Gene Transfer for X-Linked Severe Combined Immunodeficiency in Newly Diagnosed Infants

NCT01512888 | Suspended Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: LVXSCID-NDP01HL053749
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

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 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.

Conditions

Severe Combined Immunodeficiency Disease, X-linked

Keywords

SCID; SCID-X1; X-linked SCID; immunodeficiency; gene therapy

Outcome Measures

Primary Outcomes (5)

• Number of patients with adequate cell collection and processing

  The number of patients who underwent no more than two bone marrow harvests and cryopreservation of at least 1.0 million cells/kg following vector transduction.

  Day 0

• Number of patients with adequate neutrophil count recovery after busulfan conditioning

  Adequate recovery is defined as absolute neutrophil count (ANC) \>500 cells/μl by day +42 unless the patient is neutropenic prior to busulfan administration.

  Day 42 post gene transfer

• Number of patients without Grade 4 adverse event (AE)

  The number of patients experiencing no directly related grade 4 or greater adverse event.

  42 days post gene transfer

• Number of patients with successful reconstitution

  Reconstitution with transduced cells defined as detection of vector-marked peripheral blood cells by real time PCR at or above 0.02% VCN in total WBC.

  42 days post gene transfer

• Number of patients with treatment failure

  Treatment failure will be defined as lack of adequate cell collection and processing, lack of neutrophil count recovery by day +42, occurrence of grade 4 or greater toxicities by day +42, and/or lack of detection of \>0.02% transduced cells in peripheral blood by day +42 post gene transfer.

  42 days post gene transfer

Other Outcomes (7)

• Pharmacokinetic (PK) variables of busulfan

  Days -2 and -1 prior to therapy

• Number of patients who achieve the desired therapeutic busulfan AUC

  Day 0

• B-cell function evaluated by Immune response

  52 weeks post gene transfer

Study Arms (1)

Treatment

EXPERIMENTAL

Participants will undergo a bone marrow harvest in the operating room to obtain bone marrow cells. Cells will be isolated and purified utilizing the CliniMacs device. These cells will undergo vector transduction with the lentiviral vector that contains a normal copy of the γc gene gene (CL20-i4-EF1α-hγc-OPT) and then the transduced cells will be reinfused back into the patient. Participants will receive a conditioning regimen of busulfan 3 days prior and 2 days prior to infusion of vector-corrected cells.intervention: CL20-i4-EF1α-hγc-OPT

Genetic: CL20-i4-EF1α-hγc-OPT; Drug: Busulfan; Device: CliniMacs

Interventions

CL20-i4-EF1α-hγc-OPT GENETIC

Participants will undergo infusion with autologous CD34+ bone marrow cells transduced with a lentiviral vector that contains a normal copy of the human γc gene.

Also known as: self inactivating lentiviral vector, IND 14570

Treatment

Busulfan DRUG

Given intravenously (IV).

Also known as: Busulfex®, Myleran®

Treatment

CliniMacs DEVICE

Isolation and purification of CD34+ stem cells will be done after the unmodified frozen backup is obtained and in accordance with our FDA IND and in accordance with the CliniMacs manual of operations.

Treatment

Eligibility Criteria

• Age: Up to 24 Months
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \* Treatment Eligibility Criteria:
• Age \<2 years at the time of enrollment.
• No prior therapy with allogeneic stem cell transplantation.
• A clinical diagnosis of SCID-X1 documented in the medical record.
• A proven mutation in the common gamma chain gene as defined by direct sequencing of patient DNA.
• Age \> 2 months to \< 1 year of age at the time of busulfan administration.
• Less than 300 CD3+ T-cells by flow cytometry or higher if evidence of maternal engraftment as supported by peripheral blood FISH analysis for XY and XX.
• Lymphocyte proliferation to phytohemagglutinin (PHA) \<10% of the lower limit of normal for the laboratory.

You may not qualify if:

• Availability of a HLA matched sibling for allogeneic transplantation
• Prior therapy with allogeneic stem cell transplantation
• Positive for HIV infection by genome PCR
• Presence of a medical condition indicating that survival will be less than 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
• A social situation indicating that the family may not be able to comply with protocol procedures and recommended medical care.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Assisi Foundation: collaborator
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (3)

University of California-San Francisco

San Francisco, California, 94158, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Seattle Children's Research Institute

Seattle, Washington, 98101, United States

Location

Related Publications (1)

• Mamcarz E, Zhou S, Lockey T, Abdelsamed H, Cross SJ, Kang G, Ma Z, Condori J, Dowdy J, Triplett B, Li C, Maron G, Aldave Becerra JC, Church JA, Dokmeci E, Love JT, da Matta Ain AC, van der Watt H, Tang X, Janssen W, Ryu BY, De Ravin SS, Weiss MJ, Youngblood B, Long-Boyle JR, Gottschalk S, Meagher MM, Malech HL, Puck JM, Cowan MJ, Sorrentino BP. Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1. N Engl J Med. 2019 Apr 18;380(16):1525-1534. doi: 10.1056/NEJMoa1815408.

  PMID: 30995372 DERIVED

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

X-Linked Combined Immunodeficiency Diseases; Immunologic Deficiency Syndromes

Interventions

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; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Stephen Gottschalk, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 13, 2012
• First Posted: January 19, 2012
• Study Start: August 17, 2016
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2034
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (3)