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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma, B-Cell
• Intervention / Treatment: Biological: ET190L1 ARTEMIS™ T cells

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 Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100015
    • Peking University Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: i.v. arm; ET190L1 ARTEMIS™ T cells administered by intravenous (IV) infusion	Biological: ET190L1 ARTEMIS™ T cells; Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) ARTEMIS™ expression construct

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Anti-tumor responses	Progression free survival (PFS) and Median survival (MS) at 4 months, 1 year, 2 years	4 months, 1 year, 2 years
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
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

Collaborators and Investigators

• Sponsor: Eureka Therapeutics Inc.
• Collaborators: Peking University
• Investigators: Principal Investigator: Jun Zhu, MD, Peking University

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2017
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: January 23, 2018
• First Submitted That Met QC Criteria: January 23, 2018
• First Posted (Actual): January 30, 2018

Study Record Updates

• Last Update Posted (Actual): March 16, 2021
• Last Update Submitted That Met QC Criteria: March 12, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: relapsed/refractory CD19+ Lymphomas, B-Cell
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: ETCH17CD19AR103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No