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ET140203 T Cells in Pediatric Subjects With Hepatoblastoma, HCN-NOS, or Hepatocellular Carcinoma (ARYA-2)

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ClinicalTrials.gov Identifier: NCT04634357
Recruitment Status : Not yet recruiting
First Posted : November 18, 2020
Last Update Posted : October 8, 2021
Sponsor:
Information provided by (Responsible Party):
Eureka Therapeutics Inc.

Brief Summary:
Open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety/tolerability and determine the recommended Phase II Dose (RP2D) of ET140203 T-cells in pediatric subjects who are AFP-positive/HLA-A2-positive and have relapsed/refractory HB, HCN-NOS, or HCC.

Condition or disease Intervention/treatment Phase
Hepatoblastoma Hepatocellular Carcinoma (HCC) Liver Neoplasms Metastatic Liver Cancer Liver Cancer HEMNOS Drug: ET140203 T Cells Phase 1 Phase 2

Detailed Description:

The trial starts with a dose escalation phase. A traditional dose escalation model (3+3) design will be used to determine the recommended phase II dose (RP2D). Subjects will then be treated at the RP2D in the expansion phase of the trial.

Following treatment, tumor response assessments will be performed at Months 1, 3, 6, 9, 12, 18, and 24. At each tumor response assessment visit, imaging will be performed (triphasic CT Scan) and used for response evaluation. Serum AFP levels will also be measured at each tumor response assessment visit.

The active assessment phase of the study will continue for 2 years. Subjects will be followed for 15 years post-treatment for assessment of treatment safety and overall survival.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Dose Escalation, Phase I/II Clinical Trial of ET140203 T Cells in Pediatric Subjects With Relapsed/Refractory Hepatoblastoma (HB), Hepatocellular Neoplasm-Not Otherwise Specified (HCN-NOS), or Hepatocellular Carcinoma (HCC)
Estimated Study Start Date : October 15, 2021
Estimated Primary Completion Date : February 28, 2023
Estimated Study Completion Date : February 28, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ET140203 T Cells
ET140203 T Cells
Drug: ET140203 T Cells

Biological/Vaccine: ET140203 autologous T-cell product

Autologous T cells transduced with lentivirus encoding an ET140203 expression construct





Primary Outcome Measures :
  1. Incidence rates of adverse events (AEs) after infusion of ET140203 T cells [ Time Frame: 28 days ]
    Safety of ET140203 T cells as assessed by the number of adverse events (AEs) after infusion

  2. Severity rates of adverse events (AEs) after infusion of ET140203 T cells [ Time Frame: 28 days ]
    Safety of ET140203 T cells as assessed by the severity of adverse events (AEs) after infusion.

  3. Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells [ Time Frame: 28 days ]
    Tolerability of ET140203 T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)

  4. The recommended phase 2 dose (RP2D) regimen of ET140203 T cell therapy primarily based on DLT [ Time Frame: Up to 2 years ]
    The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLTs.


Secondary Outcome Measures :
  1. Assess the efficacy of ET140203 T cells in pediatric subjects with relapsed/refractory HB, HCN-NOS, or HCC [ Time Frame: Up to 2 years ]
    Response rate will be assessed by radiographic scans and assessed according to RECIST criteria.

  2. Determine the pharmacokinetics of ET140203 T cells after infusion. [ Time Frame: Up to 2 years ]
    Assess the expansion and persistence of ET140203 T cells circulating in blood over time.



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed HB, HCN-NOS, or HCC with serum AFP >200ng/ml at the time of screening and following the most recent line of therapy.
  2. Disease reoccurrence after remission following initial standard-of-care (SOC) treatment (i.e. relapse) or failure of response to SOC treatment (i.e. refractory).
  3. Age ≥ 1 year and ≤ 21 years.
  4. Molecular Human Leukocyte Antigen (HLA) class I allele typing that confirms subject carries at least one HLA-A2 allele.
  5. Life expectancy of > 4 months per Principal Investigator's opinion.
  6. Lansky or Karnofsky Performance Scale ≥ 70.
  7. For enrollment to the dose-finding cohort, subjects must have at least one (1) lesion ≥ 5 mm in diameter or two (2) or more lesions ≥ 3 mm in diameter. For the dose-expansion cohort, subjects must have measurable disease by RECIST v1.1.
  8. Child-Pugh score of B7 or better.
  9. Adequate organ function.

Exclusion Criteria:

  1. Received the following within two (2) weeks of leukapheresis and within two (2) weeks of conditioning chemotherapy: cytotoxic chemotherapy, radiation, systemic corticosteroids, other anti-cancer therapies (including immunotherapeutic agents), or any other immunosuppressive agents (Note: use of inhaled or topical steroids is not exclusionary).
  2. Concurrently receiving other investigational agents, biological, chemical, or radiation therapies, while participating in the study.
  3. Contraindication for receipt of conditioning chemotherapeutic agents including Fludarabine and Cyclophosphamide.
  4. Active autoimmune disease requiring systemic immunosuppressive therapy.
  5. Compromised circulation in the main portal vein, hepatic vein, or vena cava due to partial or complete obstruction which, in the opinion of the Principal Investigator, would make the subject unsuitable for the study.
  6. History of organ transplant.
  7. HB, HCN-NOS, or HCC involving greater than 50% of the liver (volumetric).

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): NCT04634357


Contacts
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Contact: Karen B Cravotto 510-722 8719 karen.cravotto@eurekainc.com
Contact: Pei Wang, PhD 510-654 7045 pei.wang@eurekainc.com

Locations
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United States, Massachusetts
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
Boston, Massachusetts, United States, 02215
Contact: Allison O'Neill, MD    617-632-4202    Allison_ONeill@DFCI.HARVARD.EDU   
Sponsors and Collaborators
Eureka Therapeutics Inc.
Investigators
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Study Director: Pei Wang, PhD Eureka Therapeutics Inc.
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Responsible Party: Eureka Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT04634357    
Other Study ID Numbers: ETUS20AFPAR123
First Posted: November 18, 2020    Key Record Dates
Last Update Posted: October 8, 2021
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eureka Therapeutics Inc.:
Relapsed/Refractory Hepatoblastoma (HB)
Pediatric
Hepatocellular Neoplasm-Not Otherwise Specified (HCN-NOS)
Hepatocellular Carcinoma (HCC)
Liver Cancer
T-cell therapy
Metastatic Liver Cancer
Liver neoplasms
HEMNOS
Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Carcinoma, Hepatocellular
Liver Neoplasms
Hepatoblastoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Neoplasms, Complex and Mixed