Clinical trial NCT04286815: Gene Therapy for X Linked Severe Combined Immunodeficiency
Official title: Gene Therapy for X Linked Severe Combined Immunodeficiency
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Gene Therapy
Keywords: Gene Therapy
X Linked Severe Combined Immunodeficiency
Lentiviral Vector
Lead sponsor: Children's Hospital of Chongqing Medical University
Sponsor class: OTHER
First posted: 2020-02-27
Enrollment: 10
Sex: MALE
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 1-year survival rate 1-year survival rate
timeFrame: one year after gene therapy of last recruited patient
measure: 3-year survival rate
timeFrame: three years after gene therapy of last recruited patient
measure: 5-year survival rate
timeFrame: five years after gene therapy of last recruited patient
Secondary outcomes:
measure: Growth velocity after gene therapy,weight in kilograms, height in meters
timeFrame: through study completion, an average of 2 year
measure: Vector marking (vector copy number per cell) in blood and bone marrow cells
timeFrame: through study completion, an average of 1 year
measure: Absolute numbers of peripheral-blood immune-cell subsets
timeFrame: through study completion, an average of 1 year
measure: Quantity of DNA T-cell-receptor excision circles (TRECs) in peripheral-blood mononuclear cells
timeFrame: through study completion, an average of 1 year
measure: Serum immunoglobulins levels
timeFrame: through study completion, an average of 2 year
measure: Number of patients without intravenous immune globulin supplementation
timeFrame: through study completion, an average of 2 year
measure: Number of patients who has a response to vaccines
timeFrame: through study completion, an average of 2 year
measure: Number of patients who recovers from previous infection（virus and bacteria）
timeFrame: through study completion, an average of 2 year
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Children's Hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: Assistant President of Children's Hospital of Chongqing Medical University
name: Xiaodong Zhao, PHD
role: STUDY_DIRECTOR
References:
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.
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, Debre 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.
citation: 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.