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

Phase 1

Completed

• Conditions: Lymphoma, B-Cell

• Registration Number: NCT03415399
• Lead Sponsor: Eureka Therapeutics Inc.

Brief Summary

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

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.

Study Timeline

• Study Start: 2017-09-09
• Study First Submitted: 2018-01-23
• Study First Submitted QC: 2018-01-23
• Study First Posted: 2018-01-30
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-12
• Last Update Posted: 2021-03-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose	28 days up to 24 months	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.
Toxicity profile of ET190L1 ARTEMIS™ T-cell treatment	28 days up to 24 months	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.
Tmax of serum cytokine levels	24 weeks	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.
AUC of serum cytokine levels	24 weeks	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).
Time to baseline for serum cytokine levels	24 weeks	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.
Duration of in vivo engraftment of ET190L1 ARTEMIS™ T cells	24 months	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).

Secondary Outcome Measures

Name	Time	Method
Rate of disease response	28 days to 24 months	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).
Anti-tumor responses	4 months, 1 year, 2 years	Progression free survival (PFS) and Median survival (MS) at 4 months, 1 year, 2 years
B cell depletion	2 years	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.

Trial Locations

Locations (1)

Peking University Cancer Hospital; 🇨🇳 Beijing, China