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Gene Therapy for X Linked Severe Combined Immunodeficiency

Primary Purpose

Gene Therapy

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Lentiviral Vector Gene Therapy
Sponsored by
Children's Hospital of Chongqing Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gene Therapy focused on measuring Gene Therapy, X Linked Severe Combined Immunodeficiency, Lentiviral Vector

Eligibility Criteria

undefined - 18 Years (Child, Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital of Chongqing Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental Group

Arm Description

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）.

Outcomes

Primary Outcome Measures

1-year survival rate 1-year survival rate
1-year survival rate of 10 recruited patients
3-year survival rate
3-year survival rate of 10 recruited patients
5-year survival rate
5-year survival rate of 10 recruited patients

Secondary Outcome Measures

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
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.
Absolute numbers of peripheral-blood immune-cell subsets
Absolute numbers of peripheral-blood immune-cell subsets，as determined by means of standard flow cytometry
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)
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
Number of patients without intravenous immune globulin supplementation
Number of patients without intravenous immune globulin supplementation after gene therapy
Number of patients who has a response to vaccines
Number of patients who has a response to vaccines after gene therapy
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

Full Information

First Posted
February 23, 2020
Last Updated
March 26, 2020
Sponsor
Children's Hospital of Chongqing Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT04286815
Brief Title
Gene Therapy for X Linked Severe Combined Immunodeficiency
Official Title
Gene Therapy for X Linked Severe Combined Immunodeficiency
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2020 (Anticipated)
Primary Completion Date
May 1, 2023 (Anticipated)
Study Completion Date
May 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Hospital of Chongqing Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gene Therapy
Keywords
Gene Therapy, X Linked Severe Combined Immunodeficiency, Lentiviral Vector

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental Group
Arm Type
Experimental
Arm Description
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）.
Intervention Type
Device
Intervention Name(s)
Lentiviral Vector Gene Therapy
Intervention Description
Lentiviral vector to transfer IL2RG complementary DNA to patients'bone marrow stem cells
Primary Outcome Measure Information:
Title
1-year survival rate 1-year survival rate
Description
1-year survival rate of 10 recruited patients
Time Frame
one year after gene therapy of last recruited patient
Title
3-year survival rate
Description
3-year survival rate of 10 recruited patients
Time Frame
three years after gene therapy of last recruited patient
Title
5-year survival rate
Description
5-year survival rate of 10 recruited patients
Time Frame
five years after gene therapy of last recruited patient
Secondary Outcome Measure Information:
Title
Growth velocity after gene therapy,weight in kilograms, height in meters
Description
Body weight and height of patients will be assessed prior to (month 0) and post gene therapy,weight in kilograms, height in meters
Time Frame
through study completion, an average of 2 year
Title
Vector marking (vector copy number per cell) in blood and bone marrow cells
Description
vector marking in T cells, B cells, NK cells, myeloid cells, and bone marrow progenitors.
Time Frame
through study completion, an average of 1 year
Title
Absolute numbers of peripheral-blood immune-cell subsets
Description
Absolute numbers of peripheral-blood immune-cell subsets，as determined by means of standard flow cytometry
Time Frame
through study completion, an average of 1 year
Title
Quantity of DNA T-cell-receptor excision circles (TRECs) in peripheral-blood mononuclear cells
Description
Quantity of DNA T-cell-receptor excision circles (TRECs) in peripheral-blood ，as determined by means of quantitative polymerase chain reaction (PCR)
Time Frame
through study completion, an average of 1 year
Title
Serum immunoglobulins levels
Description
Serum immunoglobulins levels will be reported IgM（immunoglobulin M） in mg/dL Serum immunoglobulins levels will be reported IgM in mg/dL
Time Frame
through study completion, an average of 2 year
Title
Number of patients without intravenous immune globulin supplementation
Description
Number of patients without intravenous immune globulin supplementation after gene therapy
Time Frame
through study completion, an average of 2 year
Title
Number of patients who has a response to vaccines
Description
Number of patients who has a response to vaccines after gene therapy
Time Frame
through study completion, an average of 2 year
Title
Number of patients who recovers from previous infection（virus and bacteria）
Description
Number of patients who recovers from previous infection（virus and bacteria）after gene therapy
Time Frame
through study completion, an average of 2 year

10. Eligibility

Sex
Male
Gender Based
Yes
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaodong Zhao, PHD
Phone
18623070626
Email
zhaoxd530@aliyun.com
First Name & Middle Initial & Last Name or Official Title & Degree
Qiling Xu, MD
Phone
18581059910
Email
272864835@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaodong Zhao, PHD
Organizational Affiliation
Assistant President of Children's Hospital of Chongqing Medical University
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital of Chongqing Medical University
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400014
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaodong Zhao, PhD
Phone
18623070626
Email
zhaoxd530@aliyun.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30995372
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.
Results Reference
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PubMed Identifier
20660403
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.
Results Reference
background
PubMed Identifier
27099176
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. Erratum In: Sci Transl Med. 2016 Jun 1;8(341):341er5.
Results Reference
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Gene Therapy for X Linked Severe Combined Immunodeficiency

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