Clinical Study of ET190L1 ARTEMIS™ in Relapsed, Refractory B Cell Lymphoma

Study Overview
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Brief Summary
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This study is to determine the safety, including potential dose limiting toxicities, of ET190L1 ARTEMIS™ T cells and the duration of in vivo survival of ET190L1 ARTEMIS™ T cells in patients with relasped/refractory B-cell lymphoma. For patients with detectable disease, the study will also measure anti-tumor responses after ET190L1 ARTEMIS™ cell infusions.

Detailed Description
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ET190L ARTEMIS™ is a novel chimeric T-cell therapy platform that in preclinical studies, functionally matches the efficacy of CAR T cells, but dramatically reduces the release of cytokines upon killing of target-positive tumors.

Official Title
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Phase 1, Open-label, Single-arm, Dose-escalation Clinical Study Evaluating the Safety and Efficacy of ET190L1 ARTEMIS™ (Anti-CD19-ARTEMIS™) in Relapsed, Refractory B Cell Lymphoma

Conditions
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Lymphoma, B-Cell

Intervention / Treatment
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* Biological: ET190L1 ARTEMIS™ T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with relapsed/refractory CD19+ B-cell lymphoma, with no effective therapy available per NCCN guidelines No HCV, HIV infection, no active HBV Liver and kidney function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) does not exceed five times the upper limit of normal range. ALT <200U / L, bilirubin <2.0 mg/ dL Renal function: creatinine <2.5mg / dL; Pre-treatment absolute creatinine clearance ≥50 mL / minute CBC: Hemoglobin ≥ 80g / L, Absolute Neutrophil Counts ≥1 × 10^9 / L, Platelets ≥50 × 10^9 / L Echocardiography or multiple gated angiogram (MUGA) ejection fraction> 45% 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. Had a recurrence after at least a first-line systemic treatment Peripheral venous access is available and no issues with apheresis for lymphocyte isolation 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 Continuously used glucocorticoids or other immunosuppressive agents within 4 weeks T cell deficiency or T cells are difficult to be transduced

Ages Eligible for Study
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Minimum Age: 18 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: i.v. arm<br>ET190L1 ARTEMIS™ T cells administered by intravenous (IV) infusion | Biological: ET190L1 ARTEMIS™ T cells<br>* Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) ARTEMIS™ expression construct<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 24 months | 
| Toxicity profile of ET190L1 ARTEMIS™ T-cell treatment | 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™-cell 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. | 28 days up to 24 months | 
| Tmax of serum cytokine levels | Increases 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 Immuoassays will be presented as time to peak level. | 24 weeks | 
| Time to baseline for serum cytokine levels | Increases 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 Immuoassays will be presented as Time to baseline. | 24 weeks | 
| AUC of serum cytokine levels | Increases 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 Immuoassays will be presented as area under curve (AUC). | 24 weeks | 
| Duration of in vivo engraftment of ET190L1 ARTEMIS™ T cells | Number and % of ET190L1 ARTEMIS™ T cells in peripheral blood will be presented as Time to peak, Time to baseline level and the overall exposure will be presented as area under curve (AUC). | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of disease response | Rate of disease response assessed by Lugano (Chason) classification. Response rates will be estimated as the percent of patients with complete remission (CR), partial response (PR), stable disease (SD), progression disease (PD), overall survival (OS). | 28 days to 24 months | 
| Anti-tumor responses | Progression free survival (PFS) and Median survival (MS) at 4 months, 1 year, 2 years | 4 months, 1 year, 2 years | 
| B cell depletion | Number and % 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsed/refractory CD19+ Lymphomas, B-Cell