LVXSCID-ND: Gene Transfer for X-Linked Severe Combined Immunodeficiency (SCID) in Newly Diagnosed Infants

A Pilot Feasibility Study of Gene Transfer For X-Linked Severe Combined Immunodeficiency (SCID) in Newly Diagnosed Infants Using a Self-Inactivating Lentiviral Vector To Transduce Autologous CD34 + Hematopoietic Cells

Categories:

Hematological Disorders

Phase I/II

Diseases Treated:

X-linked Severe Combined Immunodeficiency (SCID-X1)

Eligibility Overview:

  • Diagnosis of Severe Combined Immunodeficiency Disease, X-linked (SCID-X1)
  • Newborn to 12 months of age
  • No prior therapy with allogeneic stem cell transplantation
  • No HIV infection
  1. Brief Summary

    Severe combined immunodeficiency disease, X-linked (SCID-X1) is a genetic disorder of blood cells caused by DNA changes in a gene that is required for the normal development of the human immune system.

    The purpose of this study is to determine if a new method, called lentiviral gene transfer, can be used to treat SCID-X1. This method involves transferring a normal copy of the common gamma chain (γc) gene into the participant’s bone marrow stem cells.

    The investigators want to determine if the procedure is safe, whether it can be done according to the methods they have developed, and whether the procedure will provide a normal immune system for the patient. It is hoped that this type of gene transfer may offer a new way to treat children with SCID-X1 that do not have a brother or sister who can be used as a donor for stem cell transplantation.

    Primary Objectives

    The main goals of this phase 1/phase 2 study are to:

    • Evaluate the safety and feasibility of obtaining and infusing at least 3 million CD34+ cells per kilogram of body weight in SCID-X1 infants
    • Assess the safety of the study procedure and assess for early evidence of significant T-cell reconstitution at 16 (±1) weeks
    • Evaluate the efficacy of lentiviral gene transfer for inducing significant T-cell reconstitution 52 weeks (+2 weeks) after transplantation

    Interventions

    • Genetic: CL20-4i-EF/a-hγc-OPT
    • Drug: busulfan

    Study Arm

    Experimental: Treatment

    Participants will undergo a bone marrow harvest in the operating room to obtain bone marrow cells. These cells will undergo vector transduction with the lentiviral vector that contains a normal copy of the γc gene gene (CL20-4i-EF/a-hyc-OPT). These transduced cells will be cryopreserved. The patient will receive targeted busulfan conditioning over 2 days and then the thawed, transduced cells will be reinfused back into the patient. 

    Eligibility Criteria

    Inclusion Criteria:

    • Diagnosis of SCID-X1
    • Proven mutation in the γc gene
    • Age newborn to <1 year of age
    • Less than 300 circulating CD3+ T-cells/ul by flow cytometry or higher if evidence of maternal engraftment

    Exclusion Criteria:

    • Availability of an HLA matched sibling for allogeneic transplantation
    • Prior therapy with allogeneic stem cell transplantation
    • Positive for HIV infection
    • Presence of a medical condition indicating that survival will be <16 weeks such as the requirement for mechanical ventilation, severe failure of a major organ system, or evidence of a serious, progressive infection that is refractory to medical therapy
    • The presence of any medical contraindications to general anesthesia and bone marrow harvest by aspiration

    Study Design

    • Endpoint Classification: Safety/Efficacy Study
    • Intervention Model: Single Group Assignment
    • Masking: Open Label
    • Primary Purpose: Treatment
  2. About this clinical trial

    Severe Combined Immunodeficiency Disease, X-linked (SCID-X1) is a rare, genetic (inherited) disorder of blood cells caused by DNA changes in a gene that is required for the normal development of a child’s immune system. SCID-X1 almost always occurs in boys and affects approximately one in 50,000 to 100,000 newborns.

    Some children with SCID-X1 have been successfully treated with stem cell transplantation. Stem cells are cells that have the potential to develop into different cells in the body. The best type of donor for a stem cell transplant is a brother or sister who is a “match” for the patient’s immune type.

    Cure rates are much lower for children who do not have a brother or sister that is a close match. For this reason, St. Jude is offering this clinical trial to find better treatments for children with SCID-X1.

    Purpose of this clinical trial

    This research study is looking at treating SCID-X1 with a new method for gene transfer. Gene transfer is a process by which a corrected (normal) copy of an abnormal gene is transferred into stem cells.

    The main purpose of LVXSCID-ND is to find out if a new gene transfer method, called lentiviral gene transfer, can be used to treat children with SCID-X1. This method involves transferring a normal copy of the common gamma chain gene into your child’s bone marrow stem cells.

    St Jude researchers want to see if lentiviral gene transfer is safe, whether it can be done according to the methods developed at St. Jude, and whether the gene transfer will provide a normal immune system for your child.

    Treatment

    There are three parts to this study:

    1. Screening – Tests and procedures will be done to find out if this study is a good option for your child.
    2. Treatment
      • Bone marrow cells will be collected from your child in an operating room and the corrected common gamma gene will be inserted into your child’s bone marrow cells (gene transfer).
      • Your child will then be treated with a chemotherapy conditioning regimen to remove the remaining bone marrow cells and create space for the corrected (gene transferred) cells.
      • The corrected cells will be given back to your child through an infusion (through a vein).
      • Your child will stay in the hospital until his immune system recovers and the doctors believe he is well enough to go home.
    3. Follow-up – After treatment ends, your child will have routine follow-up examinations and medical tests. St. Jude researchers will continue to collect medical information about how your child is doing.

    Eligibility overview

    • Diagnosis of Severe Combined Immunodeficiency Disease, X-linked (SCID-X1)
    • Newborn to 12 months of age
    • No prior therapy with allogeneic stem cell transplantation
    • No HIV infection
  3. LVXSCID-ND Quick View

    Sponsor

    St. Jude Children’s Research Hospital

    Collaborators National Heart, Lung, and Blood Institute and the Assisi Foundation

    ClinicalTrials.gov identifier

    NCT0151288

    Trial start date

    February 2012

    Estimated enrollment

    28

    Study type

    Interventional

    Study phases

    Phase 1
    Phase 2

    Conditions

    • Severe Combined Immunodeficiency Disease
    • X-linked (SCID-X1)

    Ages

    Newborn to <1 year

    Principal investigator

    Brian Sorrentino, MD

    Study sites

    St. Jude Children’s Research Hospital and collaborating sites in the U.S.

    For a consultation or to discuss LVXSCID-ND

    Brian Sorrentino, MD
    901-575-2727
    brian.sorrentino@stjude.org

Contact

Brian Sorrentino, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105 USA
Phone: 901-595-2727
Email: brian.sorrentino@stjude.org

Referring or consulting clinicians only: protocolinfo@stjude.org
For all other inquiries about St. Jude Children's Research Hospital studies: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.