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CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell Acute Lymphoblastic Leukemia (ALL)
Bu çalışma, B hücreli akut lenfoblastik lösemi (acute lymphoblastic leukemia) olan hastalarda AUTO3 adlı CD19/22 CAR T hücre tedavisini incelemektedir. Nüksetmiş (relapse) veya tedaviye dirençli yüksek riskli hastalığı olan, 1-24 yaş arası hastalar için tasarlanmıştır. 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:
1. Male or female patients aged 1-24 years with high risk (HR) relapsed/refractory B-lineage ALL, AND:
1. Any bone marrow (BM) relapse or central nervous system (CNS) relapse with detectable BM disease after allogeneic stem cell transplant (SCT) and must be ≥6 months from SCT at the time of AUTO3 infusion; OR,
2. HR first relapse; OR,
3. Standard risk relapse patients with HR cytogenetics; OR,
4. Second or greater relapse; OR,
5. BM minimal residual disease (MRD) ≥10-³ prior to planned SCT; OR,
6. Any on-treatment relapse in patients aged 16-24 years.
(Phase II Only - Criteria in addition to those described above:)
7. Primary refractory disease; OR,
8. Patients with Philadelphia chromosome positive ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor (TKI) therapy, or if TKI therapy is contraindicated; OR,
9. Isolated CNS relapse but with ≤CNS Grade 2 disease at time of enrolment.
2. Documentation of CD19 and or CD22 expression on leukaemic blasts in the BM, peripheral blood, or cerebrospinal fluid within 3 months of screening.
3. Detectable disease in the BM at a level ≥10-⁴ (Phase I only).
4. Absolute lymphocyte count ≥0.5 x 10⁹/L.
5. Adequate renal, hepatic, pulmonary, and cardiac function.
6. Karnofsky (age ≥10 years) or Lansky (age \<10 years) score ≥50%.
7. Willing and able to give written, informed consent to the current study (patient and/or parent or legal guardian).
Exclusion Criteria:
1. Isolated extra-medullary disease relapse.
2. Active CNS involvement of ALL (CNS Grade 3 per National Comprehensive Cancer Network guidelines).
3. Active infectious bacterial or viral disease requiring IV anti-microbials for treatment.
4. Females who are pregnant or lactating.
5. Females of child-bearing potential and post pubertal male participants who are unwilling to use highly effective methods of contraception for a period of 1 year after the AUTO3 infusion.
6. Inability to tolerate leukapheresis.
7. Prior CD19 or CD22 targeted therapy with Grade 4 toxicity or ≥refractory Grade 3 cytokine release syndrome (CRS) or ≥Grade 3 drug related CNS toxicity.
8. Pre-existing significant neurological disorder.
9. Stem Cell Transplant patients only: active significant acute graft versus host disease (GVHD) or moderate/severe chronic GVHD requiring systemic steroids or other immunosuppressant within 4 weeks of enrolment.
10. The following medications are excluded:
1. Steroids: Therapeutic doses of steroids must be stopped \>72 hours prior to AUTO3 infusion and leukapheresis. However, physiological replacement doses of steroids are allowed: \<12 mg/m2/day hydrocortisone or equivalent.
2. Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed \>6 weeks prior to AUTO3 infusion.
3. Graft versus host disease therapies: Any drug used for GVHD must be stopped \>4 weeks prior to AUTO3 infusion.
4. Chemotherapy: Should be stopped 1 week prior to leukapheresis and 2 days prior to starting pre-conditioning chemotherapy.
11. Known allergy to albumin, dimethyl sulfoxide, cyclophosphamide or fludarabine.
For AUTO3 Infusion: Patients meeting any of the following exclusion criteria will not be treated with AUTO3 or treatment will be delayed until they no longer meet these criteria:
1. Severe intercurrent infection.
2. Requirement for supplementary oxygen.
3. Allogeneic transplant recipients with active significant acute GVHD overall Grade ≥II or moderate/severe chronic GVHD requiring systemic steroids.