Safety and Efficacy of Sequential CD19 and CD22 Targeted CAR-T Therapy for Relapsed/Refractory B Cell Lymphoma

Study Overview
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Brief Summary
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This is a single arm study to evaluate the efficacy and safety of Sequential CD19 and CD22 targeted CAR-T cells therapy for patients with relapsed/refractory B Cell Lymphoma.

Detailed Description
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Although the CD19 targeted CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell Leukemia and Lymphoma. There are some patients who resisted anti-CD19 CAR-T cells or get CD19 negative relapse. To make further improvement, We launch such a clinical trial using sequential CD19 and CD22 targeted CAR-T cells for patients with relapsed and refractory B Cell Lymphoma to evaluate the efficacy and safety of sequential CD19 and CD22 targeted CAR-T cell therapy.

Official Title
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Phase 1/Phase 2 Study of Sequential Chimeric Antigen Receptor T Cell Targeting at CD19 and CD22 B-cell Antigens Treating Refractory or Relapsed B-cell Lymphoma Patients

Conditions
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Lymphoma, B-Cell

Intervention / Treatment
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* Biological: CD19 and CD22 targeted CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory B cell non-hodgkin lymphoma. KPS>60. Life expectancy>12 weeks. Gender unlimited, age from 3 years to 70 years. Evidence for cell membrane CD19 and/or CD22 expression; Patients who have failed at least one line of a standard treatment. No serious mental disorder. Patients must have adequate cardiac function(no cardiac disease, LVEF≥40% ), adequate pulmonary function as indicated by room air oxygen saturation of >94%, and adequate renal function(Cr≤133umol/L). No other serious diseases(autoimmune disease, immunodeficiency etc.). No other tumors. Patients volunteer to participate in the research. Patients with history of allogeneic stem cell transplantation are eligible if at least 100 days post-transplant, if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to trial Exclusion Criteria: Pregnancy and nursing females. Patients are allergic to cytokines. Uncontrolled active infection. Acute or chronic GVHD. Treated with T cell inhibitor. Patients who had used steroid hormones within one week. Patients who had used Rituximab within two weeks. HIV/HBV/HCV Infection. Other situations we think improper for the research.

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: arm 1<br>sequential CD19 and CD22 targeted CAR-T cells treat | Biological: CD19 and CD22 targeted CAR-T cells<br>* CAR-T cells were manufactured from peripheral blood mononuclear cells collected by leukapheresis and frozen for multiple uses. Before each CAR T-cell infusion (day 0), patients received lymphodepleting chemotherapy composing of Fludarabine (30 mg/m2/day) and Cyclophosphamide (300 mg/m2/day) on days -5 to -3. No bridging chemotherapy was given between enrollment and infusion. In sequential CAR-T clinical trials, CAR-T cells will be given.（anti-CD19 CAR-T first, then anti-CD22 CAR-T).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events that related to treatment | Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0). | 1 years | 
| Overall remission rate (ORR) | The ORR of Sequential CD19 and CD22 CAR-T treatment will be recorded and assessed according to the revised 2014 Lugano Criteria. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete response(CR) | The CR of Sequential CD19 and CD22 CAR-T treatment will be recorded and assessed according to the revised 2014 Lugano Criteria. | 24 months | 
| partial response(PR) | The PR of Sequential CD19 and CD22 CAR-T treatment will be recorded and assessed according to the revised 2014 Lugano Criteria. | 24 months | 
| stable disease(SD) | The SD of Sequential CD19 and CD22 CAR-T treatment will be recorded and assessed according to the revised 2014 Lugano Criteria. | 24 months | 
| progressive disease(PD) | The PD of Sequential CD19 and CD22 CAR-T treatment will be recorded and assessed according to the revised 2014 Lugano Criteria. | 24 months | 
| Duration of remission (DOR) | DOR will be assessed from the first assessment of CR/CRi to the first assessment of recurrence or progression of the disease or death from any cause. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR-T, Lymphoma