Efficacy and Safety of PZ01 Treatment in Patients With r/r CD19+ B-cell Acute Lymphoblastic Leukemia/B Cell Lymphoma

Study Overview
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Brief Summary
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The major aim of this research is to assess the feasibility, safety and effectiveness of CD19 CAR-T Cell Therapy for Relapsed/ Refractory Acute Lymphoblastic Leukemia/ B cell Lymphoma patients who have applied it.

Official Title
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Study of Anti-CD19 Chimeric Antigen Receptor T Cells（PZ01） for Relapsed/ Refractory B-cell Acute Lymphoblastic Leukemia/B Cell Lymphoma

Conditions
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B-cell Acute Lymphoblastic Leukemia, B-cell Lymphoma

Intervention / Treatment
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* Drug: PZ01 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects or their legal guardians participate in this experiment voluntarily and informed consent form must be signed In accordance with National Comprehensive Cancer Network (NCCN) ALL Guidelines for Patients (2016, v.1) and CD19+B-ALL/B cell lymphoma patients diagnosed by histology In accordance with r/r CD19+ B-ALL/B cell lymphoma diagnosis, including any of the following situations: Getting through 2 treatments of standard chemotherapy with CR not yet obtained Reach CR for the first inducement, but CR lasts for ≦12 months r/r CD19+ B-ALL/B cell lymphoma for no positive effect after first or repeated remedial treatment ≧2 times of recurrence Remedial chemotherapy is not used within 4 weeks before cell therapy Immunosuppressive drug is not used within 4 weeks before cell therapy, including but not limited to systemic hormone therapy Antibody drug treatment is not received within 2 weeks before cell therapy Normal cardiac motion shown by echocardiography, left ventricular ejection fraction (LVEF) ≥50%, with no pericardial effusion and severe symptoms of cardiac arrhythmia No pulmonary active infection is found, with normal pulmonary function and indoor air SaO2 ≧92% No contraindications for leukapheresis Expected survival >3 months Grade 0 or 1 of ECOG performance status Exclusion Criteria: Pregnant and breastfeeding women Uncontrolled active infection Uncontrolled infectious disease is diagnosed, such as HIV, syphilis, hepatitis A, hepatitis B, hepatitis C and E. Patients who have used a large amount of glucocorticoid or other immunosuppressive drugs within 4 weeks Stage II-IV Acute/chronic general graft versus host disease Gene therapy has been undergone in the past

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 65 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: PZ01 CAR-T Cells<br>This is a phase I study. Patients with relapsed/ refractory B-cell Acute Lymphoblastic Leukemia/B cell Lymphoma are eligible for enrollment. | Drug: PZ01 CAR-T cells<br>* Chimeric antigen receptor (CAR) T cells targeting CD19 will be evaluated for safety and efficacy in patients with relapsed/ refractory B-cell Acute Lymphoblastic Leukemia/B cell Lymphoma. The CAR consists of a CD19 targeting antibody scFv with two intracellular signaling domains derived from CD3 zeta and 4-1BB. Autologous T cells will be gene-engineered with the CAR gene using a lentivirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Related Adverse Events | To evaluate the safety of adoptive transfer of gene-modified autologous CD19-specific T cells in relapsed/ refractory B-cell Acute Lymphoblastic Leukemia/B cell Lymphoma. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Proportion of patients with reduction in tumor burden. | 2 months | 
| Overall survival (OS) | Time from study enrollment until death. | 6 months | 
| Minimal residual disease negative remission rate(MRD) | Proportion of MRD-negative patients. | 2 months |