ET190L1-ARTEMIS™ T Cells in Relapsed, Refractory B Cell Leukemia and Lymphoma

March 27, 2019 updated by: First Affiliated Hospital Xi'an Jiaotong University

Phase 1, Open-label, Single-arm, Dose-escalation Clinical Study Evaluating the Safety and Efficacy of ET190L1-ARTEMIS™2 in Relapsed, Refractory B Cell Leukemia and Lymphoma

Clinical study to evaluate safety and pharmacokinetics (primary objectives) and efficacy (secondary objective) of ET190L1-ARTEMIS™2 T-cells in patients with Cluster of Differentiation (CD) 19+ B cell Leukemia and Lymphoma

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

ARTEMIS™ is a novel chimeric T-cell therapy that in pre-clinical studies, functionally matches the efficacy of Chimeric Antigen Receptor (CAR) T cells, but dramatically reduces the release of cytokines upon killing of target positive tumors. The molecular target for ET190L1-ARTEMIS™ is Cluster of Differentiation 19 (CD19), which is expressed on B cell Lymphomas and B cell Leukemias. ET190L1-ARTEMIS™ is a second generation ARTEMIS™ receptor engineered with a human Fab antibody domain against CD19. This clinical study evaluates the safety and pharmacokinetics of ET190L1-ARTEMIS™ T-cells in patients with relapsed/refractory B-cell lymphoma and B-cell Leukemia.

Study Type

Interventional

Enrollment (Anticipated)

18

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Xi'an, China, 710061
        • Recruiting
        • First Affiliated Hospital of Xi'an Jiaotong University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with relapsed/refractory CD19+ B-cell lymphoma or Leukemia, with no effective therapy available per National Comprehensive Cancer Network (NCCN) guidelines
  • Eastern Cooperative Oncology Group (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.
  • Peripheral venous access is available and no issues with apheresis for lymphocyte isolation
  • serum alanine aminotransferase(ALT)<200 Unit/L, ALT/Aspartate aminotransferase(AST)<3 normal range; serum creatinine (Cr)<2.5mg/dL
  • 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
  • Patients with dependence on corticosteroids
  • Continuously used glucocorticoids or other immunosuppressive agents within 2 weeks
  • T cell deficiency or T cells are difficult to be transduced
  • Patients currently receiving other investigational treatments (biotherapy, chemotherapy, or radiotherapy)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: iv low dose
Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with low dose (1x10^6) in Leukemia or Lymphoma patients
Biological: ET190L1-ARTEMIS™ T cells -iv low dose
Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 1x10^6
EXPERIMENTAL: iv middle dose
Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with middle dose (3x10^6) in Leukemia or Lymphoma patients
Biological: ET190L1-ARTEMIS™ T cells -iv middle dose
Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 3x10^6
EXPERIMENTAL: iv high dose
Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with high dose (10x10^6) in Leukemia or Lymphoma patients
Biological: ET190L1-ARTEMIS™ T cells - iv high dose
Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 10x10^6

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of ARTEMIS T cell treatment-related adverse events
Time Frame: until 24 weeks
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™ T 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.
until 24 weeks
Number of ET190L1-ARTEMIS™ T cells in peripheral blood
Time Frame: 24 months
Duration of in vivo engraftment of ET190L1-ARTEMIS™ T cells. Number of ET190L1-ARTEMIS™ T cells in peripheral blood will be presented as Time to peak, Time to baseline level and so on.
24 months
% of ET190L1-ARTEMIS™ T cells in peripheral blood
Time Frame: 24 months
Duration of in vivo engraftment of ET190L1-ARTEMIS™ T cells. % of ET190L1-ARTEMIS™ T cells in peripheral blood will be presented as Time to peak, Time to baseline level and so on.
24 months
Maximum Tolerated Dose
Time Frame: 28 days up to 2 years
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 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tmax of serum cytokine levels
Time Frame: 24 weeks
Increase 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 Immunoassays will be presented as time to peak level.
24 weeks
Time to baseline for serum cytokine levels
Time Frame: 24 weeks
Increase 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 Immunoassays will be presented as time to baseline.
24 weeks
AUC of serum cytokine levels
Time Frame: 24 weeks
Increase 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 Immunoassays will be presented as area under curve (AUC).
24 weeks
Rate of disease response
Time Frame: 28 days to 24 months
Rate of disease response assessed by Lugano classification (a lymphoma staging classification). Response rates will be estimated as the percent of patients with any of the following: complete remission (CR), partial response (PR).
28 days to 24 months
Progression free survival (PFS)
Time Frame: 4 months, 1 year and 2 years
Progression free survival (PFS)
4 months, 1 year and 2 years
Median Survival（MS）
Time Frame: 4 months, 1 year and 2 years
Median Survival（MS）
4 months, 1 year and 2 years
Overall Survival（OS）
Time Frame: 4 months, 1 year and 2 years
Overall Survival（OS）
4 months, 1 year and 2 years
B cell depletion (Number)
Time Frame: 2 years
Number 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
B cell depletion (%)
Time Frame: 2 years
% 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

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital Xi'an Jiaotong University

Collaborators

Eureka Therapeutics Inc.

Investigators

  • Principal Investigator: Mei Zhang, PhD, First Affiliated Hospital Xi'an Jiaotong University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 6, 2017

Primary Completion (ANTICIPATED)

December 6, 2019

Study Completion (ANTICIPATED)

December 6, 2019

Study Registration Dates

First Submitted

March 26, 2019

First Submitted That Met QC Criteria

March 27, 2019

First Posted (ACTUAL)

March 29, 2019

Study Record Updates

Last Update Posted (ACTUAL)

March 29, 2019

Last Update Submitted That Met QC Criteria

March 27, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XJTU1AF2017LSL-C001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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