Anti-CD19/CD22 Bispecific CAR-T Cell Therapy for CD19-positive ALL

Study Overview
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Brief Summary
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The goal of this clinical trial is to study the feasibility and efficacy of anti-CD19/CD22 bispecific chimeric antigen receptors (CARs) T cell therapy for CD19-positive Acute Lymphoblastic Leukemia.

Detailed Description
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Primary Objectives 1. To determine the feasibility ad safety of anti-CD19/ CD22 CAR-T cells in treating patients with CD19-positive Acute Lymphoblastic Leukemia. Secondary Objectives To determine in vivo expression, dynamics and persistency of anti-CD19/CD22 CAR-T cells. To determine in vivo expression of CD19-positive B cells. To access the complete remission rate (ORR) in patients with ALL with 3 months after CD19/CD22 CAR-T cells infusion. To investigate the favorable CD19/CD22 CAR-T cells dose and dosage regimen for the Phase II Clinical Trial.

Official Title
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A Phase I Clinical Trial of T-Cells Targeting CD19 and CD22 for Subjects With CD19-positive Acute Lymphoblastic Leukemia

Conditions
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CD19-positive ALL

Intervention / Treatment
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* Biological: anti-CD19/CD22 CAR-T cells
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 13 Years to 70 Years, Male and female; Expected survival > 12 weeks; Clinical performance status of ECOG score 0-2; Histologically confirmed as CD19-positive lymphoma and who meet one of the following conditions: Patients received at least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment; Disease recurrence after stem cell transplantation. Accessible to intravenous injection, and no white blood cell collection contraindications Patients who meet the following conditions: Creatinine < 2.5 mmol/l; Cardiac ejection fraction>50%, no pericardial effusion and no pleural effusion (ECHO examination); Baseline oxygen saturation>92%; Total bilirubin≤1.5xULN; ALT/AST≤2.5x normal. Able to understand and sign the Informed Consent Document. Exclusion Criteria: Accompanied by other malignant tumor Active hepatitis B, hepatitis C, syphilis, HIV infection Suffering severe cardiovascular or respiratory disease Any other diseases could affect the outcome of this trial Any affairs could affect the safety of the subjects or outcome of this trial Pregnant or lactating women, or patients who plan to be pregnancy during or after treatment Occurrence of infection uncontrolled or requiring systemic treatment 14 days prior to assignment Patients who are accounted by researchers to be not appropriate for this test Received CAR-T treatment or other gene therapies before assignment Patients with symptoms of central nervous system Subject suffering disease affects the understanding of informed consent or comply with study protocol.

Ages Eligible for Study
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Minimum Age: 13 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: anti-CD19/CD22 CAR-T cells<br>Administration with anti-CD19/CD22 CAR-T cells in the CD19-positive ALL patients | Biological: anti-CD19/CD22 CAR-T cells<br>* Retroviral vector-transduced autologous T cells to express anti-CD19 and anti-CD22 CARs<br>Drug: Fludarabine<br>* 30mg/m2/d<br>Drug: Cyclophosphamide<br>* 500mg/m2/d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 | Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm | Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm | 8 weeks | 
| Duration of CAR-positive T cells in circulation | Duration of CAR-positive T cells in circulation | 6 months | 
| Total number of CAR-positive T cells infiltrated into lymphoma tissue | Total number of CAR-positive T cells infiltrated into lymphoma tissue | 6 months |