CD19 CAR-T Cell Therapy for Relapsed/Refractory B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia
A Phase I Clinical Trial of Anti-CD19 Chimeric Antigen Receptor With Synthetic Biology Optimizing Nano-vector T Cells Injection for Subjects With Relapsed/Refractory/High-risk B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia
Lead SponsorKunming Medical University
Indication/ConditionB Cell Lymphoma B-cell Acute Lymphoblastic Leukemia
Intervention/TreatmentAnti-CD19 CAR-T Cells Injection
The primary objective of this study is to evaluate the safety and clinical activity of anti-CD19 Chimeric Antigen Receptor T cells (KD-019 CAR-T)infusion in the treatment of relapsed/refractory B-cell Lymphoma and B-cell acute lymphoblastic leukemia （B-ALL）.
The investigators designed an KD-019 Chimeric Antigen Receptor(CAR) with FMC63 single-chain antibody fragment (Scfv). This CAR has a CD8 hinge and transmembrane domains and a 4-1BB costimulatory domain; T cells expressing this CAR release relatively low levels of cytokines. Subjects with relapsed/refractory CD19-positive B-cell Lymphoma and B-ALL can participate if all eligibility criteria are met. Subjects receive chemotherapy prior to the infusion of KD-019 CAR-T cells. After the infusion, subjects will accept follow-up for side effects and effect of KD-019 CAR-T cells by the sponsor. Study procedures may be performed while hospitalized.
Autologous genetically modified anti-CD19 CAR transduced T cells
Dosage form：injection Dosage:1-5x10^6/kg, 70ml/time, The CAR-T cells will be administered by i.v. injection over 20-30 minutes Frequency: total one time
Inclusion Criteria: Patients or their legal guardians voluntarily participate and sign the Informed Consent Document; 18 Years and older, Male and female; Pathologically and histologically confirmed CD19 + B cell tumors; Patients currently have no effective treatment options, such as chemotherapy or relapse after hematopoietic stem cell transplantation; Or patients voluntarily choose transfusion of anti-CD19 CAR-T cells as the first treatment program; B-cell tumors / lymphomas and B-cell acute lymphoblastic leukemia include the following four types: B-cell acute lymphoblastic leukemia; Indolent B-cell lymphomas; Aggressive B-cell lymphoma; 4、 Subjects: (1) Residual lesions remain after treatment; (2) Not suitable for Hematopoietic stem cell transplantation (auto/allo-HSCT); (3) Relapse after Complement receptor 1 (CR1) and unsuitable for HSCT; (4) Patients with high risk factors; (5) Relapse or no remission after hematopoietic stem cell transplantation or cell immunotherapy. 5、 Have measurable or evaluable tumor foci; 6、 Liver, kidney and cardiopulmonary functions meet the following requirements: Serum glutamic pyruvic transaminase (ALT) and serum glutamic oxaloacetic transaminase (AST) <3 ×upper limit of normal (ULN); Total bilirubin ≤34.2μmol/L; Serum creatinine<220μmol/L; Baseline oxygen saturation≥95%; Left ventricular ejection fraction（LVEF）≥40%. 7、 Subjects who did not receive Chemotherapy, Radiotherapy, Immunotherapy (immunosuppressive drugs) or other treatment within 4 weeks prior to enrollment; Relevant toxicity≤1 grade before enrollment (except for low toxicity such as hair loss); 8、Peripheral superficial venous blood flow is smooth, which can meet the needs of intravenous drip; 9、Clinical performance status of eastern cancer cooperation group (ECOG) score ≤2，Expected survival≥3 months; Exclusion Criteria: Pregnant (urine/blood pregnancy test positive) or lactating women; Planned pregnancy during treatment or within 1 year after treatment, or a male subject whose partner plans pregnancy within 1 year of their cell transfusion; Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment; Active or uncontrollable infection within four weeks prior to enrollment; Patients with active hepatitis B/C; HIV-infected patients; Severe autoimmune or immunodeficiency disorders; Patients are allergic to macromolecule drugs such as antigens or cytokines; Subjects participated in other clinical trials within 6 weeks before enrollment; Systematic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones); Mental illness; Drug abuse/addiction; The investigators consider other conditions unsuitable for enrollment.