Nazarin chimeric antigen receptor T lymphocytes (CAR-T) a cikin jiyya na relapsed da refractory non-Hodgkin lymphoma

Cikakken Bayani:

Wannan bincike ne na tsakiya guda, hannu ɗaya, buɗaɗɗen lakabi. Bayan saduwa da ka'idojin cancanta da yin rajista a kan gwaji, marasa lafiya za su sha leukapheresis don tarin ƙwayoyin lymphocytes na autologous. Da zarar an ƙera sel, marasa lafiya za su ci gaba da yin amfani da chemotherapy na lymphodepleting tare da cyclophosphamide da fludarabine na kwanaki 1-2 a jere tare da jiko na CAR T-cell a wani nau'i na 3-10 × 105 sel / kg.

sharudda

Ka'idodin Hadawa:

1. CD19-positive ba Hodgkin 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 tumo 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 linzoma. 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: maganin sutturar ƙwayar sel. 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. Shekaru ≥18 shekaru (ciki har da bakin kofa);
3. Dangane da sigar Lugano na 2014, akwai aƙalla raunin auna ma'auni guda biyu a matsayin tushen kimantawa: don raunin intranodal, an bayyana shi azaman: tsayin diamita> 1.5cm; don raunuka na waje, tsayin diamita ya kamata ya zama> 1.0cm;
4. Matsayin ayyukan ƙungiyar haɗin gwiwar Oncology na Gabas makin ECOG 0-2;
5. Za a iya kafa hanyar samun venous da ake buƙata don tarawa, kuma akwai isassun ƙwayoyin da aka tattara ta hanyar apheresis marasa motsi don samar da ƙwayoyin CAR-T;
6. Ayyukan hanta da koda, aikin zuciya na zuciya sun cika waɗannan buƙatu:
   • Serum creatinine≤2.0 × ULN;
   • Juzu'i na fitarwa na ventricular hagu ≥ 50% kuma babu fitowar bugun pericardial, babu ECG mara kyau;
   • Jiki oxygen jikewa ≥92% a cikin wadanda ba oxygen jihar;
   • Jimlar jinin bilirubin≤2.0 ×ULN (sai dai ba tare da mahimmancin asibiti ba);
   • ALT da AST≤3.0 × ULN (tare da ciwon hanta infiltration≤5.0 × ULN);
7. Samun ikon fahimta da sa hannu da son rai akan sanarwar da aka sanar.

Ka'idojin keɓewa:

1. Karɓi maganin CAR-T ko wasu hanyoyin maganin tantanin halitta da aka gyara kafin nunawa;
2. Karɓi maganin ƙwayar cuta (sai dai hanawa na rigakafi na tsarin rigakafi ko maganin ƙarfafawa) a cikin makonni 2 ko rabi na 5 (duk wanda ya fi guntu) kafin dubawa. Ana buƙatar rabin rayuwar 3 don yin rajista (misali, ipilimumab, nivolumab, pembrolizumab, atezolizumab, agonist mai karɓar mai karɓa na OX40, 4-1BB agonist receptor, da sauransu);
3. Wadanda suka karbi dashen kwayar cutar hematopoietic (ASCT) a cikin makonni 12 kafin apheresis, ko kuma wadanda suka karbi allogeneic hematopoietic stem cell transplantation (HSCT), ko wadanda ke da dashen gabobin jiki; Ana buƙatar rigakafin rigakafi a cikin makonni 2 kafin apheresis Grade 2 da sama da GVHD na miyagun ƙwayoyi;
4. Marasa lafiya tare da shigar da lymphoma na atrial ko ventricular ko kuma suna buƙatar magani na gaggawa saboda yawan ƙwayar cuta kamar toshewar hanji ko matsawar jijiyoyin jini;
5. An yi allurar riga-kafi da allurar rigakafin rayuwa a cikin makonni 6 kafin a kawar da kuturta;
6. Cerebrovascular hatsari ko farfadiya ya faru a cikin watanni 6 kafin sanya hannu kan ICF;
7. Tarihin ciwon zuciya na zuciya, bugun zuciya ko stent, angina maras tabbas ko wasu cututtukan zuciya na asibiti a cikin watanni 12 kafin shiga ICF;
8. Cututtuka na autoimmune masu aiki ko marasa sarrafawa (kamar cutar Crohn, rheumatoid arthritis, lupus erythematosus na yau da kullun), sai waɗanda ba sa buƙatar magani na tsari;
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. Cutar da ba za a iya sarrafawa ba a cikin mako 1 kafin nunawa;
11. Hepatitis B surface antigen (HBsAg) ko Hepatitis B core antibody (HBcAb) tabbatacce kuma na gefe na jini hepatitis B cutar (HBV) DNA titer gane ya fi na al'ada tunani kewayon; ko cutar hanta ta C (HCV) antibody tabbatacce da na gefe jini C Kwayar cutar hanta (HCV) RNA titer gwajin ya fi girma na al'ada; ko kwayar cutar rigakafi ta mutum (HIV) tabbatacce; ko gwajin syphilis tabbatacce; cytomegalovirus (CMV) gwajin DNA tabbatacce;
12. Mata masu ciki ko masu shayarwa; ko matan da suka kai shekarun haihuwa waɗanda ke da gwajin ciki mai kyau a lokacin gwajin; ko maza ko mata marasa lafiya waɗanda ba sa son yin amfani da maganin hana haihuwa daga lokacin sanya hannu kan takardar izinin da aka sanar zuwa shekara 1 bayan samun jiko tantanin halitta CAR-T;
13. Sauran masu binciken suna ganin bai dace a shiga cikin binciken ba.