Back to resultsET190L1-ARTEMIS™ T Cells in Relapsed, Refractory B Cell Leukemia and Lymphoma
Primary Purpose
CD19+ Lymphoma, B-Cell, CD19+ Leukemia, B-Cell
Status
Unknown status
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
ET190L1-ARTEMIS™ T cells -iv low dose
ET190L1-ARTEMIS™ T cells -iv middle dose
ET190L1-ARTEMIS™ T cells - iv high dose
Sponsored by
About this trial
This is an interventional treatment trial for CD19+ Lymphoma, B-Cell
Eligibility 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)
Sites / Locations
- First Affiliated Hospital of Xi'an Jiaotong UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
iv low dose
iv middle dose
iv high dose
Arm Description
Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with low dose (1x10^6) in Leukemia or Lymphoma patients
Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with middle dose (3x10^6) in Leukemia or Lymphoma patients
Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with high dose (10x10^6) in Leukemia or Lymphoma patients
Outcomes
Primary Outcome Measures
Frequency of ARTEMIS T cell treatment-related adverse events
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.
Number of ET190L1-ARTEMIS™ T cells in peripheral blood
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.
% of ET190L1-ARTEMIS™ T cells in peripheral blood
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.
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.
Secondary Outcome Measures
Tmax of serum cytokine levels
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.
Time to baseline for serum cytokine levels
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.
AUC of serum cytokine levels
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).
Rate of disease response
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).
Progression free survival (PFS)
Progression free survival (PFS)
Median Survival（MS）
Median Survival（MS）
Overall Survival（OS）
Overall Survival（OS）
B cell depletion (Number)
Number of B cells in peripheral blood will be presented as time to baseline level and time to recover for up to 2 years.
B cell depletion (%)
% 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
NCT ID
NCT03895944
First Posted
March 26, 2019
Last Updated
March 27, 2019
Sponsor
First Affiliated Hospital Xi'an Jiaotong University
Collaborators
Eureka Therapeutics Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03895944
Brief Title
ET190L1-ARTEMIS™ T Cells in Relapsed, Refractory B Cell Leukemia and Lymphoma
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 6, 2017 (Actual)
Primary Completion Date
December 6, 2019 (Anticipated)
Study Completion Date
December 6, 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
First Affiliated Hospital Xi'an Jiaotong University
Collaborators
Eureka Therapeutics Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CD19+ Lymphoma, B-Cell, CD19+ Leukemia, B-Cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
iv low dose
Arm Type
Experimental
Arm Description
Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with low dose (1x10^6) in Leukemia or Lymphoma patients
Arm Title
iv middle dose
Arm Type
Experimental
Arm Description
Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with middle dose (3x10^6) in Leukemia or Lymphoma patients
Arm Title
iv high dose
Arm Type
Experimental
Arm Description
Autologous ET190L1-ARTEMIS™ T cells administered by intravenous (IV) infusion with high dose (10x10^6) in Leukemia or Lymphoma patients
Intervention Type
Biological
Intervention Name(s)
ET190L1-ARTEMIS™ T cells -iv low dose
Intervention Description
Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 1x10^6
Intervention Type
Biological
Intervention Name(s)
ET190L1-ARTEMIS™ T cells -iv middle dose
Intervention Description
Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 3x10^6
Intervention Type
Biological
Intervention Name(s)
ET190L1-ARTEMIS™ T cells - iv high dose
Intervention Description
Autologous T cells transduced with lentivirus encoding an anti-CD19 (ET190L1) -ARTEMIS™ expression construct, 10x10^6
Primary Outcome Measure Information:
Title
Frequency of ARTEMIS T cell treatment-related adverse events
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™ 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.
Time Frame
until 24 weeks
Title
Number of ET190L1-ARTEMIS™ T cells in peripheral blood
Description
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.
Time Frame
24 months
Title
% of ET190L1-ARTEMIS™ T cells in peripheral blood
Description
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.
Time Frame
24 months
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 2 years
Secondary Outcome Measure Information:
Title
Tmax of serum cytokine levels
Description
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.
Time Frame
24 weeks
Title
Time to baseline for serum cytokine levels
Description
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.
Time Frame
24 weeks
Title
AUC of serum cytokine levels
Description
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).
Time Frame
24 weeks
Title
Rate of disease response
Description
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).
Time Frame
28 days to 24 months
Title
Progression free survival (PFS)
Description
Progression free survival (PFS)
Time Frame
4 months, 1 year and 2 years
Title
Median Survival（MS）
Description
Median Survival（MS）
Time Frame
4 months, 1 year and 2 years
Title
Overall Survival（OS）
Description
Overall Survival（OS）
Time Frame
4 months, 1 year and 2 years
Title
B cell depletion (Number)
Description
Number 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
Title
B cell depletion (%)
Description
% 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
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mei Zhang, PhD
Phone
86-18991232153
Email
prozhangmei@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mei Zhang, PhD
Organizational Affiliation
First Affiliated Hospital Xi'an Jiaotong University
Official's Role
Principal Investigator
Facility Information:
Facility Name
First Affiliated Hospital of Xi'an Jiaotong University
City
Xi'an
ZIP/Postal Code
710061
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mei Zhang, PhD
Phone
86-18991232153
Email
prozhangmei@126.com
12. IPD Sharing Statement
Learn more about this trial
ET190L1-ARTEMIS™ T Cells in Relapsed, Refractory B Cell Leukemia and Lymphoma
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