of Age With X-Linked Severe Combined Immunodeficiency|
|Actual Study Start Date :||April 2012|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2022|
Experimental: Gene-Modified CD34+ HSCs
Participants will receive palifermin on Days -6, -5, and -4 and then busulfan on Days -3 and -2. On Day 0, participants will undergo the gene transfer treatment with infusion of the gene-modified CD34+ HSCs. They will receive palifermin on Days 1, 2, and 3.
Biological: CD34+ HSCs transduced with the lentivirus vector, VSV-G pseudotyped CL20-4i-EF1α-hγc-OPT
Administered by intravenous (IV) infusion
Administered by IV infusion at a dose of 60 mg/kg/day
Administered by IV infusion at a dose of approximately 3 mg/kg per day
- Level of autologous transduced T-lymphocytes with functional γc [ Time Frame: Measured through Year 2 ]Defined by their appearance and expansion in peripheral blood
- Incidence of serious side effects due to lentiviral gene transfer [ Time Frame: Measured through Year 15 ]As determined by whether participants experience any grade 3 or greater toxicity that is directly attributed to the gene therapy procedure
- Distribution of integration sites of the lentiviral vector in reconstituted peripheral blood cells [ Time Frame: Measured through Year 15 ]Based on statistical analysis
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): NCT03315078
|United States, Maryland|
|Laboratory of Host Defenses (LHD), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)||Recruiting|
|Bethesda, Maryland, United States, 20892-1456|
|Contact: Suk See DeRavin, M.D., Ph.D 301-496-6772|
|Principal Investigator:||Suk See DeRavin, M.D., Ph.D||National Institute of Allergy and Infectious Diseases (NIAID)|