Gene Therapy for X Linked Severe Combined Immunodeficiency

• Sponsor: Children's Hospital of Chongqing Medical University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04286815
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 60
• Patients Per Site Per Month: 0.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Gene Therapy	Device: Lentiviral Vector Gene Therapy	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Gene Therapy for X Linked Severe Combined Immunodeficiency
• Anticipated Study Start Date: May 1, 2020
• Anticipated Primary Completion Date: May 1, 2023
• Anticipated Study Completion Date: May 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 1-year survival rate 1-year survival rate [one year after gene therapy of last recruited patient]

   1-year survival rate of 10 recruited patients

2. 3-year survival rate [three years after gene therapy of last recruited patient]

   3-year survival rate of 10 recruited patients

3. 5-year survival rate [five years after gene therapy of last recruited patient]

   5-year survival rate of 10 recruited patients

Secondary Outcome Measures

1. Growth velocity after gene therapy,weight in kilograms, height in meters [through study completion, an average of 2 year]

   Body weight and height of patients will be assessed prior to (month 0) and post gene therapy,weight in kilograms, height in meters

2. Vector marking (vector copy number per cell) in blood and bone marrow cells [through study completion, an average of 1 year]

   vector marking in T cells, B cells, NK cells, myeloid cells, and bone marrow progenitors.

3. Absolute numbers of peripheral-blood immune-cell subsets [through study completion, an average of 1 year]

   Absolute numbers of peripheral-blood immune-cell subsets，as determined by means of standard flow cytometry

4. Quantity of DNA T-cell-receptor excision circles (TRECs) in peripheral-blood mononuclear cells [through study completion, an average of 1 year]

   Quantity of DNA T-cell-receptor excision circles (TRECs) in peripheral-blood ，as determined by means of quantitative polymerase chain reaction (PCR)

5. Serum immunoglobulins levels [through study completion, an average of 2 year]

   Serum immunoglobulins levels will be reported IgM（immunoglobulin M） in mg/dL Serum immunoglobulins levels will be reported IgM in mg/dL

6. Number of patients without intravenous immune globulin supplementation [through study completion, an average of 2 year]

   Number of patients without intravenous immune globulin supplementation after gene therapy

7. Number of patients who has a response to vaccines [through study completion, an average of 2 year]

   Number of patients who has a response to vaccines after gene therapy

8. Number of patients who recovers from previous infection（virus and bacteria） [through study completion, an average of 2 year]

   Number of patients who recovers from previous infection（virus and bacteria）after gene therapy

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Chongqing Medical University	Chongqing	Chongqing	China	400014

Sponsors and Collaborators

• Children's Hospital of Chongqing Medical University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.

• Responsible Party: mingfeng hu, Resident physician, Children's Hospital of Chongqing Medical University
• ClinicalTrials.gov Identifier: NCT04286815
• Other Study ID Numbers: CHCMU gene therapy
• First Posted: Feb 27, 2020
• Last Update Posted: Mar 27, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by mingfeng hu, Resident physician, Children's Hospital of Chongqing Medical University: Gene Therapy; X Linked Severe Combined Immunodeficiency; Lentiviral Vector
• Additional relevant MeSH terms: Severe Combined Immunodeficiency; X-Linked Combined Immunodeficiency Diseases; Immunologic Deficiency Syndromes

Study Results

No Results Posted as of Mar 27, 2020