Ulikan ngeunaan limfosit T reséptor antigen chimeric (CAR-T) dina pengobatan limfoma non-Hodgkin kambuh sareng refractory.

Katerangan Terperinci:

Ieu mangrupikeun pusat tunggal, panangan tunggal, ulikan labél kabuka. Saatos nyumponan kriteria eligibility sareng ngadaptar dina uji coba, pasien bakal ngalaman leukapheresis pikeun ngumpulkeun limfosit autologous. Sakali sél geus dijieun, penderita lajeng bakal neruskeun lymphodepleting kémoterapi kalawan cyclophosphamide na fludarabine pikeun 1-2 poé padeukeut dituturkeun ku infusion of CAR T-sél dina dosis target 3-10 × 105 sél / kg.

kriteria

Kriteria inklusi:

1. CD19-positive limfoma non-Hodgkin confirmed by cytology or histology according to WHO2016 criteria:
   1. Diffuse large B-cell lymphoma: including unspecified (DLBCL, NOS), chronic inflammation-related DLBCL, primary cutaneous DLBCL (leg type), EBV-positive DLBCL (NOS); and high-grade B-cell lymphoma (including high-grade B-cell lymphoma, NOS, and high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements); and primary mediastinal large B-cell lymphoma; and T-cell-rich histiocytosis B-cell lymphoma; and transformed DLBCL (such as follicular lymphoma, chronic lymphocytic leukemia/small B-lymphocytic lymphoma transformed DLBCL); patients with the above tumor types have been treated with at least first- and second-line drugs and have stable disease for ≤12 months , or when the best Disease progression after efficacy; or disease progression or relapse after autologous stem cell transplantation ≤12 months;
   2. According to WHO2016 criteria cytology or histology confirmed CD19 positive: follicular cell lymphoma. Patients with this tumor type have received at least third-line therapy, and recurrence or disease progression has occurred within 2 years after third-line therapy or more. Currently in disease progression, stable disease, or partial remission;
   3. According to WHO2016 standard cytology or histology confirmed CD19 positive: limfoma sél mantel. Such patients have not been cured or relapsed after at least three-line treatment and are not suitable for stem cell transplantation or relapse after stem cell transplantation;
2. Umur ≥18 taun (kaasup bangbarung);
3. Numutkeun kritéria Lugano versi 2014, sahenteuna aya hiji lesi anu tiasa diukur dua diménsi salaku dadasar évaluasi: pikeun lesi intratranodal, diartikeun salaku: diaméter panjang > 1.5cm; pikeun lesi extranodal, diaméterna panjang kedah > 1.0cm;
4. Skor status aktivitas Grup Onkologi Koperasi Wétan Skor ECOG 0-2;
5. The aksés venous diperlukeun pikeun ngumpulkeun bisa ngadegkeun, tur aya cukup sél dikumpulkeun ku apheresis non-mobilized pikeun produksi sél CAR-T;
6. Fungsi ati jeung ginjal, fungsi cardiopulmonary minuhan sarat di handap ieu:
   • Kréatinin sérum≤2.0×ULN;
   • Fraksi ejection ventricular kénca ≥ 50% tur euweuh effusion pericardial atra, euweuh ECG abnormal;
   • jenuh oksigén getih ≥92% dina kaayaan non-oksigén;
   • Total bilirubin getih≤2.0×ULN (iwal tanpa significance klinis);
   • ALT sareng AST≤3.0×ULN (kalayan infiltrasi tumor ati≤5.0×ULN);
7. Bisa ngarti tur sukarela nandatanganan idin informed.

Kriteria Pangaluaran:

1. Narima terapi CAR-T atawa terapi sél gén-dirobah séjén saméméh screening;
2. Narima terapi anti tumor (iwal inhibisi pos pemeriksaan imun sistemik atawa terapi stimulasi) dina 2 minggu atawa 5 satengah hirup (mana nu leuwih pondok) saméméh screening. 3 satengah hirup diwajibkeun pikeun ngadaptar (contona, ipilimumab, nivolumab, pembrolizumab, atezolizumab, agonis reséptor OX40, agonis reséptor 4-1BB, jsb.);
3. Jalma anu geus narima cangkok sél stém hematopoietic (ASCT) dina 12 minggu saméméh apheresis, atawa anu saméméhna geus narima allogeneic cangkok sél stém hematopoietic (HSCT), atawa jalma anu boga cangkok organ padet; imunosupresi diperyogikeun dina 2 minggu sateuacan apheresis Kelas 2 sareng saluhureun GVHD obat;
4. Pasén kalawan involvement lymphoma atrium atanapi ventricular atanapi peryogi perlakuan urgent alatan massa tumor kayaning halangan peujit atawa komprési vascular;
5. Geus divaksinasi ku vaksin hirup attenuated dina 6 minggu saméméh clearing kusta;
6. kacilakaan cerebrovascular atanapi epilepsy lumangsung dina 6 bulan saméméh Signing nu ICF;
7. Riwayat infark miokard, bypass jantung atanapi stent, angina teu stabil atanapi panyakit jantung anu signifikan sacara klinis dina 12 bulan sateuacan ngadaptarkeun ICF;
8. Panyakit otoimun anu aktip atanapi teu terkendali (sapertos panyakit Crohn, rematik rheumatoid, lupus erythematosus sistemik), iwal anu henteu ngabutuhkeun perawatan sistemik;
9. Malignant tumors other than non-Hodgkin lymphoma within 5 years prior to screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, Ductal carcinoma in situ;
10. Inféksi anu teu terkendali dina 1 minggu sateuacan saringan;
11. Antigen permukaan Hépatitis B (HBsAg) atanapi antibodi inti hépatitis B (HBcAb) positip sareng virus hépatitis B getih periferal (HBV) deteksi titer DNA langkung ageung tibatan rentang rujukan normal; atawa hépatitis C virus (HCV) antibodi positif jeung getih periferal C virus Hépatitis (HCV) RNA titer test leuwih gede ti rentang rujukan normal; atawa human immunodeficiency virus (HIV) antibodi positif; atawa tés sipilis positif; tes DNA cytomegalovirus (CMV) positip;
12. Awéwé anu reuneuh atawa breastfeeding; atawa awéwé umur ngalahirkeun anu boga test kakandungan positif salila periode screening; atanapi pasien lalaki atanapi awéwé anu henteu daék nganggo kontrasépsi ti waktos nandatanganan formulir idin informed ka 1 taun saatos nampi infus sél CAR-T;
13. Panalungtik séjén nganggap éta pantes pikeun ilubiung dina pangajaran.