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A Phase I/II Study of Gene-modified WT1 TCR Therapy in MDS & AML Patients
Bu çalışma, hastanın kendi T hücrelerinin WT1 hedefli bir T hücre reseptörü (TCR) ile genetik olarak değiştirildiği bir gen modifiyeli hücre tedavisini incelemiştir. Çalışmaya, hipometilleyici ilaç tedavisi almış ve hastalığı devam eden ya da nükseden, miyelodisplastik sendrom (MDS) veya akut miyeloid lösemi (AML) tanılı, HLA-A*0201 pozitif yetişkin hastalar alınmıştır. Çalışma Faz 1/Faz 2 aşamasında yürütülmüş ve tamamlanmıştır.
Yukarıdaki özet, resmî kaydın sade dile aktarılmış halidir. Orijinal İngilizce başlık referans için gösterilir.
Kriterler ClinicalTrials.gov kaydından orijinal İngilizce haliyle alınmıştır. Uygunluk kararını yalnızca deneyi yürüten ekip verebilir.
Key Inclusion criteria:
* The trial will recruit subjects with MDS or AML who have received hypomethylating agent therapy (at least 6 cycles of azacitidine or 4 cycles of decitabine), and are EITHER:
* Relapsed, defined as failing to maintain an initial IWG response
OR
• Stable, defined as failing to achieve an IWG response
Subjects who have received hypomethylating agent therapy as part of a combination regimen may be eligible after discussion with the Sponsor.
1. Subjects aged 18 years or older who have a diagnosis of, EITHER:
* MDS with an IPSS of intermediate -2, or high and one of the following FAB types:
* Refractory anaemia with excess blasts (RAEB)
* Chronic myelomonocytic leukaemia (CMML) with at least 10% bone marrow blasts (WHO CMML II) OR
* AML (diagnosed according to WHO classification 2008 revision)
2. Subjects with documented HLA-A\*0201 positive serotype
3. Subjects with less than 30 per cent bone marrow blasts
4. Subjects with relapsed disease must have less than 5 per cent peripheral blasts
5. Subjects with stable disease must have less than 10 per cent peripheral blasts
6. Subjects with less than a doubling of bone marrow blast count between the start of hypomethylating agent therapy and the date of screening
7. Subjects to complete screen 1 visit within a minimum of 28 days and maximum of 90 days since completion of azacitidine or decitabine therapy. Subjects who have exceeded the 90 day window may be eligible after discussion with the Sponsor.
8. Subjects with ECOG status 0, 1 or 2
9. Subjects who have at least one cytopenia (ANC \<1000/μL, platelet count \<75,000/μL, Hgb \<11g/dL or RBC transfusion dependence)
Key Exclusion criteria:
improvement or molecular response following azacitidine treatment
* CMML patients who have a white blood cell count \> 13 x 109/L
* Acute promyelocytic leukaemia (FAB M3 Classification)
* Uncontrolled intercurrent illness
* Active malignancy, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
* Known history of Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV) or Hepatitis B virus (HBV) or positive for Human T-Lymphocyte Virus (HTLV) or Syphilis. • Active auto-immune disease
* Clinically significant non-hematologic toxicity after prior therapy chemotherapy higher than grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) (v 4.0)
* Subjects who require haemodialysis or peritoneal dialysis
* Pregnant and lactating women
* Subjects unwilling or unable to use adequate contraceptive precautions at screening and throughout the trial
* Subjects who have undergone major surgery without full recovery within last 28 days prior to screening
* Subjects with known hypersensitivity to cyclophosphamide, fludarabine, methylprednisolone or IL-2 (Interleukin-2)