Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01306019
Recruitment Status : Recruiting
First Posted : March 1, 2011
Last Update Posted : October 10, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:


  • X-linked severe combined immunodeficiency (XSCID) is caused by a genetic abnormality in the IL2RG gene that affects the growth and development of immune cells such as white blood cells. Individuals with XSCID have difficulty fighting infections, which may lead to chronic or severe illness and death. The primary treatment for XSCID is replacement of the patient s immune system with a normal immune system through a bone marrow transplant. The best outcomes in transplant patients are achieved when the bone marrow comes from a sibling, but parents and matching unrelated donors can provide bone marrow for transplant as well. However, because these transplant procedures are not always effective, researchers are studying gene transfer treatment as an approach to treating XSCID.
  • Lentiviral gene transfer treatment uses good genes to replace defective genes. A lentivirus is a virus that has been modified to carry corrected genes into the blood through corrected stem cells. By collecting an individual s stem cells and modifying them with a lentivirus, the gene-corrected cells can be returned into the blood to help produce normal healthy immune cells. Gene transfer treatment with lentivirus vector has been used in humans but has never been studied in patients with XSCID.


- To determine the safety and effectiveness of lentiviral gene transfer as a treatment for children and adolescents with X-linked severe combined immunodeficiency.


- Children and adolescents between 2 and 20 years of age who have XSCID related to a defect in the IL2RG gene and who are not currently under treatment with strong immune-modulating or chemotherapy drugs.


  • Participants will be screened with a medical history, physical examination, blood and urine tests, and bone marrow samples to collect stem cells for the procedure.
  • Participants will be admitted to the National Institutes of Health Clinical Center 11 to 12 days before receiving gene-corrected blood stem cells.
  • Participants will receive palifermin for 3 days, followed by busulfan for 2 days. Palifermin will help prevent side effects from busulfan, and busulfan will help suppress the immune system in preparation for the gene transfer. Participants will have regular blood tests during this preparation period.
  • Participants will receive a transfer of their corrected blood stem cells about 36 to 48 hours after the second dose of busulfan. The cells will be injected over 5 to 10 minutes under close monitoring.
  • The day after the transfer, participants will have 3 more days of palifermin.
  • Participants will remain in the hospital for several weeks, possibly as long as 6 weeks, while the response to treatment is monitored.
  • Participants will continue to be monitored for immune function and possible side effects after leaving the hospital, and will be followed for up to 15 years after the procedure to evaluate the long-term effects of gene transfer therapy. The monitoring will involve regular physical exams and blood samples.

Condition or disease Intervention/treatment Phase
X-linked Severe Combined Immunodeficiency XSCID SCID-X1 Gamma C-Deficient SCID Other: Gene-modified CD34+ Hematopoietic stem cells Drug: Busulfan Phase 1 Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Lentiviral Gene Transfer for Treatment of Children Older Than 2 Years of Age With X-Linked Severe Combined Immunodeficiency
Study Start Date : February 26, 2011
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2025

Arm Intervention/treatment
Experimental: 1
Gene Therapy
Other: Gene-modified CD34+ Hematopoietic stem cells
Infusion of transduced autologous CD34+ Hematopoietic stem cells

Drug: Busulfan
Pre gene therapy conditioning regimen

Primary Outcome Measures :
  1. The primary objective is to assess the efficacy of immune reconstitution in XSCID patients transplanted with autologous CD34 plus cells that have been transduced with a self-inactivating lentiviral vector expressing a Gamma C gene. [ Time Frame: Primary endpoint evaluation at 2 years ]

Secondary Outcome Measures :
  1. To determine the incidence of serious side effects due to lentiviral gene transfer. [ Time Frame: Out to at least 5 years after treatment, though periodic follow-up will continue for 15 years as per FDA Guidance ]
  2. To determine the integration site distribution of the lentiviral vector in reconstituted peripheral blood cells. [ Time Frame: At intervals out to at least 5 years after treatment ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   2 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • A proven mutation in the common gamma chain gene as defined by direct sequencing of patient DNA
  • 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 greater than or equal to 10 kg
  • If previously transplanted, must be greater than or equal to 18 months post haploidentical HSCT
  • Expected survival of at least 120 days.
  • 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. If serum IgM<normal for age

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): greater than or equal to 3 significant new or chronic active infections during the 12 months preceding evaluation for enrollment.

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


-Hospitalization of any duration for infection


-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


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


-Pulse oximetry less than or equal to 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)


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


-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 greater than or equal to 10 lesions or there are two or more lesions at each of two or more widely separated anatomic sites; or there are greater than or equal to 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)


  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01306019

Layout table for location contacts
Contact: Nana Kwatemaa, R.N. (301) 451-7820
Contact: Suk S De Ravin, M.D. (301) 496-6772

Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Layout table for investigator information
Principal Investigator: Suk S De Ravin, M.D. National Institute of Allergy and Infectious Diseases (NIAID)

Additional Information:
Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT01306019     History of Changes
Other Study ID Numbers: 110007
First Posted: March 1, 2011    Key Record Dates
Last Update Posted: October 10, 2019
Last Verified: May 21, 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
X-Linked Severe Combined Immunodeficiency (XSCID)
Gene Transfer
Peripheral Blood Stem Cells
Common Gamma Chain (GC), Immune Reconstitution
Immune Reconstitution
X-Linked Severe Combined Immunodeficiency
Additional relevant MeSH terms:
Layout table for MeSH terms
Severe Combined Immunodeficiency
X-Linked Combined Immunodeficiency Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists