Safety and Efficacy Evaluation of CD19-UCART

A Safety and Efficacy Study of CD19-UCART (Allogeneic Engineered T-cells Expressing Anti-CD19 Chimeric Antigen Receptor) in Patients With Relapsed or Refractory B-cell Hematologic Malignancies

The First Affiliated Hospital of Zhengzhou University, First Affiliated Hospital of Zhejiang University, Second Xiangya Hospital of Central South University

The purpose of this study is to evaluate the safety and efficacy of ascending doses of CD19-UCART in patients with relapsed or refractory B-cell hematological malignancies.

CD19-UCART is a kind of "off-the-shelf" product originated from health donor's PBMC.This is a open-label, dose estilation study to evaluate the safety and anti-tumor efficacy of CD19-UCART in the treatment of relapsed or refractory B-cell hematological malignancies.

All patients will be treated with 1 injection of CD19-UCART. Three escalating dose-levels (1.0-2.0x10^6/kgBW, 2.5-5.0x10^6/kgBW, 5.5-10.0x10^6/kgBW) of CD19-UCART will be evaluated using a 3+3 design. Each CD19-UCART injection will be administered at Day 0.

A conditioning therapy with cyclophosphamide and fludarabine will be conducted before CD19-UCART injection. VP16 can be added to the conditioning therapy.

The total response rate after 90 days of treatment with study drug (overall response rate for ALL= CR+CRi; for NHL=CR+PR);

Inclusion Criteria: Voluntarily participating in this clinical study and signing the informed consent form; The estimated survival period is at least one month; No other serious cardiopulmonary diseases, and normal liver and kidney functions (except for subjects with tumor lesions in their liver and kidneys); Failure of T cell isolation during autologous CART preparation or failure of CART amplification or failure to complete apheresis or disease progression resulting in patients not benefiting from autologous CAR-T cell therapy; Or: T cell percentage in PBMC of peripheral blood ≤ 10%; Or the disease is not effectively controlled within one month after autologous CAR-T transfusion, and the patient cannot receive CAR-T transfusion again; Flow cytometry within two months demonstrated positive expression of CD19 in the tumor (positive rate 50%-90%; Or biopsy ≥ 50% within 6 months; Or obtaining a biopsy again); Hematological indicators: 1) WBC count ≥ 1.5× 10^9/L; Absolute value of neutrophils ≥ 0.8× 10^9/L; Lymphocyte count ≥0.1×10^9/L;2) Hemoglobin ≥ 60g/L;3) Platelet count ≥20×10^9/L; Biochemical indicators (except for subjects with tumor foci in liver and kidney): Total bilirubin (TBIL)≤1.5 times the Upper Limits of Normal (ULN); AST and ALT≤1.5 *ULN; Scr and BUN)≤1.5*ULN; Biochemical indicators in subjects with liver and kidney invasion should meet: Total bilirubin (TBIL)≤5 *ULN;AST and ALT≤5*ULN; Scr and BUN ≤ 5*ULN; Cardiac function: Good hemodynamic stability, and the left ventricular ejection fraction (LVEF) ≥ 55%; Serum viral EBV-DNA, CMV-DNA, HIV antibody and syphilis antibody, HBV, HCV virus quantification were all negative; ECOG activity status score: 0-2 points; Female subjects must have access to effective contraceptive measures (e.g., oral prescription contraceptives, injectable contraceptives, intrauterine devices, double blocking, contraceptive patches, male partner sterilizations) throughout the study period; Serum or urine pregnancy test results must be negative at screening and throughout the study; Willing to comply with the rules established in this protocol; Patients with relapsed/refractory CD19-positive acute B-cell leukemia (B-ALL, with the age of 1-60 years) or relapsed/refractory B-cell non-Hodgkin's lymphoma (B-NHL, with the age of 5-65 years). Exclusion Criteria: Pregnant or lactating women; The following drugs or treatments should be excluded:High-dose glucocorticoids were used within 72h prior to UCAR-T infusion, except for physiological alternative therapies;Allogeneic cell therapies such as donor lymphocyte transfusion within 6 weeks prior to UCAR-T transfusion;GVHD treatment; Single extramedullary relapse B-ALL; Suffering from severe mental disorder; Active autoimmune diseases requiring immunotherapy; History of other malignant tumors; Patients with severe cardiovascular disease; Organ function is in the following abnormalities; Total bilirubin > 1.5 times the upper limit of normal unless the patient is Gilbert's syndrome; Partial thromboplastin time or activated partial thromboplastin time or international normalized ratio >1.5*ULN；in the absence of anticoagulant therapy; There is an active infectious disease or any major infectious event requiring high-level antibiotics; Any condition that, in the opinion of the investigator, may increase the subject's risk or interfere with the test results.