Wiskott-Aldrich Sendromu İçin Hematopoietik Kök Hücre Gen Aktarımının Pilot ve Uygulanabilirlik Çalışması

Sade dilde özet

Wiskott-Aldrich sendromu (WAS), X kromozomu üzerindeki genetik bir bozukluk nedeniyle erkek çocukları etkileyen kalıtsal bir kan ve kemik iliği hastalığıdır; kanamayı durduran trombositler hem az sayıdadır hem de düzgün çalışmaz, bağışıklık hücreleri de yeterince işlev görmez. Bu nedenle çocuklarda ciddi kanama, enfeksiyon, egzama, artrit ve lenfoma riski artar. Faz 1/2 (Phase 1/2) çalışma, retrovirüs aracılı gen aktarımını değerlendirmekte olup DNA dizilemesiyle tanısı doğrulanmış, 3 ay-35 yaş arası ve uygun doku uyumlu (HLA) verici bulunamayan katılımcıları kapsamaktadır.

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

Deney bilgileri

Faz

PHASE1/PHASE2

Durum

Tamamlandı

Sponsor

David Williams

Müdahale

Retrovirus-mediated gene transfer

Başlangıç

01.07.2011

Tahmini bitiş

01.09.2024

Ülkeler

United States

İlgili genler

Merkezler

• Boston, United States

Uygunluk kriterleri

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

Inclusion Criteria:

1. Confirmed molecular diagnosis by DNA sequencing and either

   1. absence of the WAS protein by flow cytometry OR
   2. clinical score 3-5
2. Age 3 months to 35 years
3. For subjects \< 5 years of age:

   1. Lack of HLA-genotypically identical bone marrow donor.
   2. Lack of a 9/10 or 10/10 molecularly HLA-matched unrelated donor after 3 months of searching.
   3. Lack of a 6/6 molecularly HLA-matched cord blood donor of adequate cell number after 3 months of searching
4. For subjects 5 years of age or older:

   a.Lack of HLA-genotypically identical bone marrow donor.
5. Subjects who have undergone allogeneic transplant previously must additionally have:

   1. Failure defined as \<5% donor T cell engraftment and
   2. Contraindication to re-use of the same donor due to severe GVHD or non-availability.
6. Parental/guardian/patient signed informed consent
7. Willingness to return for follow-up during the 5 year study period.
8. Adequate organ function and performance status

   1. Performance status ≥50% (Lansky play for age \<16 years, Karnofsky for age ≥16 years)
   2. Left ventricular ejection fraction \>40% or shortening fraction \>25%
   3. Bilirubin ≤ 2.0 mg/dL
   4. Measured creatinine clearance or GFR by nuclear medicine study ≥40 ml/min/1.73 m2
   5. DLCO (corrected for hemoglobin), FEV1, FVC \>50% of predicted; if age \< 7 years, then oxygen saturation \>92% on room air

Exclusion Criteria:

1. Contraindication to bone marrow harvest, or to administration of conditioning medication.
2. Known positive HIV serology or HIV nucleic acid testing.
3. Other uncontrolled infection.
4. Active malignancy other than EBV lymphoproliferative disease.
5. Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenetics
6. Congenital cardiac disease with congestive heart failure
7. Oxygen dependence at baseline
8. Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful study completion. This may include but is not limited to:

   * Severe deterioration of clinical condition after collection of cells but before infusion of transduced cells
   * Documented refusal or inability of the family to return for scheduled visits
   * Other concerns about unwillingness or inability to comply with protocol requirements
   * Unforeseen rare circumstances such as sudden loss of legal guardianship