Recruiting
Phase 1
Phase 2

Autologous Gene Therapy

Sponsor:

UCLA

Code:

NCT03538899

Conditions

Severe Combined Immunodeficiency

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

AProArt-CD34

CliniMACS® CD34 Reagent System cell sorter device

Busulfan

Study Details

Brief summary:

This study aims to determine if a new method can be used to treat Artemis-deficient Severe Combined Immunodeficiency (ART-SCID), a severe form of primary immunodeficiency caused by mutations in the DCLRE1C gene. This method involves transferring a normal copy of the DCLRE1C gene into stem cells of an affected patient. Participants will receive an infusion of stem cells transduced with a self-inactivating lentiviral vector that contains a normal copy of the DCLRE1C gene. Prior to the infusion they will receive sub-ablative, dose-targeted busulfan conditioning. The study will investigate if the procedure is safe, whether it can be done according to the methods described in the protocol, and whether the procedure will provide a normal immune system for the patient. A total of 24 newly diagnosed patients will be enrolled at the University of California San Francisco in this single-site trial and will be followed for 15 years post-infusion. It is hoped that this type of gene transfer may offer improved outcomes for ART-SCID patients who lack a brother or sister who can be used as a donor for stem cell transplantation or who have failed to develop a functioning immune system after a previous stem cell transplant.

Conditions

Severe Combined Immunodeficiency

Study ID

NCT03538899

Start date

May 31, 2018

Status verified date

Feb, 2026

Completion date

Jun, 2038

Anticipated

Primary completion date

Jun, 2038

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • ≥2.0 months of age at initiation of busulfan conditioning
  • New diagnosis of typical or minimally leaky ART-SCID, as defined by the criteria below:
  • Artemis deficiency with bi-allelic pathogenic or likely pathogenic mutations in DCLRE1C; AND
  • CD3 count < 50 autologous cells/µL (typical ART-SCID) OR spontaneous maternal chimerism, OR CD3 count >50/µL and <300/uL and with restricted T cell receptor Vb diversity; AND
  • CD45 cell response to mitogens (PHA) < 50% of the lower limit of normal range for the lab (leaky ART-SCID).
  • No medically eligible HLA-identical sibling with a normal immune system who could serve as an allogeneic bone marrow donor (applies to newly diagnosed patients only).

Exclusion Criteria:

  • Presence of a medically eligible HLA-matched sibling
  • Evidence of HIV infection by polymerase chain reaction or p24 antigen testing.
  • Unable to tolerate general anesthesia and/or marrow harvest or insertion of central venous catheter.
  • Any one of liver function tests AST, ALT, gamma-glutamyl transpeptidase (GGT) >5X the upper limit of normal for lab and/or total bilirubin >2.0 mg/dl (not due to Gilbert's) at the time of planned initiation of busulfan conditioning unless the elevated LFTs are considered to be due to medication, a viral infection for which there is no treatment other than reconstituting T cell immunity, or maternal GVHD.
  • Presence of any severe medical conditions making a patient unsuitable for busulfan administration
  • Presence of a recognized second gene mutation that results in an autosomal dominant or recessive disorder intrinsic to hematopoietic cells and that could be treated by an allogeneic HCT.
  • Presence of a medical condition indicating that survival is predicted to be less than 4 months, 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.
  • A social situation indicating that the family may not be able to comply with protocol procedures and recommended medical care and follow-up.
  • Other conditions which in the opinion of the Principal Investigator and/or co-investigators, contra-indicate the infusion of transduced cells or study participation.

Study Design

Enrollment

24 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Gene therapy (AProArt)

Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency (ART-SCID) Using a Self-Inactivating Lentiviral Vector (AProArt) to Transduce Autologous CD34 Hematopoietic Cells. The CliniMACS® CD34 Reagent System sorter device will be used to select CD34 cells. Patients will be conditioned with low dose busulfan prior to transplant.

Interventions

AProArt-CD34

Participants will undergo infusion with autologous hematopoietic cells transduced with a lentiviral vector, AProArt, which contains the correct form of DCLRE1C complementary deoxyribonucleic acid DNA, after receiving sub-ablative, exposure-targeted busulfan conditioning.

CliniMACS® CD34 Reagent System cell sorter device

Processing of hematopoietic progenitor cells to select CD34 cells, using the CliniMACS® CD34 Reagent System, prior to infusion.

Busulfan

Busulfan is a cell cycle non-specific alkylating antineoplastic agent, in the class of alkyl sulfonates. Patients will receive low-dose busulfan conditioning targeted over 2 days to achieve a cumulative area under the curve (AUC) of 20 mg\*hr/L.

Primary outcome measure

  • To demonstrate that ART-SCID patients receiving AProArt-CD34 infusion have superior overall survival (OS) at 24 months post treatment with AProArt-CD34 versus the established outcome of 0% OS for patients who receive no treatment for ART-SCID [ Time Frame: 24 months ]

Central Contacts and Locations

Central contacts

Morton Cowan, MD

415-476-2188Mort.Cowan@ucsf.edu

Jennifer Puck, MD

415 502-2090Jennifer.Puck@ucsf.edu

Locations

University of California, San Francisco (UCSF) Children's Hospital

Recruiting

San Francisco, California, United States, 94143

More Information

Sponsor

University of California, San Francisco

Last update posted

Feb 13, 2026

Last verified

Feb, 2026

Keywords

  • Artemis-deficient Severe Combined Immunodeficiency
  • gene therapy
  • autologous stem cell transplant

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of California, San Francisco on 2026-02-13.