novel anti-cd19 universal car-t cells for r/r cd19+ b-all

Conditions: B-cell Acute Lymphoblastic Leukemia; B-ALL

Summary: this is a single-arm, single-center, open-labeled clinical study to evaluate the safety and efficacy of ucar-t cells injection for patients with relapsed/refractory(r/r) b-cell acute lymphoblastic leukemia(b-all).

although the anti-cd19 car-t cell therapies have gained significant clinical outcome in patients with r/r b-all，autologous car-t is not feasible for some patients. to make further improvement, the investigators are going to conduct a clinical trial using universal car-t(ucar-t) cells targeting cd19 for r/r b-all patients. after enrollment, patients will get a 3-5 days lymphodepletion therapy, then the ucar-t cells will be infused by vein. subjects will be followed for safety and efficacy up to 12 weeks. for those with a durable remission 12 weeks after infusion, the follow-up will last for at least 12 months for disease control.

Eligibility criteria:
inclusion criteria: 1. male or female, aged 2-75 years; 2. a definite diagnosis of relapsed/refractory b-all and a percentage of primitive/naive lymphocytes \>5% in bone marrow at baseline (flow cytometry); 3. cd19 expression was positive in bone marrow or peripheral blood tumor cells; 4. ecog score 0-2 points; 5. expected survival time ≥3 months; 6. adequate liver, kidney, heart and lung function; 7. patients who have recovered from acute toxic effects of prior chemotherapy should be excluded from the trial at least one week apart; 8. women of childbearing age have negative blood pregnancy test before the start of the trial, and agree to take effective contraceptive measures during the trial until the last follow-up; male subjects with partners of childbearing potential agree to take effective contraceptive measures during the trial until the last follow-up; 9. voluntarily sign the informed consent. exclusion criteria: 1. presence of other concurrent active malignancy; 2. people with severe mental disorders; 3. a history of any of the following genetic disorders, such as fanconi anemia, schu-day syndrome, gerstmann syndrome, or any other known bone marrow failure syndrome; 4. acute gvhd of grade ii-iv or extensive chronic gvhd; 5. had grade iii-iv heart failure or myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, or other clinically prominent heart disease within one year prior to enrollment; 6. the presence of any indwelling catheter or drainage (e.g., percutaneous nephrostomy, indwelling catheter, bile drainage, or pleural/peritoneal/pericardial catheter), except for patients who are permitted to use dedicated central venous catheters; 7. a history or disease of the central nervous system(cns), such as seizure disease, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involving the cns; 8. human immunodeficiency virus (hiv) seropositivity; hepatitis b surface antigen positive or hepatitis b core antibody positive, and hbv-dna positive; patients with hepatitis c (hcv-rna quantitative test results positive); or the presence of other serious active viral or bacterial infections or uncontrolled systemic fungal infections; 9. patients with severe history of allergy or allergic constitution; 10. a history of autoimmune diseases (e.g., crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) leading to end-organ damage or requiring systemic immunosuppressive/systemic disease modulating drugs within the past 2 years; 11. had or is suffering from interstitial lung disease (e.g., pneumonia, pulmonary fibrosis); 12. had undergone other clinical trials in the 4 weeks prior to participating in this trial; 13. poor compliance due to physiological, family, social, geographical and other factors, unable to cooperate with the study protocol and follow-up plan; 14. for patients contraindicated with cyclophosphamide and fludarabine chemotherapy; 15. subjects requiring systemic corticosteroid therapy (prednisone ≥5mg/ day or equivalent dose of another corticosteroid) or other immunosuppressive agents within 1 month after ucar-t cell reinfusion, except for adverse events; 16. receiving donor lymphocyte infusion within 6 weeks before enrollment; 17. pregnant and lactating women; 18. any other condition that the investigator deemed inappropriate for inclusion.

Keywords: universal car-t(ucar-t) cd19