Gene Therapy for X Linked Severe Combined Immunodeficiency

Gene Therapy Clinical Trial

Official title:

Gene Therapy for X Linked Severe Combined Immunodeficiency

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04286815
• Other study ID #: CHCMU gene therapy
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2020
• Est. completion date: May 1, 2025

Study information

• Verified date: March 2020
• Source: Children's Hospital of Chongqing Medical University
• Contact: Xiaodong Zhao, PHD
• Phone: 18623070626
• Email: zhaoxd530[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Gene Therapy
• Immunologic Deficiency Syndromes
• Severe Combined Immunodeficiency
• X-Linked Combined Immunodeficiency Diseases

Intervention

Device:
• Lentiviral Vector Gene Therapy
Lentiviral vector to transfer IL2RG complementary DNA to patients'bone marrow stem cells

Locations

Country	Name	City	State
China	Children's Hospital of Chongqing Medical University	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital of Chongqing Medical University

Country where clinical trial is conducted

China, 

References & Publications (3)

De Ravin SS, Wu X, Moir S, Anaya-O'Brien S, Kwatemaa N, Littel P, Theobald N, Choi U, Su L, Marquesen M, Hilligoss D, Lee J, Buckner CM, Zarember KA, O'Connor G, McVicar D, Kuhns D, Throm RE, Zhou S, Notarangelo LD, Hanson IC, Cowan MJ, Kang E, Hadigan C, Meagher M, Gray JT, Sorrentino BP, Malech HL, Kardava L. Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency. Sci Transl Med. 2016 Apr 20;8(335):335ra57. doi: 10.1126/scitranslmed.aad8856. Erratum in: Sci Transl Med. 2016 Jun 1;8(341):341er5. — View Citation

Hacein-Bey-Abina S, Hauer J, Lim A, Picard C, Wang GP, Berry CC, Martinache C, Rieux-Laucat F, Latour S, Belohradsky BH, Leiva L, Sorensen R, Debré M, Casanova JL, Blanche S, Durandy A, Bushman FD, Fischer A, Cavazzana-Calvo M. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2010 Jul 22;363(4):355-64. doi: 10.1056/NEJMoa1000164. — View Citation

Mamcarz E, Zhou S, Lockey T, Abdelsamed H, Cross SJ, Kang G, Ma Z, Condori J, Dowdy J, Triplett B, Li C, Maron G, Aldave Becerra JC, Church JA, Dokmeci E, Love JT, da Matta Ain AC, van der Watt H, Tang X, Janssen W, Ryu BY, De Ravin SS, Weiss MJ, Youngblood B, Long-Boyle JR, Gottschalk S, Meagher MM, Malech HL, Puck JM, Cowan MJ, Sorrentino BP. Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1. N Engl J Med. 2019 Apr 18;380(16):1525-1534. doi: 10.1056/NEJMoa1815408. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	3-year survival rate	3-year survival rate of 10 recruited patients	three years after gene therapy of last recruited patient
Primary	5-year survival rate	5-year survival rate of 10 recruited patients	five years after gene therapy of last recruited patient
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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