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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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An Open Label, Single-site, Dose-escalation Study Aiming to Evaluate the Efficacy and Safety of Anti-CD19 CAR-T Manufactured by OlyCAR Platform(OlyCAR-019) in the Treatment of Relapsed/ Refractory(r/r) B-Cell Malignancies

Conditions
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B-Cell Leukemia, B-Cell Lymphoma, B-cell Tumors

Intervention / Treatment
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* Biological: Anti-CD19 Autologous CAR-T Cell Infusion


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: A definite diagnosis of relapsed/refractory B-cell malignancies; Male or female, aged 2-75 years; Confirmed detectable disease； Expected survival time >12 weeks; Eastern cooperative oncology group (ECOG) score is 0-2; Adequate liver , kidney and cardiopulmonary function; 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; Willingness to complete the informed consent process and to comply with study procedures and visit schedule. Key Exclusion Criteria: Presence of other concurrent active malignancy; People with severe mental disorders; 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; Acute GVHD of grade II-IV or extensive chronic GVHD; 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; 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; 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; 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); Had undergone other clinical trials in the 4 weeks prior to participating in this trial; Poor compliance due to physiological, family, social, geographical and other factors, unable to cooperate with the study protocol and follow-up plan; For patients contraindicated with cyclophosphamide and fludarabine chemotherapy; 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; Receiving donor lymphocyte infusion within 6 weeks before enrollment; Pregnant and lactating women; Subjects with any other condition which the investigator considers unsuitable for inclusion in the study.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients will receive one of the three doses of 0.5-2*10^6/kg, 3-4*10^6/kg, 5-6*10^6/kg.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OlyCAR-019 Cell Infusion<br>OlyCAR-019 cell infusion will be administered by vein after short-time manufacture. | Biological: Anti-CD19 Autologous CAR-T Cell Infusion<br>* Autologous T cells modified with anti-CD19 ScFv expression and manufactured by OlyCAR platform<br>* Other names: OlyCAR-019;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events(AE) after infusion | The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included. | Up to 12 months after infusion | 
| MTD | MTD will be determined based on DLTs observed during the first 28 days of study treatment. | Up to 28 days after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall Response Rate (ORR) is defined as the proportion of subjects achieving complete remission(CR) and partial response(PR). | Up to 3 months after infusion | 
| Progression-free survival(PFS) | Progression-free survival(PFS) refers to the time from cell infusion to the first assessment of tumor progression or death from any cause. | Up to 3 months after infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B Cell, CAR-T, CD19, Leukemia, Lymphoma