Gene Therapy
Conditions
Keywords
Gene Therapy, X Linked Severe Combined Immunodeficiency, Lentiviral Vector
Brief summary
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.
Interventions
DEVICELentiviral Vector Gene Therapy
Lentiviral vector to transfer IL2RG complementary DNA to patients'bone marrow stem cells
Sponsors
Children's Hospital of Chongqing Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
1. X-SCID patients diagnosed by IL2RG single gene mutation 2. No HLA（human leukocyte antigen） matching donor 3. Hematopoietic stem cell transplantation failed and the time from transplantation was more than 18 months 4. Severe and persistent refractory infections 5. Life expectancy of \> : 4 months 6. HIV PCR in peripheral blood was negative 7. the children and their families signed informed consent and were willing to enter the clinical trial and complete follow-up
Exclusion criteria
1. The patient has diagnosed with hematological malignant diseases 2. Received chemotherapy within 3 months 3. HIV infection or HBV（hepatitis B virus） infection 4. 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 5. 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; 6. Patients whose family members have no intention to continue the follow-up treatment in any link
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year survival rate 1-year survival rate | one year after gene therapy of last recruited patient | 1-year survival rate of 10 recruited patients |
| 3-year survival rate | three years after gene therapy of last recruited patient | 3-year survival rate of 10 recruited patients |
| 5-year survival rate | five years after gene therapy of last recruited patient | 5-year survival rate of 10 recruited patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantity of DNA T-cell-receptor excision circles (TRECs) in peripheral-blood mononuclear cells | through study completion, an average of 1 year | Quantity of DNA T-cell-receptor excision circles (TRECs) in peripheral-blood ，as determined by means of quantitative polymerase chain reaction (PCR) |
| Serum immunoglobulins levels | through study completion, an average of 2 year | Serum immunoglobulins levels will be reported IgM（immunoglobulin M） in mg/dL Serum immunoglobulins levels will be reported IgM in mg/dL |
| Growth velocity after gene therapy,weight in kilograms, height in meters | through study completion, an average of 2 year | Body weight and height of patients will be assessed prior to (month 0) and post gene therapy,weight in kilograms, height in meters |
| Number of patients who has a response to vaccines | through study completion, an average of 2 year | Number of patients who has a response to vaccines after gene therapy |
| Number of patients who recovers from previous infection（virus and bacteria） | through study completion, an average of 2 year | Number of patients who recovers from previous infection（virus and bacteria）after gene therapy |
| Number of patients without intravenous immune globulin supplementation | through study completion, an average of 2 year | Number of patients without intravenous immune globulin supplementation after gene therapy |
| Vector marking (vector copy number per cell) in blood and bone marrow cells | through study completion, an average of 1 year | vector marking in T cells, B cells, NK cells, myeloid cells, and bone marrow progenitors. |
| Absolute numbers of peripheral-blood immune-cell subsets | through study completion, an average of 1 year | Absolute numbers of peripheral-blood immune-cell subsets，as determined by means of standard flow cytometry |
Countries
China
Contacts
Primary ContactXiaodong Zhao, PHD
Backup ContactQiling Xu, MD
Outcome results
None listed