Gene Therapy for X Linked Severe Combined Immunodeficiency

NCT04286815 | Unknown DMC

• 1 other identifier: CHCMU gene therapy
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Gene Therapy

Keywords

Gene Therapy; X Linked Severe Combined Immunodeficiency; Lentiviral Vector

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (8)

• Growth velocity after 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

  through study completion, an average of 1 year

• Absolute numbers of peripheral-blood immune-cell subsets

  through study completion, an average of 1 year

• Quantity of DNA T-cell-receptor excision circles (TRECs) in peripheral-blood mononuclear cells

  through study completion, an average of 1 year

• Serum immunoglobulins levels

  through study completion, an average of 2 year

Study Arms (1)

Experimental Group

EXPERIMENTAL

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

Interventions

Lentiviral Vector Gene Therapy DEVICE

Lentiviral vector to transfer IL2RG complementary DNA to patients'bone marrow stem cells

Experimental Group

Eligibility Criteria

• Age: Up to 18 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• X-SCID patients diagnosed by IL2RG single gene mutation
• No HLA（human leukocyte antigen） matching donor
• Hematopoietic stem cell transplantation failed and the time from transplantation was more than 18 months
• Severe and persistent refractory infections
• Life expectancy of \> : 4 months
• HIV PCR in peripheral blood was negative
• the children and their families signed informed consent and were willing to enter the clinical trial and complete follow-up

You may not qualify if:

• The patient has diagnosed with hematological malignant diseases
• Received chemotherapy within 3 months
• HIV infection or HBV（hepatitis B virus） infection
• 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
• 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;
• Patients whose family members have no intention to continue the follow-up treatment in any link

Sponsors & Collaborators

• Children's Hospital of Chongqing Medical University: lead

Study Sites (1)

Children's Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400014, China

RECRUITING

Related Publications (3)

• 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.

  PMID: 30995372 BACKGROUND

• 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.

  PMID: 20660403 BACKGROUND

• 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.

  PMID: 27099176 BACKGROUND

MeSH Terms

Conditions

X-Linked Combined Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Severe Combined Immunodeficiency; Primary Immunodeficiency Diseases; Infant, Newborn, Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Xiaodong Zhao, PHD

  Assistant President of Children's Hospital of Chongqing Medical University

  STUDY DIRECTOR

Central Study Contacts

Xiaodong Zhao, PHD

CONTACT

18623070626; zhaoxd530@aliyun.com

Qiling Xu, MD

CONTACT

18581059910; 272864835@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident physician

Study Record Dates

• First Submitted: February 23, 2020
• First Posted: February 27, 2020
• Study Start: May 1, 2020
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2025
• Last Updated: March 27, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)