Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T for Refractory/Relapsed B Cell Lymphoma.

Study Overview
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Brief Summary
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It's a single arm, open label prospective study, in which the safety and efficacy of Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T therapy are evaluated in refractory/relapsed B cell lymphoma patients.

Official Title
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Interleukin-7 and Chemokine (C-C Motif) -Ligand 19-expressing CD19-CAR-T for Refractory/Relapsed B Cell Lymphoma

Conditions
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B Cell Lymphoma

Intervention / Treatment
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* Biological: Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age 18-75 years old, male or female; 2. ECOG 0-3, for patients with ECOG=4, if ECOG reach 0-3 after bridging treatment with ibrutinib, they are also considered to fit this criteria; 3. Histologically diagnosed as B cell non-Hodgkin's lymphoma (NHL)(according to WHO 2008 criteria), including DLBCL-NOS, primary mediastinal B cell lymphoma (PMBCL) mantel cell lymphoma (MCL), transformed follicular lymphoma (TFL) and other transformed B cell NHL; 4. CD19 positive (by immuno-histology or flowcytometry) [for DLBCL/PMBCL/TFL patients, negative CD19 immuno-histology results also acceptable]; 5. Definition of relapsed and refractory disease: 1) refractory DLBCL should fit one of the following: ①complete remission NOT achieved after 2nd line treatment; ②progression of disease during treatment; ③duration of stable disease <6 months; ④ disease progress or relapse within 12 months of autologous stem cell transplantation. 2) definition of refractory/relapsed disease for CLL and other indolent B cell NHL, should fit one of the following: ① failed or relapsed after 2nd therapy (Rituximab must be included) and being unable to accept ibrutinib treatment due to various reasons; ② non-responsive or intolerable to ibrutinib as 2nd line treatment; 3) refractory or relapsed MCL should fit one of the following: ① complete remission not achieved after 2nd line treatment; ② disease progression during treatment; ③duration of stable disease ≤6 months; ④disease progress or relapse within 12 months of autologous stem cell transplantation. 6. Previous treatment of aggressive B lymphomas must include Rituximab and anthracyclines; 7. Patients should have at least one measurable disease focus, with the longitudinal diameter ≥1.5cm, or any extra-nodal focus with the longitudinal diameter ≥1.0cm, with PET/CT positive results; 8. Blood routine test, absolute neutrophil count≥1000/ul、platelet count≥45000/ul； 9. Cardiac, hepatic and renal function: Creatinin <1.5 times of normal maximum；ALT/AST level <2.5 times of the maximum of normal range; total bilirubin<1.5 times of ULN；cardiac ejection fraction≥ 50%; 10. Patients should have the ability to fully understand contents of the written consent and be willing to sign the written consent; 11. Fertile patients should agree to take contraceptive measures during the process of this trial. Exclusion Criteria: 1. History of other malignant tumor; 2. History of autologous stem cell transplantation within 6 weeks prior to enrollment; 3. Received CAR-T therapy within 3 months prior to enrollment; 4. Received cytotoxic medicine or glucocorticoids or other targeted-therapy medicine (except for ibrutinib) within 2 weeks prior to T cell collection; 5. With active autoimmune disease; 6. With active infection; 7. With HIV infection, or uncontrolled HBV/HCV/syphilis infection; 8. With 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: Intervention group<br>In this group, patients will be treated with Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T, and the safety and efficacy will be evaluated. | Biological: Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T cells<br>* patient's T cells were seperated and engineered into Interleukin-7 and Chemokine (C-C Motif) Ligand 19-expressing CD19-CAR-T cells, and retransfused into the patient for treatment of their B cell lymphoma.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission rate | complete remission rate after treated by CAR-T therapy | at the time point 3 months after CAR-T cell transfusion | 
| adverse events | any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure | from the date of the start of treatment to 24 months after last patient's enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free surviva | from date of inclusion to date of progression, relapse, or death from any cause | from the day of treatment to the date of first documented progression，up to 24 months after the last patient's enrollment | 
| overall survival | from the date of inclusion to date of death, irrespective of cause | from the day of treatment to the date of first documented progression，up to 24 months after the last patient's enrollment | 
| duration of the CAR-T cells in the patients | time from re-transfusion to date when the modified T cells become non-detectable. | from the date of re-transfusison to 24 months after last patient's enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interleukin 7, Chemokine (C-C Motif) Ligand 19, CAR-T