Gene Therapy for X Linked Severe Combined Immunodeficiency

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.

Study Overview

• Status: Recruiting
• Conditions: Gene Therapy
• Intervention / Treatment: Device: Lentiviral Vector Gene Therapy

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaodong Zhao, PhD; Phone Number: 18623070626; Email: zhaoxd530@aliyun.com
• Study Contact Backup: Name: Qiling Xu, MD; Phone Number: 18581059910; Email: 272864835@qq.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400014
      • Recruiting
      • Children's Hospital of Chongqing Medical University
      • Contact: Xiaodong Zhao, PhD; Phone Number: 18623070626; Email: zhaoxd530@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental Group; 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; Lentiviral vector to transfer IL2RG complementary DNA to patients'bone marrow stem cells

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital of Chongqing Medical University
• Investigators: Study Director: Xiaodong Zhao, PHD, Assistant President of Children's Hospital of Chongqing Medical University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2020
• Primary Completion (ANTICIPATED): May 1, 2023
• Study Completion (ANTICIPATED): May 1, 2025

Study Registration Dates

• First Submitted: February 23, 2020
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (ACTUAL): February 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 27, 2020
• Last Update Submitted That Met QC Criteria: March 26, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Gene Therapy; Lentiviral Vector; X Linked Severe Combined Immunodeficiency
• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; DNA Repair-Deficiency Disorders; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Severe Combined Immunodeficiency; X-Linked Combined Immunodeficiency Diseases
• Other Study ID Numbers: CHCMU gene therapy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No