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

NCT ID: NCT03720457

Last Updated: 2021-08-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-13
• Study Completion Date: 2023-10-31

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.

Conditions

CD19-positive; Diffuse Large B-cell Lymphoma; Follicular Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Human CD19 targeted T Cells Injection

Group Type: EXPERIMENTAL

Human CD19 targeted T Cells Injection

Intervention Type: DRUG

Autologous genetically modified anti-CD19 CAR transduced T cells

Interventions

Human CD19 targeted T Cells Injection

Autologous genetically modified anti-CD19 CAR transduced T cells

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: collaborator

Hrain Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status: RECRUITING

Fudan University Zhongshan Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

The First Affilicated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hongliang Fang, Dr.

Role: CONTACT

fanghongliang@dashengbio.com

021-58552006

Facility Contacts

Qingming Wang, M.D.

Role: primary

wqming222@163.com

0791-86300483

Peng Liu, Professor

Role: primary

Liu.peng@zs-hospital.sh.cn

021-60267405

Songfu Jiang

Role: primary

jiangsongfu@189.cn

0577-55578023

References

Wang H, Tsao ST, Gu M, Fu C, He F, Li X, Zhang M, Li N, Hu HM. A simple and effective method to purify and activate T cells for successful generation of chimeric antigen receptor T (CAR-T) cells from patients with high monocyte count. J Transl Med. 2022 Dec 19;20(1):608. doi: 10.1186/s12967-022-03833-6.

Reference Type: DERIVED

PMID: 36536403 (View on PubMed)

Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

Reference Type: DERIVED

PMID: 34515338 (View on PubMed)

Other Identifiers

CTR20181354

Identifier Type: OTHER

Identifier Source: secondary_id

HRAIN01-NHL01

Identifier Type: -

Identifier Source: org_study_id