Studium antigeni receptoris lymphocytis T (car-T) in curatione lymphomatis relapsi et refractorii non-Hodgkin

Enarratio:

Hoc centrum est unius, unius brachii, titulus aperta studii. Cum eligibilitatem indiciis occurrentibus et in probatione scribentibus, aegroti leukapheresim subibunt pro collectione lymphocytarum autologorum. Postquam cellulae fabricatae sunt, aegroti ad chemotherapyam lymphodeplendam cum cyclophosphamide et fludarabino procedent per dies continuos 1-2 dies consecutus infusionem car T-cellarum ad scopum dosis cellularum 3-10×105/kg.

criteria

Criteria inclusion:

1. CD19-positivum Hodgkin scriptor non-lymphoma 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 tuberculum 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: pallium cellula lymphoma. 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. Aetas ≥18 annorum (inclusa limen);
3. Secundum 2014 Lugano criteriis versio, una saltem laesio mensurabilis mensurabilis est ut basis aestimationis: nam laesiones intranodales definitur esse: longi diametri >1.5cm; ad laesiones extranodales, longi diametri >1.0cm;
4. Eastern Cooperative Oncology Group actio status score ECOG score 0-2;
5. Accessus venarum ad collectionem requisitus constitui potest, et satis sunt cellulae apheresis non mobiles collectae pro productione cellae CAR-T;
6. Munus iecoris et renis, munus cardiopulmonale dignum sequentibus requisitis;
   • Serum creatinine≤2.0×ULN;
   • Sinistra eiectio ventriculi ≥% fractio et nulla effusio pericardialis manifesta, nulla ECG abnormis;
   • Sanguinis oxygeni satietatem ≥92% in statu non-oxygeni;
   • Sanguis totalis bilirubin≤2.0×ULN (exceptis sine significatione clinica);
   • ALT et AST≤3.0×ULN (tumore hepatis infiltration≤5.0×ULN);
7. Poterit intelligere et voluntarie consensum informatum subscribere.

Criteria exclusio:

1. CAR-T therapia vel alia therapia cellularum gene-mutata antequam protegendo accepit;
2. Theraphim anti-tumorem receptum (praeter systemicum immune LAPIS inhibitionis vel excitationis therapiae) intra 2 septimanas vel 5 dimidiatas (quodlibet brevius est) ante protegendo. 3 dimidium-vitae scribendae requiruntur (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 receptor agonist, 4-1BB receptor agonist, etc.);
3. Qui cellam transplantationem hematopoieticam caulis (ASCT) intra 12 septimanas ante apheresin acceperunt, vel qui ante allogeneicum hematopoieticum truncum cellam transplantationem (HSCT) acceperunt, vel qui transplantationem organi solidi habent; immunosuppressio intra 2 septimanas ante apheresim Gradus 2 et supra GVHD medicamenti requiritur;
4. Aegris cum implicatione lymphoma atriali vel ventricularis vel urgente curatione indigent ob massam tumorem, sicut obstructionem intestinalem vel compressionem vascularium;
5. Vaccinati sunt cum vaccino vivo attenuato intra 6 septimanas ante lepram purgandam;
6. Accidens cerebrovascularis vel epilepsia intra 6 menses ante signationem ICf occurrit;
7. Historia myocardialis infarctionis, cardiacis bypass vel stent, angina instabilis vel alii machinis cordi significantes morbi cordis intra 12 menses ante Icf signandi;
8. Agentes vel impotentes morbi autoimmunes (ut Morbus Crohn, arthritis rheumatoideus, systemicus lupus erythematosus), iis exceptis quae curationem systemicam non requirunt;
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. Incontinens infectio intra hebdomadam I ante protegendo;
11. Hepatitis B superficies antigenis (HBsAg) seu hepatitis B nucleus anticorpus (HBcAb) positivus et periphericus sanguinis hepatitis B virus (HBV) DNA titer detectio major est quam range normali referendi; vel hepatitis C virus (HCV) anticorpus positivum et periphericum sanguinis C Virus Hepatitis (HCV) RNA test titer maior est quam range normali referendi; vel immuno-fietatem humanam (HIV) antibody positive; vel syphilis test affirmativa; cytomegalovirus (CMV) DNA test positivum;
12. Mulieres gravidae vel ubere; vel mulieres de aetate partus, quae graviditatem positivum test in tempus protegendo habent; vel aegros vel masculum vel feminam, qui contraceptionem uti nolint a tempore signandi consensus informati forma ad 1 annum post receptam CAR-T cellam infusionem;
13. Alii investigatores alienum esse censent studio participare.