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Trial record 2 of 179 for:    DCLRE1C

ET1402L1-ARTEMIS™2 T Cells in Alpha Fetoprotein (AFP) Expressing Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT03888859
Recruitment Status : Recruiting
First Posted : March 25, 2019
Last Update Posted : March 27, 2019
Sponsor:
Collaborators:
Eureka Therapeutics Inc.
Aeon Therapeutics (Shanghai) Co., Ltd.
Information provided by (Responsible Party):
First Affiliated Hospital Xi'an Jiaotong University

Brief Summary:
Clinical study to evaluate safety (primary objectives) and efficacy (secondary objective) of ET1402L1-ARTEMIS™2 T cells in patients with alpha fetoprotein positive (AFP+ ) hepatocellular carcinoma (HCC).

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Liver Cancer Liver Neoplasms Metastatic Liver Cancer Biological: ET1402L1-ARTEMIS™ T cells -IV Biological: ET1402L1-ARTEMIS™ T cells -intra-hepatic artery Biological: ET1402L1-ARTEMIS™ T cells -Intratumoral Injections Early Phase 1

Detailed Description:

The molecular target for ET1402L1-ARTEMIS™2 is human leukocyte antigen (HLA) -A02 complexed with a HLA-A02-restricted peptide of alpha fetoprotein (AFP), which is expressed on 60-80 percent of hepatocellular carcinoma (HCC). ARTEMIS™2 is a second generation ARTEMIS™ receptor engineered with a human antibody domain against the anti-HLA-A02/AFP complex. This clinical study evaluates the safety and pharmacokinetics of ET1402L1-ARTEMIS™2 T-cells in patients with HCC who have no available curative therapeutic options and a poor overall prognosis.

Patients with lesion(s) localized in liver will be enrolled in the intra-hepatic artery (IA) arm or Intratumoral Injections arm, with the ET1402L1-ARTEMIS™2 T-cells administered via intrahepatic artery catheter. Patients with extrahepatic metastasis will be enrolled in the intravenous (IV) arm, with the ET1402L1-ARTEMIS™2 T-cells administered through intravenous infusion.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1, Open-label, Three Routes IV, Intratumoral Injections and Intra-hepatic Artery Dose-escalation Clinical Study to Evaluate the Safety and Efficacy of ET1402L1-ARTEMIS™2™ T- Cells in AFP Expressing Hepatocellular Carcinoma (HCC)
Actual Study Start Date : December 6, 2017
Estimated Primary Completion Date : December 6, 2019
Estimated Study Completion Date : January 6, 2020

Arm Intervention/treatment
Experimental: Intravenous (i.v.) arm
autologous ET1402L1-ARTEMIS™2 T cells administered by intravenous (IV) infusion
Biological: ET1402L1-ARTEMIS™ T cells -IV
Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct -intravenous (i.v.) arm

Experimental: Intra-hepatic artery (i.a.) arm
autologous ET1402L1-ARTEMIS™2 T cells administered by intra-hepatic artery (IA) infusion
Biological: ET1402L1-ARTEMIS™ T cells -intra-hepatic artery
Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct: intra-hepatic artery (i.a.) arm

Experimental: Intratumoral Injections (i.t.) arm
autologous ET1402L1-ARTEMIS™2 T cells administered by intratumoral injections (i.t.) infusion
Biological: ET1402L1-ARTEMIS™ T cells -Intratumoral Injections
Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct: Intratumoral Injections (i.t.) arm




Primary Outcome Measures :
  1. Number of patients with dose-limiting toxicity [ Time Frame: 28 days up to 2 years ]
    A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ET1402L1-ARTEMIS™2 T-cells, which is irreversible, or life threatening or CTCAE Grade 3-5. Assessed at all visits.

  2. Frequency of ARTEMIS T cell treatment-related adverse events [ Time Frame: Time Frame: 28 days up to 2 years ]
    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.


Secondary Outcome Measures :
  1. Rate of disease response by RECIST in the liver [ Time Frame: 2 years ]
    Response rates will be estimated as the percent of patients with objective response (OR),which was defined as any of complete remission (CR), partial response (PR) at 2 years.

  2. Rate of disease response by RECIST at non-liver sites [ Time Frame: 2 years ]
    Response rates will be estimated as the percent of patients with objective response (OR),which was defined as any of complete remission (CR), partial response (PR) at 2 years.

