Gene Therapy for X Linked Severe Combined Immunodeficiency

Not Applicable

Recruiting

• Conditions: Gene Therapy
• Interventions: Device: Lentiviral Vector Gene Therapy

• Registration Number: NCT04286815
• Lead Sponsor: Children's Hospital of Chongqing Medical University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-23
• Study First Submitted QC: 2020-02-25
• Study First Posted: 2020-02-27
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-26
• Last Update Posted: 2020-03-27
• Study Start: 2020-05-01
• Primary Completion: 2023-05-01
• Study Completion: 2025-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental Group	Lentiviral Vector Gene Therapy	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）.

Primary Outcome Measures

Name	Time	Method
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
5-year survival rate	five years after gene therapy of last recruited patient	5-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

Secondary Outcome Measures

Name	Time	Method
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
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)
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
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
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.
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
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
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

Trial Locations

Locations (1)

Children's Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China