RecruitingPhase 1/2

Autologous Gene Therapy for Artemis-Deficient SCID

United States24 participantsStarted 2018-05-31

Plain-language 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.

Who can participate

Age range2 Months

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 *…

What they're measuring

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

Timeframe: 24 months

Trial details

NCT IDNCT03538899

SponsorUniversity of California, San Francisco

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2038-06

Contact for this trial

Morton Cowan, MD

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