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

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

  5. Overall survival(OS) [ Time Frame: at 2 years ]
    overall survival(OS)at 2 years

  6. AFP serum levels [ Time Frame: 2 years ]
    Percent change compared to the baseline

  7. Number of ET1402L1-ARTEMIS™2 T cells in peripheral blood [ Time Frame: 2 years ]
    Number of ET1402L1-ARTEMIS™2 T cells in peripheral blood will be presented as Time to peak, Time to baseline level

  8. % of ET1402L1-ARTEMIS™2 T cells in peripheral blood [ Time Frame: 2 years ]
    %of ET1402L1-ARTEMIS™2 T cells in peripheral blood will be presented as Time to peak, Time to baseline level

  9. AFP expression in tumors [ Time Frame: 4-8 weeks ]
    Percent of AFP-positive cells in randomly selected fields in tumor biopsies.

  10. Tmax of serum Interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor necrosis factor(TNF)-α and Interferon gamma (INFγ) [ Time Frame: 24 weeks ]
    Increase or decreases in the amount of serum IL-2, IL-4, IL-6, IL-10, TNF-α and INF-γ produced compared to baseline at time points measured up to 24 weeks since dosing. Data will be presented as time to peak level for Tmax.

  11. AUC of serum IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ [ Time Frame: 24 weeks ]
    Increase or decreases in the amount of serum IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ produced compared to baseline at time points measured up to 24 weeks since dosing. Data will be presented as time to peak level for area under curve (AUC).

  12. Time to baseline for serum IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ [ Time Frame: 24 weeks ]
    Increase or decreases in the amount of IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ produced compared to baseline at time points measured up to 24 weeks since dosing.



Information from the National Library of Medicine

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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:

  • AFP-expressing HCC and serum AFP >100 ng/mL.
  • Abandon or failure in first or second line treatment
  • Molecular HLA class I typing confirms participant carries at least one HLA-A02 allele
  • Child-Pugh score of A or B, Barcelona Clinic Liver Cancer stage of C or D
  • Life expectancy > 4 months
  • Karnofsky score ≥70%
  • Adequate organ function as defined below:

    1. Patients must have a serum Total bilirubin ≤2 x Upper Limit of Normal (ULN), Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤5 times the institutional ULN.
    2. A pretreatment measured creatinine clearance (absolute value) of ≥ 50 ml/minute
    3. Ejection fraction measured by echocardiogram or Multiple gated acquisition scanning (MUGA) >45% (evaluation done with 6 weeks of screening does not need to be repeated)
    4. Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) or Forced Expiratory Volume in the first second (FEV1)>45% predicted
    5. Absolute neutrophil count (ANC) ≥ 1500/mm3 (10^9/L)
    6. Platelet count ≥ 50,000/mm3 (10^9/L)
  • Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

  • Patients with decompensated cirrhosis: Child-Pugh Score C
  • Patients with tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver.
  • Patients with an organ transplantation history
  • Patients with dependence on corticosteroids
  • Patients with active autoimmune diseases requiring systemic immunosuppressive therapy
  • Patients who are currently receiving or received within past 30 days anti-cancer therapy, local treatments for liver tumors (radiotherapy, embolism, ablation) or liver surgery
  • Patients currently receiving other investigational treatments (biotherapy, chemotherapy, or radiotherapy)
  • Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within two years. Patients with a history of successfully-treated tumors with no sign of recurrence in the last two years may be enrolled.
  • Patients with other uncontrolled diseases, such as active infections
  • Acute or chronic active hepatitis B or hepatitis C.
  • Women who are pregnant or breast-feed
  • HIV-infection

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): NCT03888859


Contacts
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Contact: Chang Liu, PhD 86-18991232095 eyrechang@126.com

Locations
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China
The First Affiliated Hospital of Xi'an Jiaotong University Recruiting
Xi'an, China, 710061
Contact: Chang Liu, PhD    86-18991232095    eyrechang@126.com   
Sponsors and Collaborators
First Affiliated Hospital Xi'an Jiaotong University
Eureka Therapeutics Inc.
Aeon Therapeutics (Shanghai) Co., Ltd.
Investigators
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Principal Investigator: Chang Liu, PhD First Affiliated Hospital Xi'an Jiaotong University

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Responsible Party: First Affiliated Hospital Xi'an Jiaotong University
ClinicalTrials.gov Identifier: NCT03888859     History of Changes
Other Study ID Numbers: XJTU1AF2017LSL-C002
First Posted: March 25, 2019    Key Record Dates
Last Update Posted: March 27, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases