Gene therapy for treating Artemis-deficient Severe Combined Immunodeficiency

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This study aims to treat Artemis-deficient Severe Combined Immunodeficiency (ART-SCID) by transferring a normal copy of the DCLRE1C gene into the patient's own stem cells. Participants will undergo a conditioning regimen with sub-ablative busulfan before receiving an infusion of gene-corrected stem cells. The trial will assess the safety and efficacy of this approach in providing a normal immune system. A total of 24 newly diagnosed patients will be enrolled at the University of California San Francisco and followed for 15 years post-infusion.

Why it matters

Who can join: the full rules

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.

Where it's running

• University of California, San Francisco (UCSF) Children's Hospital
  San Francisco, California, United States Recruiting

Study contacts

• Principal investigator: Morton Cowan, MD — University of California, San Francisco
• Study coordinator: Morton Cowan, MD
• Email: Mort.Cowan@ucsf.edu
• Phone: 415-476-2188

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.