A Study of Novel Anti-CD19 CAR-T in Patients With r/r B-Cell Malignancies

Overview

It is a single-center, open-labeled, single-arm, non-randomized, investigator-initiated trial aiming to evaluate the efficacy and safety of anti-CD19 CAR-T manufactured by OlyCAR platform (OlyCAR-019) for CD19+ refractory/relapsed B-Cell malignancies.

Description

OlyCAR is a novel CAR-T manufacturing system which allows to generate clinical-use CAR-T cells in short time. This study is going to evaluate the feasibility of CAR-T manufactured by OlyCAR platform in the treatment of B-Cell malignancies. The OlyCAR-019 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

Key Inclusion Criteria:

1. A definite diagnosis of relapsed/refractory B-cell malignancies;
2. Male or female, aged 2-75 years;
3. Confirmed detectable disease；
4. Expected survival time >12 weeks;
5. Eastern cooperative oncology group (ECOG) score is 0-2;
6. Adequate liver , kidney and cardiopulmonary function;
7. 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;
8. Willingness to complete the informed consent process and to comply with study procedures and visit schedule.

Key Exclusion Criteria:

1. Presence of other concurrent active malignancy; People with severe mental disorders;
2. 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;
3. Acute GVHD of grade II-IV or extensive chronic GVHD;
4. 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;
5. 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;
6. 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; Patients with severe history of allergy or allergic constitution;
7. 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; Had or is suffering from interstitial lung disease (e.g., pneumonia, pulmonary fibrosis);
8. Had undergone other clinical trials in the 4 weeks prior to participating in this trial;
9. Poor compliance due to physiological, family, social, geographical and other factors, unable to cooperate with the study protocol and follow-up plan;
10. For patients contraindicated with cyclophosphamide and fludarabine chemotherapy;
11. 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;
12. Receiving donor lymphocyte infusion within 6 weeks before enrollment;
13. Pregnant and lactating women;
14. Subjects with any other condition which the investigator considers unsuitable for inclusion in the study.