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

Lymphoma, B-Cell Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03415399
• Other study ID #: ETCH17CD19AR103
• Status: Completed
• Phase: Phase 1
• Start date: September 9, 2017
• Est. completion date: December 31, 2020

Study information

• Verified date: March 2021
• Source: Eureka Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell

Intervention

Biological:
• ET190L1 ARTEMIS™ T cells
Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) ARTEMIS™ expression construct

Locations

Country	Name	City	State
China	Peking University Cancer Hospital	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Eureka Therapeutics Inc.	Peking University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	Anti-tumor responses	Progression free survival (PFS) and Median survival (MS) at 4 months, 1 year, 2 years	4 months, 1 year, 2 years
Secondary	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