A Phase Ⅱ Clinical Study Evaluating the Efficacy and Safety of Human CD19 Targeted T Cells Injection (CD19 CAR-T) Therapy for Relapsed and Refractory B-cell Non-Hodgkin's Lymphoma

Hrain Biotechnology Co., Ltd.1 site in 1 country100 target enrollmentAugust 9, 2021

ConditionsB-cell Non-Hodgkin's Lymphoma

InterventionsHuman CD19Targeted T Cells Injection

DrugsHuman CD19Targeted T Cells Injection

Overview

Phase: Phase 2
Intervention: Human CD19Targeted T Cells Injection
Conditions: B-cell Non-Hodgkin's Lymphoma
Sponsor: Hrain Biotechnology Co., Ltd.
Enrollment: 100
Locations: 1
Primary Endpoint: Overall response rate (ORR) at 3 months post infusion
Status: Recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A Phase Ⅱ Clinical Study Evaluating the Efficacy and Safety of Human CD19 Targeted T Cells Injection (CD19 CAR-T) Therapy for R/R B-NHL.

Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19 CAR+ T cells.

Detailed Description

Subjects with relapsed and refractory B-cell non-Hodgkin's lymphoma would be selected if subjects meet all criteria evaluated by physical exams, blood tests, electrocardiograph, computedtomography （CT）/magnetic resonance Imaging(MRI)/positron emission tomography（PET）, tumor assessments, etc. Subjects would be hospitalized to receive the infusion of CD19 CAR+ T cells after lymphodepleting regimen, with the observation and evaluation of efficacy and safety.

Registry

clinicaltrials.gov

Start Date

August 9, 2021

End Date

August 9, 2026

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Hrain Biotechnology Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects with relapsed/refractory B-cell non-Hodgkin's lymphoma
•Age≥18 years old，gender is not limited;
•Expected survival \> 12 weeks;
•ECOG score 0-2;
•B-cell non-Hodgkin's lymphoma confirmed by cytology or histopathology according to the 2016 World Health Organization (WHO) classification and diagnostic criteria, including: diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed filter Alveolar lymphoma (TFL) and high-grade B-cell lymphoma (HGBCL);
•Pathology demonstrated that B-cell non-Hodgkin's lymphoma and who meet one of the following conditions:
•Relapsed and refractory B-cell non-Hodgkin's lymphoma, after standard first-line treatment and at least 2 courses of second-line treatment without remission and relapse (the previous use of CD20-targeted drugs and anthracyclines were needed);
•Relapse of B-cell non-Hodgkin lymphoma after stem cell transplantation, regardless of previous treatments.
•The venous access required for collection can be established and leukepheresis can be carried according to the judgement of investigators, satisfying hemoglobin≥80g/L, neutrophils ≥1.0×10\^9/L, platelets ≥75×10\^9 / L;
•According to the Lugano 2014 criteria, there should be at least one measurable tumor lesion;

Exclusion Criteria

•Any one of the following conditions cannot be selected as a subject：
•Malignant tumors other than diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (TFL), and high-grade B-cell lymphoma (HGBCL) within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, ductal carcinoma in situ after radical resection and thyroid cancer after radical resection ;
•Subjects with positive Hepatitis B surface antigen(HBsAg) or Hepatitis B core antibody (HBcAb) and positive peripheral blood hepatitis B virus (HBV) DNA titers (higher than the upper limit of the normal range of the investigative site); Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; Human Immunodeficiency Viral (HIV) antibody positive; syphilis positive;
•Any uncontrolled systemic diseases, including but not limited to active infection (except for localized infection), uncontrolled angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease;
•Any other uncontrolled active disease that precludes participation in the trial;
•Any circumstances that the investigator believes will compromise the safety of the subject or interfere with the purpose of the study;
•Pregnant or lactating woman, or planned pregnancy during treatment or within 1 year after treatment, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion;
•Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment (except uncomplicated urinary tract infection or upper respiratory tract infection);
•Subjects who were receiving systemic steroid treatment within 14 days before enrollment and who were judged by the investigator to require long-term use of systemic steroid therapy during treatment (except inhalation or topical use); or subjects who received any systemic anti-tumor therapy ( except for local anti-tumor therapy) ;
•Subjects who have received CAR-T treatment or other gene-modified cell therapy before enrollment;

Arms & Interventions

Human CD19 Targeted T Cells Injection

Single administration：2.0×10\^6 CAR+T/kg

Intervention: Human CD19Targeted T Cells Injection

Outcomes

Primary Outcomes

Overall response rate (ORR) at 3 months post infusion

Time Frame: 3 months post infusion

ORR is defined as proportion of subjects who achieved Partial remission(PR) or better at 3 months (D90±7) post infusion as assessed by an independent review committee (IRC) based on Lugano 2014 criteria.

Secondary Outcomes

Overall Survival (OS) after administration(2 years post infusion)
Disease control rate (DCR)(2 years post infusion)
Pharmacodynamic (PD) parameters(2 years post infusion)
Safety evaluation(2 years post infusion)
Pharmacokinetics(PK) parameters: 28-day Area under the curve of the CAR level in blood(AUC0-28)(2 years post infusion)
Pharmacokinetics(PK) parameters: Time to peak CAR level in blood (Tmax)(2 years post infusion)
Duration of remission (DOR) after administration(2 years post infusion)
Progression-free Survival (PFS) after administration(2 years post infusion)
Pharmacokinetic (PK) parameters: Maximum CAR level inperipheral blood(2 years post infusion)