A Single-arm, Open-label, Dose Escalation Study to Explore Safety, Efficacy and Pharmacokinetics of Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific CAR-T Cells in Adult Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma

Fujian Medical University1 site in 1 country18 target enrollmentDecember 2019

ConditionsRelapsed or Refractory DLBCL Patients With Either CD19 or CD20 Positive

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Relapsed or Refractory DLBCL Patients With Either CD19 or CD20 Positive
Sponsor: Fujian Medical University
Enrollment: 18
Locations: 1
Primary Endpoint: The types and Incidence of adverse events
Status: Recruiting
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single-arm, open-label, dose escalation, phase I study, aiming to evaluate the safety and efficacy of Autologous Humanized Anti-CD19 and Anti-CD20 Dual Specific Chimeric Antigen Receptor (CAR) T-cells in patient with relapsed or refractory diffuse B cell lymphoma.

Detailed Description

CD19 CAR-T cell therapy has made breakthroughs in the treatment of B cell lymphoma and leukemia, but 30% of patients still have antigen escape, which may be related to variants in tumor cells and the expansion of CD19-negative tumor cells after treatment with CD19 CAR-T cells. CD19/CD20 bispecific CAR-T cell targeting multiple antigens can attack tumor cells while overcoming tumor antigen escape caused by a single target, maximizing efficacy and duration of treatment, and can also solve the problem of uneven distribution or low expression of single target on the tumor surface.

Registry

clinicaltrials.gov

Start Date

December 2019

End Date

December 2024

Last Updated

6 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Fujian Medical University

Responsible Party

Principal Investigator

Jianda Hu

Director of the department of Hematology

Fujian Medical University

Eligibility Criteria

Inclusion Criteria

•The subject or her/his legally guardian(s) must sign the informed consent form approved by the Institutional Ethics Committee (IEC) prior to any screening procedures;
•Subjects aged 18 years or older with relapsed or refractory DLBCL (primary mediastinal large B-cell lymphoma and transformed follicular lymphoma included), of which refractory is defined as:
•Have no response to the recent treatment including:
•The best response to the treatment regimen is progressive disease (PD) ,or
•stable disease (SD) which maintained less than 6 months after the last treatment, or
•not suitable for autologous hematopoietic stem cell transplantation (ASCT), or ASCT refractory, including:
•progressive disease after ASCT or relapse within 12 months (relapse must be confirmed by biopsy), or
•If remedial treatment is given after ASCT, the subject must have no response or relapse after the last treatment.
•Subjects who have previously received ≥2 lines treatment, and at least including:
•Anti-CD20 monoclonal antibody(rituximab), unless the CD20 negative;

Exclusion Criteria

•Prior treatment with any cell therapy before signing the informed consent form, including CAR-T therapy;
•Subjects with detectable cerebrospinal fluid malignant cells or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma;
•Subjects with testicular invasion, including those who have had testicular resection;
•Subjects with current or previous history of central nervous system disease, such as seizures, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system;
•Subjects who have previously received allogeneic hematopoietic stem cell transplantation (HSCT); or suitable and consenting to Autologous hematopoietic stem cell transplantation (ASCT);
•Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of A-02 infusion;
•Patients on oral anticoagulation therapy within 1 week of A-02 infusion;
•Prior radiation therapy within 2 weeks of A-02 infusion;
•Investigational medicinal product within the last 30 days prior to sign the informed consent form;
•Subjects with active hepatitis B（defined as hepatitis B surface antigen positive, or hepatitis B core antibody positive with hepatitis B virus DNA detection value \> 1000 copies/ml）or hepatitis C (HCV RNA positive)