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

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

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.

Study Overview

• Status: Recruiting
• Conditions: B-Cell Leukemia; B-Cell Lymphoma; B-cell Tumors
• Intervention / Treatment: Biological: Anti-CD19 Autologous CAR-T Cell Infusion

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sanbin Wang, Professor; Phone Number: +86 13187424131; Email: Sanbin1011@163.com
• Study Contact Backup: Name: Shiqi Li, MD; Phone Number: 15398671578; Email: Lystch@qq.com

Study Locations

• China
  • Yunnan
    • Kunming, Yunnan, China, 650100
      • Recruiting
      • 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
      • Contact: Lihua Zhang; Phone Number: +0871 64774204; Email: zhanglihua95@126.com
      • Principal Investigator: Sanbin Wang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
• Investigators: Principal Investigator: Sanbin Wang, Professor, 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: June 27, 2023
• First Submitted That Met QC Criteria: June 27, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 9, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: CAR-T; Lymphoma; Leukemia; CD19; B Cell
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia, Lymphoid; Leukemia; Chronic Disease; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, B-Cell
• Other Study ID Numbers: KM-PBC920

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No