Clinical Trial of SL1904B CAR-T Cells for Relapsed or Refractory Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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This is a study of patients with relapsed or refractory non-Hodgkin's lymphoma. To evaluate the safety and efficacy of SL1904B in patients with relapsed or refractory non-Hodgkin's lymphoma.

Detailed Description
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The CARs consist of an anti-CD19 single-chain variable fragment（scFv） that was derived from the FMC63 mouse hybridoma, a portion of the human CD137（4-1BB） molecule, and the intracellular component of the human CD3ζ molecule. Prior to CAR-T cell infusion, the patients will be subjected to preconditioning treatment. After CAR-T cell infusion, the patients will be evaluated for adverse reactions and efficacy. The Main research objectives: To evaluate the safety and efficacy of SL1904B in patients with recurrent or refractory non-Hodgkin's lymphoma The Secondary research objectives: To investigate the cytokinetic characteristics of SL1904B in patients with recurrent or refractory non-Hodgkin's lymphoma.

Official Title
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Clinical Trial of SL1904B CAR-T Cells for Relapsed or Refractory Non-Hodgkin Lymphoma

Conditions
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Non-hodgkin's Lymphoma

Intervention / Treatment
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* Biological: CD19 CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent form and be willing and able to comply with the visit, treatment regimen, laboratory examination and other requirements of the study as stipulated in the trial flow chart; The diagnosis of patients with relapsed or refractory non-hodgkin lymphoma; There should be at least one measurable tumor focus according to the RECIST version 1.1; ECOG Scores: 0 2; The expression of CD19 on the tumor cells was reported as positive by either immunohistochemistry or flow cytometry; Estimated survival time was longer than 3 months; main organ functions shall meet the following requirements including: serum creatinine ≤1.5 times the upper limit of normal value (ULN); ALT ULN 2.5 or less; AST ULN 2.5 or less; Total bilirubin ≤ 1.5ULN; Left ventricular ejection fraction (LVEF) ≥45%; Hemoglobin ≥90g/L; Platelet count ≥50×109/L; absolute Neutrophil count (ANC) ≥1.0×109/L; Blood oxygen saturation >92%； Peripheral blood mononuclear immune cells must be collected at least 2 weeks after the last radiotherapy or systemic treatment. Exclusion Criteria: Serious cardiac insufficiency； Has a history of severe pulmonary function damaging; With other tumors which is/are in advanced malignant and has/have systemic metastasis; Merging the metabolic diseases (except diabetes); Merging severe autoimmune diseases or immunodeficiency disease; Patients with active hepatitis B or hepatitis C virus infection; Patients with HIV infection or syphilis infection; Has a history of serious allergies on Biological products (including antibiotics); Participated in any other clinical drug trial for the last six months; Being pregnant and lactating or having pregnancy within 12 months; With other uncontrolled diseases and considered not suitable to participate by the researchers; Any situations that the researchers believe will increase the risks for the subject or affect the results of the study.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 70 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: SL1904B CAR-T<br>Patients will be treated with CD19 CAR-T cells | Biological: CD19 CAR-T<br>* Biological: CD19 CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis;<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence and severity of adverse events | To evaluate the possible adverse events occurred within first one month after SL1904B infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity | First month post CAR-T cells infusion | 
| Efficacy: Overall Remission Rate (ORR) | Overall Remission Rate (ORR) including partial remission and complete remission rate after infusion of SL1904B | 3 months post CAR-T cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy:duration of response (DOR) | duration of response (DOR) | 24 months post CAR-T cells infusion | 
| Efficacy: progression-free survival (PFS) | progression-free survival (PFS) time | 24 months post CAR-T cells infusion | 
| CAR-T proliferation | the copy number of CD19 CAR- T cells in the genomes of PBMC by qPCR method and percentage of CD19 CAR- T cells measured by flow cytometry method | 3 months post CAR-T cells infusion | 
| Cytokine release | Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method | First month post CAR-T cells infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NHL，CD19