ET190L1-ARTEMIS™ T Cells in Relapsed, Refractory B Cell Leukemia and Lymphoma

Study Overview
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Brief Summary
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Clinical study to evaluate safety and pharmacokinetics (primary objectives) and efficacy (secondary objective) of ET190L1-ARTEMIS™2 T-cells in patients with Cluster of Differentiation (CD) 19+ B cell Leukemia and Lymphoma

Detailed Description
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ARTEMIS™ is a novel chimeric T-cell therapy that in pre-clinical studies, functionally matches the efficacy of Chimeric Antigen Receptor (CAR) T cells, but dramatically reduces the release of cytokines upon killing of target positive tumors. The molecular target for ET190L1-ARTEMIS™ is Cluster of Differentiation 19 (CD19), which is expressed on B cell Lymphomas and B cell Leukemias. ET190L1-ARTEMIS™ is a second generation ARTEMIS™ receptor engineered with a human Fab antibody domain against CD19. This clinical study evaluates the safety and pharmacokinetics of ET190L1-ARTEMIS™ T-cells in patients with relapsed/refractory B-cell lymphoma and B-cell Leukemia.

Official Title
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Phase 1, Open-label, Single-arm, Dose-escalation Clinical Study Evaluating the Safety and Efficacy of ET190L1-ARTEMIS™2 in Relapsed, Refractory B Cell Leukemia and Lymphoma

Conditions
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CD19+ Lymphoma, B-Cell, CD19+ Leukemia, B-Cell

Intervention / Treatment
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* Biological: ET190L1-ARTEMIS™ T cells -iv low dose
* Biological: ET190L1-ARTEMIS™ T cells -iv middle dose
* Biological: ET190L1-ARTEMIS™ T cells - iv high dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with relapsed/refractory CD19+ B-cell lymphoma or Leukemia, with no effective therapy available per National Comprehensive Cancer Network (NCCN) guidelines Eastern Cooperative Oncology Group (ECOG) performance status ≤2, expected survival time > 3 months per PIs opinion Women of childbearing age should have a negative pregnancy test and agree to use effective contraception during treatment and 1 year after the last dose. Peripheral venous access is available and no issues with apheresis for lymphocyte isolation serum alanine aminotransferase(ALT)<200 Unit/L, ALT/Aspartate aminotransferase(AST)<3 normal range; serum creatinine (Cr)<2.5mg/dL Voluntarily signed informed consent form Exclusion Criteria: Women in pregnancy and lactation Unable to perform leukapheresis and iv infusion With active infection Major organ failure Patients with dependence on corticosteroids Continuously used glucocorticoids or other immunosuppressive agents within 2 weeks T cell deficiency or T cells are difficult to be transduced Patients currently receiving other investigational treatments (biotherapy, chemotherapy, or radiotherapy)

Ages Eligible for Study
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Minimum Age: 18 Years
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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iv low dose<br>Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with low dose (1x10^6) in Leukemia or Lymphoma patients | Biological: ET190L1-ARTEMIS™ T cells -iv low dose<br>* Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 1x10^6<br>|
| Experimental: iv middle dose<br>Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with middle dose (3x10^6) in Leukemia or Lymphoma patients | Biological: ET190L1-ARTEMIS™ T cells -iv middle dose<br>* Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 3x10^6<br>|
| Experimental: iv high dose<br>Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with high dose (10x10^6) in Leukemia or Lymphoma patients | Biological: ET190L1-ARTEMIS™ T cells - iv high dose<br>* Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 10x10^6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of ARTEMIS T cell treatment-related adverse events | Frequency of treatment-related adverse events that occurred at any time from the first day of infusion that are possibly, likely, or definitely related to the study, including infusion related toxicity and ET190L1-ARTEMIS™ T T cells related toxicity. Include but not limited to: Fever, chills, nausea, vomiting, jaundice and other gastrointestinal symptoms; Fatigue, hypotension, respiratory distress; Tumor lysis syndrome; Cytokine release syndrome; Neutropenia, thrombocytopenia; Liver and kidney dysfunction. Assessed at all visits. | until 24 weeks | 
| Number of ET190L1-ARTEMIS™ T cells in peripheral blood | Duration of in vivo engraftment of ET190L1-ARTEMIS™ T cells. Number of ET190L1-ARTEMIS™ T cells in peripheral blood will be presented as Time to peak, Time to baseline level and so on. | 24 months | 
| % of ET190L1-ARTEMIS™ T cells in peripheral blood | Duration of in vivo engraftment of ET190L1-ARTEMIS™ T cells. % of ET190L1-ARTEMIS™ T cells in peripheral blood will be presented as Time to peak, Time to baseline level and so on. | 24 months | 
| Maximum Tolerated Dose | Determine the safety, including potential dose limiting toxicities, of the ET190L1-ARTEMIS™ T cells. A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ET190L1-ARTEMIS™ T cells, which is irreversible or life threatening or CTCAE Grade 3-5. Assessed at all visits. | 28 days up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax of serum cytokine levels | Increase or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immunoassays will be presented as time to peak level. | 24 weeks | 
| Time to baseline for serum cytokine levels | Increase or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immunoassays will be presented as time to baseline. | 24 weeks | 
| AUC of serum cytokine levels | Increase or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immunoassays will be presented as area under curve (AUC). | 24 weeks | 
| Rate of disease response | Rate of disease response assessed by Lugano classification (a lymphoma staging classification). Response rates will be estimated as the percent of patients with any of the following: complete remission (CR), partial response (PR). | 28 days to 24 months | 
| Progression free survival (PFS) | Progression free survival (PFS) | 4 months, 1 year and 2 years | 
| Median Survival（MS） | Median Survival（MS） | 4 months, 1 year and 2 years | 
| Overall Survival（OS） | Overall Survival（OS） | 4 months, 1 year and 2 years | 
| B cell depletion (Number) | Number of B cells in peripheral blood will be presented as time to baseline level and time to recover for up to 2 years. | 2 years | 
| B cell depletion (%) | % of B cells in peripheral blood will be presented as time to baseline level and time to recover for up to 2 years. | 2 years |