CD19/22 Bi-specific CAR-T Cell Therapy

Study Overview
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Brief Summary
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The purpose of this study is to assess the feasibility, safety and efficacy of anti-CD19/22 bi-specific CAR-T cell therapy in patients with CD19 and/or CD22 positive B cell malignancies. Another goal of the study is to learn more about the safety and function of the anti-CD19/22 bi-specific CAR-T cells and their persistency in patients.

Detailed Description
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Patients with refractory and/or recurrent B cell malignancies have poor prognosis despite complex multimodal therapy. Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Further, more than 40% patients with progressive large B cell lymphoma (LBCL) experienced reduced or lost expression of CD19 on the tumor cells after CAR19 treatment; low surface CD19 density before treatment was associated with progressive disease. Therefore, novel curative approaches are needed. The investigation attempts to use genetically modified T cells to express a 4th generation lentiviral anti-CD19/22 bi-specific CAR (bi-4SCAR-CD19/22). The CAR molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, CD19 or CD22, which is expressed at high levels on tumor cells but not at significant levels on normal tissues. To overcome tumor escape of single target antigen and enhance in vivo CAR-T efficacy, a novel bi-specific CD19/22 CAR-T therapy regimen is developed to include booster and consolidation CAR-T applications to target highly-refractory B cell cancer. The aim is to evaluate safety and long term efficacy of the bi-CAR-T therapy strategy in CD19 and/or CD22 positive cancer patients.

Official Title
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CD19/22 Bi-specific CAR-T Cells Targeting B Cell Malignancies

Conditions
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B Cell Malignancies

Intervention / Treatment
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* Biological: bi-4SCAR CD19/22 T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age older than 6 months. malignant B cell surface expression of CD19 or CD22 molecules. the KPS score over 80 points, and survival time is more than 1 month. greater than Hgb 80 g/L.5. no contraindications to blood cell collection. Exclusion Criteria: accompanied with other active diseases and difficult to assess patient response. bacterial, fungal, or viral infection, unable to control. living with HIV.4. active HBV or HCV infection. 5. pregnant and nursing mothers. 6. under systemic steroid treatment within a week of the treatment. 7. prior failed CD19 and CD22 CAR-T treatment.

Ages Eligible for Study
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Minimum Age: 6 Months
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: bi-4SCAR-CD19/22 T Cell Therapy for CD19 and/or CD22 positive B cell malignancies<br> | Biological: bi-4SCAR CD19/22 T cells<br>* Infusion of bi-4SCAR CD19/22 T cells at 10^6 cells/kg body weight via IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of fourth generation bi-4SCARCD19/22 T cells in patients with B cell malignancies | Safety of fourth generation bi-4SCARCD19/22 T cells in patients with B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events standard to evaluate the level of adverse events | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti tumor activity of fourth generation bi-4SCARCD19/22 T cells in patients with relapsed or refractory B cell malignancies | scale of CAR copies and leukemic cell burden (for efficacy) | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR-T, B cell Malignancies, CD19, CD22