Lentiviral Gene Transfer for Treatment of Children Older Than 2 Years of Age With X-Linked Severe Combined Immunodeficiency

Status unconfirmed · Phase 1/Phase 2

Conditions studied: X-Linked Combined Immunodeficiency Diseases

In brief

The purpose of this study is to evaluate the safety and effectiveness of lentiviral gene transfer treatment at restoring immune function to participants with X-linked severe combined immunodeficiency (XSCID) who are 2 to 40 years of age, and have significant impairment of immunity.

Key facts

Study ID

NCT03315078

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

13

Starts

2012-04-01

Expected to finish

2022-12-01

Last updated by the study team

2019-12-04

Who can join

Age: 2 and older, up to 40. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• A proven mutation in the common gamma chain gene as defined by direct sequencing of patient DNA
• Human leukocyte antigen (HLA) typing of the patient will have been performed before enrollment
• No available HLA matched sibling donor as determined before enrollment.
• Must be between 2 and 40 years of age and weigh 10 kg
• If previously transplanted, must be 18 months post-hematopoietic stem cell transplant (HSCT)
• Expected survival of at least 120 days.
• Documented to be negative for HIV infection by genome polymerase chain reaction (PCR)
• The patient must be judged by the primary evaluating physician to have a suitable family and social situation consistent with ability to comply with protocol procedures and the long-term follow-up requirements.
• Medical lab data (historical) of severe B cell dysfunction (low or absent immunoglobulin G [IgG] levels, failed immune response to vaccines); OR demonstrated requirement for intravenous gamma globulin (IVIG) (significant drop over 3 to 6 weeks between peak and trough IgG levels).
• Must be willing to have blood and tissue samples stored. IN ADDITION, patients must satisfy the following Laboratory Criteria AND Clinical Criteria:
• Laboratory Criteria: (at least 1 must be present)
• CD4+ lymphocytes: absolute number less than or equal to 50% of the lower limit of normal (LLN)
• CD4+CD45RA+ lymphocytes: absolute number less than or equal to 50% of the LLN OR T-cell receptor excision circles (TRECs) less than or equal to 5% of normal for age.
• Memory B Cells: absolute number less than or equal to 50% of LLN
• Serum immunoglobulin M (IgM) less than normal for age
• Natural killer (NK) cells: absolute number less than or equal to 50% of LLN
• Lymphocyte proliferative response to each of 2 mitogens, phytohemagglutinin (PHA) and concanavalin A (ConA), is less than or equal to 25% compared with a normal control.
• Molecular spectratype analysis- absent or very oligoclonal (1-3 dominant peaks) in greater than or equal to 6 of the 24 Vbeta T-cell receptor families.
• Clinical Criteria: (at least 1 must be present)
• i. Infections (not including molluscum, warts or mucocutaneous candidiasis; see vii and viii below): 3 significant new or chronic active infections during the 2 years preceding evaluation for enrollment, with each infection accounting for one criteria. Infections are defined as an objective sign of infection (fever greater than 38.3\^0C [101\^0F] or neutrophilia or pain/redness/swelling or radiologic/ultrasound imaging evidence or typical lesion or histology or new severe diarrhea or cough with sputum production). In addition to one or more of these signs/symptoms of possible infection, there also must be at least 1 of the following criteria as evidence of the attending physician's "intent to treat" a significant infection (a. and b.) or objective evidence for a specific pathogen causing the infection (c.)
• a. Treatment (not prophylaxis) with systemic antibacterial, antifungal or antiviral antibiotics 14 days OR
• b. Hospitalization of any duration for infection OR
• c. Isolation of a bacteria, fungus, or virus from biopsy, skin lesion, blood, nasal washing, bronchoscopy, cerebrospinal fluid or stool likely to be an etiologic agent of infection
• ii. Chronic pulmonary disease as defined by:
• a. Bronchiectasis by x-ray computerized tomography OR

You may not qualify if…

• Any current or pre-existing hematologic malignancy
• Current treatment with any chemotherapeutic agent (becomes eligible if not on treatment for at least 3 months)
• Documented HIV-1 infection
• Documented active Hepatitis B infection
• Childhood malignancy (occurring before 18 years of age) in the patient or a first degree relative, or previously diagnosed known genotype of the subject conferring a predisposition to cancer (no DNA or other testing for cancer predisposition genes will be performed as part of the screen for this protocol)

Where it is running

• Laboratory of Host Defenses (LHD), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) — Bethesda, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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