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

Follicular Lymphoma Clinical Trial

Official title:

A Phase I Clinical Trial of Human CD19 Targeted T Cells Injection for Subjects With Relapsed and Refractory CD19-positive Diffuse Large B-cell Lymphoma and Follicular Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03720457
• Other study ID #: HRAIN01-NHL01
• Secondary ID: CTR20181354
• Status: Recruiting
• Phase: Phase 1
• Start date: November 13, 2018
• Est. completion date: October 2023

Study information

• Verified date: August 2021
• Source: Hrain Biotechnology Co., Ltd.
• Contact: Hongliang Fang, Dr.
• Phone: 021-58552006
• Email: fanghongliang[@]dashengbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: October 2023
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• CD19-positive
• Diffuse Large B-cell Lymphoma
• Follicular Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Human CD19 targeted T Cells Injection
Autologous genetically modified anti-CD19 CAR transduced T cells

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Fudan University Zhongshan Hospital	Shanghai	Shanghai
China	The First Affilicated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Hrain Biotechnology Co., Ltd.	Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 5.0		2 years post infusion
Secondary	Duration of CAR-positive T cells in circulation		2 years post infusion
Secondary	Total number of CAR-positive T cells infiltrated into lymphoma tissue		2 years post infusion
Secondary	Overall remission rate including complete response and Partial response defined by the standard response criteria for malignant lymphoma.		90 days post infusion
Secondary	Duration of Response after administration		90 days post infusion
Secondary	Progress Free Survival after administration		90 days post infusion
Secondary	Overall Survival after administration		90 days post infusion
Secondary	The immunogenicity of Human CD19 targeted T Cells Injection. (HAMA detection of human anti-mouse antibody)		2 years post infusion