Artemis Eksikliğine Bağlı SCID için Otolog Gen Terapisi

Sade dilde özet

Bu çalışma, Artemis eksikliğine bağlı ağır kombine immün yetmezlik (severe combined immunodeficiency, SCID) olan hastalarda, hastanın kendi kök hücrelerinin genetik olarak düzeltilmesine dayanan bir gen terapisini (AProArt-CD34) incelemektedir. Çalışmaya, DCLRE1C geninde iki alelde de hastalık yapıcı mutasyon bulunan, en az 2 aylık bebekler katılmaktadır. Çalışma Faz 1/Faz 2 aşamasında yürütülmekte ve halen katılımcı almaktadır.

Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.

Deney bilgileri

Faz

PHASE1/PHASE2

Durum

Katılımcı alıyor

Sponsor

University of California, San Francisco

Müdahale

AProArt-CD34, CliniMACS® CD34 Reagent System cell sorter device, Busulfan

Başlangıç

31.05.2018

Tahmini bitiş

01.06.2038

Ülkeler

United States

İlgili genler

Merkezler

• San Francisco, United States

Uygunluk kriterleri

Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.

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.