Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)

• Register: ClinicalTrials.gov
• Last refreshed on: 29 April 2024
• Main ID: NCT01306019
• Date of registration: 26/02/2011
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)
• Scientific title: Lentiviral Gene Transfer for Treatment of Children Older Than 2 Years of Age With X-Linked Severe Combined Immunodeficiency
• Date of first enrolment: September 25, 2012
• Target sample size: 40
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT01306019
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

• Name: Suk S De Ravin, M.D.

• Name: Suk S De Ravin, M.D.
• Affiliation: National Institute of Allergy and Infectious Diseases (NIAID)

Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

- A proven mutation in the common gamma chain gene as defined by direct sequencing of
patient DNA

- No available HLA matched sibling donor as determined before enrollment. (HLA typing
will be performed prior to enrollment)

- Must be between 2 and 40 years of age and weigh greater than or equal to 10 kg

- If previously transplanted, must be greater than or equal to 18 months post HSCT

- Expected survival of at least 120 days.

- Participants of reproductive potential must agree to consistently use highly effective
contraception throughout study participation and for at least 2 years post-treatment.
Acceptable forms of contraception are:

--For males: Condoms or other contraception with partner.

- Documented to be negative for HIV infection by genome 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 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: (greater than or equal to 1 must be present)

i. CD4+ lymphocytes: absolute number less than or equal to 50 percent of the lower limit of
normal (LLN)

ii. CD4 plus CD45RA+ lymphocytes: absolute number less than or equal to 50 percent of the
LLN OR T-cell receptor excision circles (TRECs)squared less than or equal to 5 percent of
normal for age.

iii. Memory B Cells: absolute numberless than or equal to 50percent of LLN

iv. Serum IgM
v. NK cells: absolute number less than or equal to 50 percent of LLN

vi. Lymphocyte proliferative response to each of 2 mitogens, phytohemagglutinin (PHA) and
concanavalin A (ConA), is squared 25 percent with a normal control.

vii. Molecular spectratype analysis- absent or very oligoclonal (1-3 dominant peaks) in
greater than or equal to 6 of the 24 V- Beta T-cell receptor families.

Clinical Criteria: (greater than or equal to 1 must be present):

i Infections (not including molluscum, warts or mucocutaneous candidiasis; see vii and viii
below):

Three 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 degrees C
[101 degrees F] 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.)

-Treatment (not prophylaxis) with systemic antibacterial, antifungal or antiviral
antibiotics greater than or equal to 14 days

OR

-Hospitalization of any duration for infection

OR

-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:

-Bronchiectasis by x-ray computerized tomography

OR

-Pulmonary function test (PFT) evidence for restrictive or obstructive disease that is 60
percent of Predicted for Age

OR

-Pulse oximetry 94 percent in room air (if patient is too young to comply with performance
of PFTs).

iii Gastrointestinal enteropathy:

-Diarrhea-watery stools greater than or equal to 3 times per day (of at least 3 months
duration that is not a result of infection as defined in criterion above)

OR

-Endoscopic evidence (gross and histologic) for enteropathy (endoscopy will only be
performed if medically indicated)

OR

-Other evidence of enteropathy or bacterial overgrowth syndrome: including malabsorption of
fat soluble vitamin(s), abnormal D-xylose absorption, abnormal hydrogen breath test,
evidence of protein losing enteropathy (for example increasingly high or frequent dosing of
intravenous gamma globulin supplement required to maintain blood IgG level).

iv Poor nutrition: Requires G-tube or intravenous feeding supplement to maintain weight or
nutrition.

v Auto- or allo-immunity: Examples must include objective physical findings that include,
but are not limited to any one of alopecia, severe rashes, uveitis, joint pain with redness
or swelling or limitation of movement that is not a result of infection, lupus-like
lesions, and granulomas (Does not include auto- or allo-immune enteropathy which is
criterion iii). Where possible and appropriate, diagnosis will be supported by
histopathology or other diagnostic modality.

vi Failure to grow in height: less than or equal to 3 rd percentile for age

vii Skin molluscum contagiosum OR warts (this criterion is satisfied if molluscum consists
of 10 lesions or there are two or more lesions at each of two or more widely separated
anatomic sites; or there are 3 warts at different anatomic sites at the same time; or the
patient has both molluscum and warts)

viii Mucocutaneous candidiasis (chronic oral thrush or candida esophagitis or candida
intertriginous infection or candida nail infections; must be culture positive to satisfy
this criterion)

ix Hypogammaglobulinemia: requires regular IgG supplementation

INCLUSION OF VULNERABLE PARTICIPANTS:

- Children: Children 2 years of age and older may enroll on this study because the
condition under study affects children and the study holds the prospect for direct
benefit.

- Adults who lack capacity to consent to research participation: Adults who are unable
to consent are eligible for enrollment in this protocol because patients with SCID-X1
may have serious complications affecting decision-making ability and because the study
intervention might provide direct benefit. Similarly, enrolled participants who lose
the ability to provide ongoing consent (either

temporarily or permanently) during study participation may continue in the study following
NIH


Age minimum: 2 Years
Age maximum: 40 Years
Gender: Male

Health Condition(s) or Problem(s) studied

X-linked Severe Combined Immunodeficiency (XSCID)

Intervention(s)

Drug: Busulfan

Drug: Palifermin

Biological: Ex vivo culture and transduction of the patient's autologous CD34+ HSC with lentivirus vector VSV-G pseudotyped CL20- 4i-EF1alpha-hgammac-OPT vector

Primary Outcome(s)

Early evidence for efficacy will be defined by appearance and expansion in the circulation of autologous transduced T-lymphocytes with functional gmama-c and improved laboratory measures of immune function in the interim evaluation of these para... [Time Frame: 1 year]

Secondary Outcome(s)

evidence for efficacy at 2 years after treatment will include these same laboratory parameters measured at the 2 year time point plus evidence for clinical benefit [Time Frame: 2 years]

Secondary ID(s)

110007

11-I-0007

Source(s) of Monetary Support

Please refer to primary and secondary sponsors