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

Primary Purpose

Lymphoma, B-Cell

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ET190L1 ARTEMIS™ T cells
Sponsored by
Eureka Therapeutics Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, B-Cell focused on measuring relapsed/refractory CD19+ Lymphomas, B-Cell

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Peking University Cancer Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

i.v. arm

Arm Description

ET190L1 ARTEMIS™ T cells administered by intravenous (IV) infusion

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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).
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).

Secondary Outcome Measures

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).
Anti-tumor responses
Progression free survival (PFS) and Median survival (MS) at 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.

Full Information

First Posted
January 23, 2018
Last Updated
March 12, 2021
Sponsor
Eureka Therapeutics Inc.
Collaborators
Peking University
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1. Study Identification

Unique Protocol Identification Number
NCT03415399
Brief Title
Clinical Study of ET190L1 ARTEMIS™ in Relapsed, Refractory B Cell Lymphoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
September 9, 2017 (Actual)
Primary Completion Date
December 31, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eureka Therapeutics Inc.
Collaborators
Peking University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, B-Cell
Keywords
relapsed/refractory CD19+ Lymphomas, B-Cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
i.v. arm
Arm Type
Experimental
Arm Description
ET190L1 ARTEMIS™ T cells administered by intravenous (IV) infusion
Intervention Type
Biological
Intervention Name(s)
ET190L1 ARTEMIS™ T cells
Intervention Description
Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) ARTEMIS™ expression construct
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
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.
Time Frame
28 days up to 24 months
Title
Toxicity profile of ET190L1 ARTEMIS™ T-cell treatment
Description
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.
Time Frame
28 days up to 24 months
Title
Tmax of serum cytokine levels
Description
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.
Time Frame
24 weeks
Title
Time to baseline for serum cytokine levels
Description
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.
Time Frame
24 weeks
Title
AUC of serum cytokine levels
Description
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 Frame
24 weeks
Title
Duration of in vivo engraftment of ET190L1 ARTEMIS™ T cells
Description
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).
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Rate of disease response
Description
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).
Time Frame
28 days to 24 months
Title
Anti-tumor responses
Description
Progression free survival (PFS) and Median survival (MS) at 4 months, 1 year, 2 years
Time Frame
4 months, 1 year, 2 years
Title
B cell depletion
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Zhu, MD
Organizational Affiliation
Peking University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University Cancer Hospital
City
Beijing
ZIP/Postal Code
100015
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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