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

NCT03315078 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 11-I-0007
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

X-Linked Combined Immunodeficiency Diseases

Outcome Measures

Primary Outcomes (3)

• Level of autologous transduced T-lymphocytes with functional γc

  Defined by their appearance and expansion in peripheral blood

  Measured through Year 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 through Year 15

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

  Based on statistical analysis

  Measured through Year 15

Study Arms (1)

Gene-Modified CD34+ HSCs

EXPERIMENTAL

Participants 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.

Biological: CD34+ HSCs transduced with the lentivirus vector, VSV-G pseudotyped CL20-4i-EF1α-hγc-OPT; Drug: Palifermin; Drug: Busulfan

Interventions

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

Administered by intravenous (IV) infusion

Gene-Modified CD34+ HSCs

Palifermin DRUG

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

Gene-Modified CD34+ HSCs

Busulfan DRUG

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

Gene-Modified CD34+ HSCs

Eligibility Criteria

• Age: 2 Years - 40 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

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)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

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

Bethesda, Maryland, 20892-1456, United States

RECRUITING

MeSH Terms

Conditions

X-Linked Combined Immunodeficiency Diseases

Interventions

Fibroblast Growth Factor 7; Busulfan

Condition Hierarchy (Ancestors)

Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Severe Combined Immunodeficiency; Primary Immunodeficiency Diseases; Infant, Newborn, Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Suk See DeRavin, M.D., Ph.D

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2017
• First Posted: October 19, 2017
• Study Start: April 1, 2012
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: December 4, 2019

Record last verified: 2019-12

Locations

US (1)