LVXSCID-ND: Gene Therapy for X-Linked Severe Combined Immunodeficiency (SCID-X1) in Newly Diagnosed Infants

A Pilot Feasibility Study of Gene Transfer For X-Linked Severe Combined Immunodeficiency (SCID-X1) in Newly Diagnosed Infants Using a Self-Inactivating Lentiviral Vector To Transduce Autologous CD34 + Hematopoietic Stem Cells

Categories:

Hematological Disorders

Phase I/II

Immunodeficiency Diseases

Diseases Treated:

X-linked Severe Combined Immunodeficiency (SCID-X1)

Eligibility Overview:

  • Diagnosis of Severe Combined Immunodeficiency, X-linked (SCID-X1)
  • Newborn to 2 years of age
  • No prior therapy with allogeneic stem cell transplantation
  • No HIV infection
  1. Brief Summary

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

    The purpose of this study is to determine if a new method of gene therapy, 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 bone marrow transplantation.

    Primary Objectives

    • Evaluate the safety and feasibility of obtaining and infusing at least 1 million CD34+ cells per kilogram of body weight in SCID-X1 infants
    • Evaluate the safety of administering subablative busulfan conditioning and the transduced cell product, and in particular, the incidence of hematopoietic recovery in the first 42 days.
    • Evaluate the efficacy of lentiviral gene transfer for inducing significant T-cell reconstitution 52 weeks (+2 weeks) after transplantation

    Interventions

    • Stem cell infusion: autologous CD34+ hematopoietic stem cells, genetically modified with a lentiviral vector encoding the γc gene
    • Drug: busulfan

    Study Arm

    Experimental: Treatment

    Participants will undergo a bone marrow harvest in the operating room to obtain bone marrow stem cells. These stem cells will undergo a process called “vector transduction” during which the lentiviral vector carries a normal copy of the gene into patient’s stem cells. These cells treated with the vector (transduced cells)  will then be cryopreserved. The patient will receive low dose of chemotherapy (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 2 years 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

    Some children with SCID-X1 have been successfully treated with bone marrow transplantation if they have a matched brother or sister donor.

    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.

    In this study, children with SCID-X1 will be treated with gene therapy. Researchers will transfer a normal (corrected) copy of the child’s abnormal gene into the child’s bone marrow cells. This procedure is called gene transfer.

    Purpose of this clinical trial

    The main purpose of LVXSCID-ND is to find out if a new gene therapy, called lentiviral gene transfer, can be used to treat children with SCID-X1. St Jude researchers want to learn if this therapy 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 gene will be inserted into your child’s bone marrow cells (gene transfer).
      • Your child will then be treated with a low chemotherapy medicine 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, X-linked (SCID-X1)
    • Newborn to 2 years 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 University of California, San Francisco; Seattle Children's Hospital

    ClinicalTrials.gov identifier

    NCT01512888

    Trial start date

    February 2012

    Estimated enrollment

    28

    Study type

    Interventional

    Study phases

    Phase 1
    Phase 2

    Conditions

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

    Ages

    Newborn to 2 years

    Principal investigator

    Stephen Gottschalk, MD

    Study sites

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

    For a consultation or to discuss LVXSCID-ND

    St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: 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.