CD19 CAR-T Expressing IL-7 and CCL19 Combined With Anti-PD1 in RR-DLBCL

Study Overview
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Brief Summary
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The goal of this clinical trial is to test CD19-7×19 CAR-T cells combined with Tislelizumab in refractory and relapsed diffuse large B lymphoma. The main question[s] it aims to answer are: question 1：What is the safety of CD19-7×19 CAR-T cells combined with Tislelizumab in the treatment of relapsed or refractory diffuse large B-cell lymphoma. question 2：What is the efficacy of CD19-7×19 CAR-T cells combined with Tislelizumab in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Participants will be asked to receive clinical evaluation before CAR-T, including physical examination, blood routine test, biochemical test, imaging test, etc.Peripheral blood lymphocytes will be collected for preparation of CAR-T cells after enrollment. Pretreatment chemotherapy with fludarabine and cyclophosphamide will be used before CAR-T infusion. On the 31st day after CAR-T infusion, Tislelizumab 200mg was given once every 21 days for 6 cycles. Participants will be required to report concomitant medication and adverse events, and their disease was evaluated throughout the study.

Official Title
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Phase Ib Clinical Study of CD19 CAR-T Expressing IL-7 and CCL19 Combined With Tislelizumab in the Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Combination Product: CD19-7×19 CAR-T combined with Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18, upper limit 75, male or female; ECOG score 0-3; Histologically confirmed diffuse large B-cell lymphoma (DLBCL) [diagnostic criteria according to WHO 2008]; CD19 positive (immunohistochemistry or flow cytometry). DLBCL refractory or relapse is defined as: complete remission is not achieved after 2-line treatment; let What disease progress occurs during treatment, or the disease stability time is equal to or less than 6 months; Or autologous hematopoietic stem Disease progression or recurrence within 12 months after cell transplantation; Previous treatment for patients with diffuse large B cell lymphoma must include rituximab (CD20 monoclonal antibody) and anthracyclines; At least one measurable lesion is required, and any lymph node lesion with a length greater than 1.5cm or extranodal lesion is required If any length diameter is greater than 1.0 cm, the lesions on PET-CT scan have uptake (SUV is larger than liver blood pool); Absolute value of peripheral blood neutrophils ≥ 1000/ μ l. Platelets ≥ 45000/ μ l Heart, liver and kidney functions: creatinine < 1.5mg/dL; ALT/AST Less than 2.5 times of normal upper limit; Total bilirubin < 1.5mg/dL; Cardiac ejection fraction (EF) ≥ 50%; Have sufficient understanding and voluntarily sign the informed consent form; People with fertility must be willing to use contraceptive methods; According to the judgment of the researcher, the expected survival period is at least 4 months; Willing to follow the visit schedule, administration plan, laboratory inspection and other test steps. Exclusion Criteria: Have a history of other tumors; Autologous hematopoietic stem cell transplantation was performed within 6 weeks; Any target CAR-T treatment was performed within 3 months before this CAR-T treatment; Previously used any commercially available PD-1 monoclonal antibody; Cytotoxic drugs, glucocorticoids and other targeted drugs were received within 2 weeks before cell collection; Active autoimmune diseases; Uncontrollable active bacterial and fungal infections; HIV infection and syphilis infection; Active hepatitis B or hepatitis C: hepatitis B: HBV-DNA ≥ 1000 IU/mL; Hepatitis C: HCV RNA is positive and liver function is abnormal. Known central nervous system lymphoma.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAR-T combined with anti-PD1 treatment group<br>CD19-7×19 CAR-T combined with Tislelizumab | Combination Product: CD19-7×19 CAR-T combined with Tislelizumab<br>* Participants will receive 2×106/Kg CD19-7×19 CAR-T cells infusion and Tislelizumab 200mg every 21 days for 6 cycle on the 31st day after CAR-T infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events profile | Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 will be tabulated. | Measured from start of treatment until 28 days after last dose. | 
| Objective Response Rate | Proportion of CR and PR subjects will be assessed at 3 months post-infusion. | up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress free survival time | To measure the duration of response over a follow-up period of 24 months. | up to 24 months | 
| Overall survival | OS will be assessed from the first chimeric antigen receptor T cells (CAR-T) given to death or last follow-up. | up to 24 months |