Gene Therapy for X Linked Severe Combined Immunodeficiency

Study Overview
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Brief Summary
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A safety and efficacy clinical study of a lentiviral vector to transfer IL2RG complementary DNA to bone marrow stem cells in ten children with genetic diagnosed X-SCID（severe combined immune deficiency ）.The ten children will be followed for 3-5 years and be evaluated by clinical characteristics, vector marking (vector copy number per cell) in blood and bone marrow cells, immune reconstitution vector insertion-site patterns and so on.

Official Title
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Gene Therapy for X Linked Severe Combined Immunodeficiency

Conditions
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Gene Therapy

Intervention / Treatment
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* Device: Lentiviral Vector Gene Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: X-SCID patients diagnosed by IL2RG single gene mutation No HLA（human leukocyte antigen） matching donor Hematopoietic stem cell transplantation failed and the time from transplantation was more than 18 months Severe and persistent refractory infections Life expectancy of > : 4 months HIV PCR in peripheral blood was negative the children and their families signed informed consent and were willing to enter the clinical trial and complete follow-up Exclusion Criteria: The patient has diagnosed with hematological malignant diseases Received chemotherapy within 3 months HIV infection or HBV（hepatitis B virus） infection The patient or his first-degree relative has developed a malignant tumor within the age of 18 or has been diagnosed with malignant tumor prone genes Although the patient with X-SCID was diagnosed as IL2RG single gene mutation , the clinical phenotype was not severe, so they could continue to wait for the donor search; Patients whose family members have no intention to continue the follow-up treatment in any link

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>a lentiviral vector to transfer IL2RG complementary DNA to bone marrow stem cells in ten children with genetic diagnosed X-SCID（severe combined immune deficiency）. | Device: Lentiviral Vector Gene Therapy<br>* Lentiviral vector to transfer IL2RG complementary DNA to patients'bone marrow stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year survival rate 1-year survival rate | 1-year survival rate of 10 recruited patients | one year after gene therapy of last recruited patient | 
| 3-year survival rate | 3-year survival rate of 10 recruited patients | three years after gene therapy of last recruited patient | 
| 5-year survival rate | 5-year survival rate of 10 recruited patients | five years after gene therapy of last recruited patient | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth velocity after gene therapy,weight in kilograms, height in meters | Body weight and height of patients will be assessed prior to (month 0) and post gene therapy,weight in kilograms, height in meters | through study completion, an average of 2 year | 
| Vector marking (vector copy number per cell) in blood and bone marrow cells | vector marking in T cells, B cells, NK cells, myeloid cells, and bone marrow progenitors. | through study completion, an average of 1 year | 
| Absolute numbers of peripheral-blood immune-cell subsets | Absolute numbers of peripheral-blood immune-cell subsets，as determined by means of standard flow cytometry | through study completion, an average of 1 year | 
| Quantity of DNA T-cell-receptor excision circles (TRECs) in peripheral-blood mononuclear cells | Quantity of DNA T-cell-receptor excision circles (TRECs) in peripheral-blood ，as determined by means of quantitative polymerase chain reaction (PCR) | through study completion, an average of 1 year | 
| Serum immunoglobulins levels | Serum immunoglobulins levels will be reported IgM（immunoglobulin M） in mg/dL Serum immunoglobulins levels will be reported IgM in mg/dL | through study completion, an average of 2 year | 
| Number of patients without intravenous immune globulin supplementation | Number of patients without intravenous immune globulin supplementation after gene therapy | through study completion, an average of 2 year | 
| Number of patients who has a response to vaccines | Number of patients who has a response to vaccines after gene therapy | through study completion, an average of 2 year | 
| Number of patients who recovers from previous infection（virus and bacteria） | Number of patients who recovers from previous infection（virus and bacteria）after gene therapy | through study completion, an average of 2 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gene Therapy, X Linked Severe Combined Immunodeficiency, Lentiviral Vector