A clinical trial to study the effects of genetically modified patients' CD34+ cells in patients with X-linked Severe Combined Immunodeficiency

Phase 1

• Conditions: Severe combined immunodeficiency disorder (SCID) is a heterogeneous group of inherited disorders characterized by a profound reduction or absence of T lymphocyte function, resulting in lack of both cellular and humoral immunity. The most common form of SCID is an X-linked form (SCID-X1), which accounts for 30-50% of all cases. Children with SCID lack virtually all immune protection from pathogens. They are prone to repeated and persistent infections that can be very serious or life threatening.; MedDRA version: 20.0 Level: LLT Classification code 10069566 Term: Severe combined immunodeficiency syndrome System Organ Class: 100000004850; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2018-000673-68-GB
• Lead Sponsor: Great Ormond Street Hospital for Children NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-07-27
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 5

Inclusion Criteria

All subjects must fulfill the following criteria to be included in the study:
1.Diagnosis of SCID-X1 based on immunophenotype and lack of T cell function (proliferation to PHA <10% of the lower limit of normal for the laboratory) AND confirmed by a mutation in IL2RG
2.Lack of an HLA identical (A, B, C, DR, DQ) related donor
3.Age <5 years
4.Signed informed consent
5.Documentation of willingness to follow up for 15 years post-infusion
6.If the patient has previously undergone allogeneic transplant, lack of donor T cell engraftment must be documented.
7.Age at least 8 weeks of age by the time of busulfan administration

Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

Subjects will not be eligible for the study if any of the following criteria is fulfilled:
1.Patients with an active, therapy-resistant infection. Infections that are known to be highly morbid in SCID patients will be considered active and therapy-resistant if the infectious agent is repeatedly isolated despite a minimum of 2 weeks of appropriate therapy and is associated with significant organ dysfunction (including but not limited to abnormalities listed below).
a.Mechanical ventilation including continuous positive airway pressure
b.Abnormal liver function defined by AST and ALT >10 times the upper range of normal OR Bilirubin >2 mg/dL
c.Shortening fraction on echocardiogram <25% or ejection fraction <50%
d.Renal failure defined as glomerular filtration rate <30 ml/min/1.73 m2 or dialysis dependence
2.Uncontrolled seizure disorder
3.Encephalopathy
4.Documented coexistence of any disorder known to affect DNA repair
5.Diagnosis of active malignant disease other than EBV-associated lymphoproliferative disease
6.Patients with evidence of infection with HIV-1
7.Previous allogeneic transplant with cytoreductive chemotherapy
8.Major (life-threatening) congenital anomalies. Examples of major (life-threatening) congenital anomalies” include, but are not limited to: unrepaired cyanotic heart disease, hypoplastic lungs, anencephaly or other major central nervous system malformations, other severe non-repairable malformations of the gastrointestinal or genitourinary tracts that significantly impair organ function.
9.Other conditions which in the opinion of the P.I. or Co-investigators, contra-indicate collection and/or infusion of transduced cells or indicate patient’s inability to follow the protocol. These may include for example clinical ineligibility to receive anaesthesia, severe deterioration of clinical condition of the patient after collection of bone marrow but before infusion of transduced cells, or documented refusal or inability of the family to return for scheduled visits. There may be other unforeseen rare circumstances that would result in exclusion of the patient, such as sudden loss of legal guardianship.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified