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X-Linked Combined Immunodeficiency DiseasesPhase 1/2LVXSCID-OCNCT03315078

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

A Phase 1/2 study testing CD34+ HSCs transduced with the lentivirus vector, VSV-G pseudotyped CL20-4i-EF1α-hγc-OPT, Palifermin and Busulfan in people with X-Linked Combined Immunodeficiency Diseases, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 2 to 40 years
What is being tested?
CD34+ HSCs transduced with the lentivirus vector, VSV-G pseudotyped CL20-4i-EF1α-hγc-OPT, Palifermin and Busulfan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
Apr 2012to Dec 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 40 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
Show all 37Show fewer
  • 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
  • b. Pulmonary function test (PFT) evidence for restrictive or obstructive disease that is 60% of Predicted for Age OR
  • c. Pulse oximetry 94% in room air (if patient is too young to comply with performance of pulmonary function tests [PFTs]).
  • iii. Gastrointestinal enteropathy:
  • a. Diarrhea-watery stools 3 times per day (of at least 3 months duration that is not a result of infection as defined in criterion number i. above) OR
  • b. Endoscopic evidence (gross and histologic) for enteropathy (endoscopy will only be performed if medically indicated) OR
  • c. 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 gastrostomy tube (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: 3rd 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

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site, 1 recruiting

  • Laboratory of Host Defenses (LHD), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)

    Bethesda, Maryland, 20892-1456

    Suk See DeRavin, M.D., Ph.D, 301-496-6772

    Recruiting

Other trials in United States

About this study

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.

Read the detailed description

This study will 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. XSCID is a severe genetic condition of the immune system.

Participants in this study will be treated at the National Institutes of Health (NIH) Clinical Center.

Before the gene transfer treatment, a participant's own CD34+ hematopoietic stem cells (HSCs) will have been or will be collected from the participant's blood or bone marrow. When the participant has the required number of HSCs harvested, then the participant's HSCs will be grown in tissue culture and exposed to the lentiviral gene transfer vector containing the corrective gene (VSV-G pseudotyped CL20-4i-EF1α-hγc-OPT). These gene corrected HSCs will be administered by intravenous (IV) infusion to the participant. To increase engraftment of the corrected HSCs, participants will receive a chemotherapy drug called busulfan on 2 days before the gene transfer treatment. Participants will also receive palifermin, which helps prevent mucositis, which is the main side effect from the busulfan.

After the gene transfer treatment, participants will be monitored to see if the treatment is safe and whether their immune system improves. Participants will be followed at frequent intervals for the first 2 years, and less frequently thereafter so that the effectiveness in restoration of immune function and the safety of the treatment can be evaluated. Additional safety follow-up may occur through Year 15.

Being tested
CD34+ HSCs transduced with the lentivirus vector, VSV-G pseudotyped CL20-4i-EF1α-hγc-OPT, Palifermin, Busulfan
Medical subject headings
X-Linked Combined Immunodeficiency Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CD34+ HSCs transduced with the lentivirus vector, VSV-G pseudotyped CL20-4i-EF1α-hγc-OPTBiological

    Administered by intravenous (IV) infusion

  • PaliferminDrug

    Administered by IV infusion at a dose of 60 mg/kg/day

  • BusulfanDrug

    Administered by IV infusion at a dose of approximately 3 mg/kg per day

Study groups in NCT03315078
Study groupRoleWhat they receive
Gene-Modified CD34+ HSCsExperimentalParticipants will receive palifermin on Days -6, -5, and -4 and then busulfan on Days -3 and -2. On Day 0, participants will undergo the gene transfer treatment with infusion of the gene-modified CD34+ HSCs. They will receive palifermin on Days 1, 2, and 3.
Receives: Biological: CD34+ HSCs transduced with the lentivirus vector, VSV-G pseudotyped CL20-4i-EF1α-hγc-OPT; Drug: Palifermin; Drug: Busulfan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Level of autologous transduced T-lymphocytes with functional γc

    Defined by their appearance and expansion in peripheral blood

    Measured: Measured through Year 2

  2. Incidence of serious side effects due to lentiviral gene transfer

    As determined by whether participants experience any grade 3 or greater toxicity that is directly attributed to the gene therapy procedure

    Measured: Measured through Year 15

  3. Distribution of integration sites of the lentiviral vector in reconstituted peripheral blood cells

    Based on statistical analysis

    Measured: Measured through Year 15

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2017
  2. Study startApr 2012
  3. Primary completionDec 2022 (estimated)
  4. Study completionDec 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03315078
Sponsor's protocol ID
11-I-0007
Acronym
LVXSCID-OC
Status last verified
Dec 2019
First submitted
16 Oct 2017
Last updated
4 Dec 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CD34+ HSCs transduced with the lentivirus vector, VSV-G pseudotyped CL20-4i-EF1α-hγc-OPT, Palifermin and Busulfan in people with X-Linked Combined Immunodeficiency Diseases, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 4 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Level of autologous transduced T-lymphocytes with functional γc (time frame: Measured through Year 2). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03315078.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2019.

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