Safety and Efficacy of ThisCART19 in Patients With Refractory or Relapsed B Cell Malignancies

Study Overview
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Brief Summary
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This is a study to evaluate the safety and clinical activity of ThisCART19 (Allogeneic CAR-T targeting CD19) in patients with refractory or relapsed CD19 positive B cell malignancies.

Detailed Description
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This is a single-center, nonrandomized, open-label study to evaluate the safety and clinical activity of ThisCART19 in patients with refractory or relapsed CD19 positive B cell malignancies, such as acute or chronic lymphocytic leukemia, lymphoma and etc. The dose range is 0.2-60 x 10^6 cells per kg body weight.

Official Title
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A Study to Evaluate the Safety and Clinical Activity of Allogeneic Chimeric Antigen Receptor T Cells Targeting CD19 in Patients With Refractory or Relapsed B Cell Malignancies.

Conditions
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B Cell Malignancy

Intervention / Treatment
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* Biological: ThisCART19 cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with relapsed or refractory CD19 positive acute or chronic lymphocytic leukemia, or lymphoma. No alternative treatment options deemed by investigator. Measurable or detectble disease at time of enrollment. Eastern cooperative oncology group (ECOG) performance status of ≤2. Cardiac ejection fraction ≥ 40%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO). Estimated life expectancy > 12 weeks deemed by investigator. Serum creatinine ≤1.6 mg/dl and/or blood urea nitrogen(BUN) ≤ 1.5 mg/dl . Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 upper limit of normal (ULN). Informed consent explained to, understood by and signed by patient/guardian. Exclusion Criteria: Pregnant or lactating women Uncontrolled infection Active hepatitis B virus or hepatitis C virus infection. Patients who need steroids to control disease. Patients who accepted autologous stem-cell transplantation (ASCT) within 100 days. Patients with grade 2-4 graft-versus-host disease (GVHD), or deemed need to manage by investigator. History of Human Immunodeficiency Virus (HIV) infection. Patients with active central nervous system (CNS) involvement by malignancy. Patients combine with other disease cause neutrophil count (ANC) < 750 per microlitre or platelet count (PLT)< 50,000 per microlitre.

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ThisCART19 cells injections<br>In this study, allogeneic anti-CD19 CAR T Cells(ThisCART19 cells) is used to treat patients with refractory or relapsed CD19 positive B cell malignancies. | Biological: ThisCART19 cells<br>* 0.2-60 x 10^6 CAR T cells per kg body weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose Limiting Toxicities | To assess adverse events as dose limiting toxicities as defined by the protocol. | From infusion to Day 28 | 
| Complete Remission | Proportion of patients in whom with morphologic complete remission (CR) | At Day 28 after ThisCART19 infusion | 
| TRM: Treatment Related Mortality | The mortality related with ThisCART19 infusion. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | For Acute Lymphoblastic Leukemia (ALL), Objective response rate(ORR) is the percentage of patients who achieve CR or chronic lymphocytic leukemia(CRi); for chronic lymphocytic leukemia (CLL) and lymphoma, ORR is the incidence of either a complete response (CR) or a partial response (PR). | Up to 1 year | 
| Duration of Response | Duration of Response (DOR) defined as the duration (days) from initial response to disease relapse, progression, or death due to any course. | Up to 1 year | 
| Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability | Adverse events assessed according to NCI-CTCAE v5.0 criteria | From inclusion up to 1 year | 
| Overall Survival Rate of 2 Years | The rate of patients whom alive at year 2 | At year 2 |