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

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ClinicalTrials.gov Identifier: NCT03895944
Recruitment Status : Unknown
Verified March 2019 by First Affiliated Hospital Xi'an Jiaotong University.
Recruitment status was:  Recruiting
First Posted : March 29, 2019
Last Update Posted : March 29, 2019
Sponsor:
Collaborator:
Eureka Therapeutics Inc.
Information provided by (Responsible Party):
First Affiliated Hospital Xi'an Jiaotong University

Study Description
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Brief Summary:
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

Condition or disease Intervention/treatment Phase
CD19+ Lymphoma, B-Cell CD19+ Leukemia, B-Cell Biological: ET190L1-ARTEMIS™ T cells -iv low dose Biological: ET190L1-ARTEMIS™ T cells -iv middle dose Biological: ET190L1-ARTEMIS™ T cells - iv high dose Early Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 6, 2017
Estimated Primary Completion Date : December 6, 2019
Estimated Study Completion Date : December 6, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia Lymphoma

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.

  3. % 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.

  4. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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).

  4. 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).

  5. Progression free survival (PFS) [ Time Frame: 4 months, 1 year and 2 years ]
    Progression free survival (PFS)

  6. Median Survival（MS） [ Time Frame: 4 months, 1 year and 2 years ]
    Median Survival（MS）

  7. Overall Survival（OS） [ Time Frame: 4 months, 1 year and 2 years ]
    Overall Survival（OS）

  8. 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.

  9. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03895944


Contacts
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Contact: Mei Zhang, PhD 86-18991232153 prozhangmei@126.com

Locations
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China
First Affiliated Hospital of Xi'an Jiaotong University Recruiting
Xi'an, China, 710061
Contact: Mei Zhang, PhD    86-18991232153    prozhangmei@126.com   
Sponsors and Collaborators
First Affiliated Hospital Xi'an Jiaotong University
Eureka Therapeutics Inc.
Investigators
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Principal Investigator: Mei Zhang, PhD First Affiliated Hospital Xi'an Jiaotong University
More Information
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Responsible Party: First Affiliated Hospital Xi'an Jiaotong University
ClinicalTrials.gov Identifier: NCT03895944    
Other Study ID Numbers: XJTU1AF2017LSL-C001
First Posted: March 29, 2019    Key Record Dates
Last Update Posted: March 29, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Lymphoma, B-Cell
Leukemia, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid