A Study of CD19/22 CART Cells Combined With PD-1 Inhibitor in Relapsed/Refractory B-cell Lymphoma

Study Overview
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Brief Summary
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This is a single center, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of CD19/22 CART cells combined with PD-1 Inhibitor in relapsed/refractory B Cell Lymphoma.

Detailed Description
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Though response rates have greatly improved with the development of Chimeric antigen receptor T cells (CART) therapy in refractory/relapsed B cell non-Hodgkin's lymphoma (R/R B-NHL), the response can't usually last long and relapse occurs in a large proportion of patients who receive CART cells infusion. The main reasons of relapse might be tumor antigen loss and a lack of CART cell persistence. Currently, preclinical studies have shown that there is a synergistic effect between CAR-T cell therapy and anti-PD1 pathway, and it did have efficacy in clinic. In parallel, the combined use of CART-19 and CART-22 cells has a better potential to reduce antigen escape and increase anti-tumor activity. Therefore, the combination of CD19/22 CART and PD-1 inhibitor is one of the ways to improve the therapeutic effect of CART cells. This study was conducted to explore the efficacy and safety of CD19/22 CART cells in R/R B-NHL.

Official Title
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A Study Evaluated Efficacy and Safety of CD19/22 Chimeric Antigen Receptor T Cells Combined With PD-1 Inhibitor in Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

Conditions
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Relapsed Non Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma

Intervention / Treatment
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* Biological: CD19/22 CART
* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: R/R B-NHL with measurable (≧1.5cm) lesions confirmed by pathological immunohistochemistry or flow cytometry ( meeting any of the following conditions): A.The lesion shrinkage <50% or disease progression after 4 courses of standard first-line treatment or 2 courses of two-line treatment (primary refractory disease) B. Progress disease as the best response after hematopoietic stem cell transplantation C.Progress disease or stable disease as the best response to most recent therapy regimen Age ≥ 18 years The Eastern Cooperative Oncoloy Group (ECOG) physical condition score ≤ 2 points The main organ functions need to meet the following conditions: A.Left ventricular ejection fraction ≥50% B.Creatinine ≤132umol/l or creatinine clearance ≥60 ml/min C.ALT and AST≤2 upper limitation of normal D.SpO2 > 90% Results of pregnant test should be negative, and agree to conception control during treatment and 1 year after CAR-T infusion Expected survival exceeds 3 months Written informed consent could be acquired Exclusion Criteria: Immunosuppressant medications or steroids was used within 2 weeks before cell collection, or need to use steroids or immunosuppressant medications more than two years Uncontrolled bacteria, fungi, viruses, mycoplasma or other types of infection Active hepatitis B or hepatitis C infection HIV infection Severe acute or chronic graft-versus-host disease (GVHD) Participated in any other drug research clinical trials within 30 days before enrollment Prior CART cells therapy within 3 months before enrollment Prior allogeneic hematopoietic stem cell transplantation within 6 months before enrollment Have contraindications to the PD-1 inhibitors Uncontrolled other tumor Women in pregnancy,lactation or planning to become pregnant The researcher considers inappropriate to participate in this research

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: CD19/22 CART cells combined with PD-1 inhibitors<br>Patients will receive PD-1 inhibitor on the first day after CART cell infusion | Biological: CD19/22 CART<br>* CD19/22 CART cells are administrated in a 3-day split-dose regimen at dose of 0.5- 2×10*107 CART cells per kilogram of body weight.<br>Drug: Tislelizumab<br>* Patients will receive Tislelizumab 200mg/dose every 3 weeks.<br>* Other names: PD-1 inhibitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Number of patients who achieved response (complete response and partial response ) after treatment of CD19/22 CART combined with PD-1 inhibitor. Response will be assessed using the Lugano criteria. | 1 year | 
| Progression-free survival(PFS) | PFS will be assessed from the first CART cell infusion to progression,death or last follow-up. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete relapse rate(CR) | Number of patients who achieved complete response after treatment by CD19/22 CART combined with PD-1 inhibitor. | 1 year | 
| Duration of overall response (DOR) | Duration of overall response will be assessed from the first CAR-T cell infusion to progression,death or last follow-up. | 1 year | 
| Overall survival(OS) | OS will be assessed from the first CART cell infusion to death or last follow-up. | 1 year | 
| Incidence of treatment-related adverse events | The incidence rate of adverse events from the first day of preconditioning chemotherapy to 1 year after CART cells infusion | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chimeric antigen receptor T cells, Relapsed or refractory B cells non-Hodgkin's lymphoma, PD-1 inhibitor