Human CD19 Targeted T Cells Injection(CD19 CAR-T) Therapy for Relapsed and Refractory CD19-positive Lymphoma.

Phase 1

• Conditions: Follicular Lymphoma; CD19-positive; Diffuse Large B-cell Lymphoma
• Interventions: Drug: Human CD19 targeted T Cells Injection

• Registration Number: NCT03720457
• Lead Sponsor: Hrain Biotechnology Co., Ltd.

Brief Summary

To evaluate the safety and tolerance of human CD19 targeted T Cells injection for the treatment of relapsed and refractory CD19-positive diffuse large B-cell lymphoma and follicular lymphoma. Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19 CAR+ T cells.

Detailed Description

Participants with relapsed/refractory CD19-positive Diffuse Large B-cell Lymphoma and Follicular Lymphoma can participate if all eligibility criteria are met.Tests required to determine eligibility include disease assessments, a physical exam, Electrocardiograph, CT/MRI , and blood draws.Participants receive chemotherapy prior to the infusion of CD19 CAR+ T cells. After the infusion, participants will be followed for side effects and effect of CD19 CAR+ T cells. Study procedures may be performed while hospitalized.

Study Timeline

• Study First Submitted: 2018-10-24
• Study First Submitted QC: 2018-10-24
• Study First Posted: 2018-10-25
• Study Start: 2018-11-13
• Status Verified: 2021-08
• Last Update Submitted: 2021-08-29
• Last Update Posted: 2021-08-31
• Primary Completion: 2021-10
• Study Completion: 2023-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

Male or female subjects with CD19+ B cell lymphomas who have a limited prognosis (several months to <2 year survival) with currently available therapies will be enrolled.

1. 18 to 70 Years Old, Male and female;

2. Expected survival > 12 weeks;

3. Clinical performance status of ECOG score 0-1;

4. Pathology demonstrated that CD19-positive B-cell non-Hodgkin's lymphoma and who meet one of the following conditions:

   1. Relapsed and refractory CD19-positive Diffuse large B-cell lymphoma and Follicular lymphoma: patients previously received at least first-line and second- line treatment and fail to achieve CR;
   2. Disease recurrence after stem cell transplantation, and at least 1 years after stem cell transplantation.

5. It can establish the venous access required for collection, satisfying hemoglobin ≥ 70 g / L, neutrophils ≥ 1.0 × 10 ^ 9 / L, platelets ≥ 50 × 10 ^ 9 / L. Mononuclear cell collection can be determined by the investigators;

6. At least 1 measurable tumor foci according to the 2014 Lugano treatment response criteria;

7. Liver, kidney and cardiopulmonary functions meet the following requirements:

   1. Serum creatinine ≤ 1.5 × ULN;
   2. Left ventricular ejection fraction >50%, no pericardial effusion and no pleural effusion (ECHO examination);
   3. Baseline oxygen saturation > 92%;
   4. Total bilirubin ≤ 1.5 × ULN;
   5. ALT and AST ≤ 3 × ULN.

8. Able to understand and sign the Informed Consent Document.

Exclusion Criteria

1. In the first 5 years before screening, there are malignant tumors other than diffuse large B-cell lymphoma and follicular lymphoma, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery，and catheter carcinoma in situ after radical surgery;
2. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood HBV DNA titer higher than the upper limit of detection; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency Viral (HIV) antibody positive; Positive syphilis test;
3. Any unstable systemic disease including, but not limited to, active infection (except for local infection), unstable angina pectoris, cerebrovascular accident or transient cerebral ischemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ III), severe arrhythmia , liver, kidney or metabolic disease requiring medication;
4. Any other diseases could affect the outcome of this trial;
5. Any affairs could affect the safety of the subjects or outcome of this trial;
6. Pregnant or lactating women, or planned pregnancy during treatment or within 1 year after treatment, or a male subject whose partner plans pregnancy within 1 year of their cell transfusion;
7. Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment;
8. Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell transfusion;
9. Received CAR-T treatment or other gene therapies before enrollment;
10. Patients with symptoms of central nervous system or brain metastasis or have received treatment for central nervous system or brain metastasis (radiotherapy, surgery or other treatment) within 3 months before enrollment;
11. Subject suffering disease affects the understanding of informed consent or comply with study protocol;
12. The investigators consider other conditions unsuitable for enrollment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Human CD19 targeted T Cells Injection	Human CD19 targeted T Cells Injection	-

Primary Outcome Measures

Name	Time	Method
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 5.0	2 years post infusion

Secondary Outcome Measures

Name	Time	Method
Duration of CAR-positive T cells in circulation	2 years post infusion
Total number of CAR-positive T cells infiltrated into lymphoma tissue	2 years post infusion
Overall Survival after administration	90 days post infusion
Duration of Response after administration	90 days post infusion
Overall remission rate including complete response and Partial response defined by the standard response criteria for malignant lymphoma.	90 days post infusion
Progress Free Survival after administration	90 days post infusion
The immunogenicity of Human CD19 targeted T Cells Injection. (HAMA detection of human anti-mouse antibody)	2 years post infusion

Trial Locations

Locations (3)

Fudan University Zhongshan Hospital; 🇨🇳 Shanghai, Shanghai, China

The Second Affiliated Hospital of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China

The First Affilicated Hospital of Wenzhou Medical University; 🇨🇳 Wenzhou, Zhejiang, China