Clinical Trials /

MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers

NCT02989064

Description:

This Phase 1 study is designed as a cell dose escalation trial in HLA-A*02:01 and HLA-A*02:06 subjects with MAGE-A10 positive urothelial, melanoma or head and neck tumors. The study will enroll subjects at least 18 years of age using a modified 3+3 cell dose escalation design, to evaluate dose limiting toxicities and determine the target cell dose range. Following the dose escalation phase, additional subjects will be enrolled at the target cell dose range to further characterize safety and the effects at this cell dose. The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. When the MAGE-A10ᶜ⁷⁹⁶T cells are available, subjects will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with urothelial, melanoma or head and neck cancer. Subjects will be seen frequently by the Study Physician after receiving their T cells for the next 6 months. After that, subjects will be seen every 3, 6, or 12 months according to the Schedule of Procedures. All subjects completing or withdrawing from the interventional portion of the study will enter a long term follow-up phase for observation of delayed adverse events and overall survival for 15 years post-infusion.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Melanoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers
  • Official Title: Phase 1 Cell Dose Escalation Study to Assess the Safety and Tolerability of Genetically Engineered MAGE-A10ᶜ⁷⁹⁶T in HLA-A2+ Subjects With MAGE-A10 Positive Urothelial, Melanoma or Head and Neck Tumors

Clinical Trial IDs

  • ORG STUDY ID: ADP-0022-004
  • NCT ID: NCT02989064

Conditions

  • Urothelial Carcinoma
  • Head and Neck Cancer
  • Melanoma
  • Bladder Urothelial Carcinoma

Purpose

This Phase 1 study is designed as a cell dose escalation trial in HLA-A*02:01 and HLA-A*02:06 subjects with MAGE-A10 positive urothelial, melanoma or head and neck tumors. The study will enroll subjects at least 18 years of age using a modified 3+3 cell dose escalation design, to evaluate dose limiting toxicities and determine the target cell dose range. Following the dose escalation phase, additional subjects will be enrolled at the target cell dose range to further characterize safety and the effects at this cell dose. The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. When the MAGE-A10ᶜ⁷⁹⁶T cells are available, subjects will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with urothelial, melanoma or head and neck cancer. Subjects will be seen frequently by the Study Physician after receiving their T cells for the next 6 months. After that, subjects will be seen every 3, 6, or 12 months according to the Schedule of Procedures. All subjects completing or withdrawing from the interventional portion of the study will enter a long term follow-up phase for observation of delayed adverse events and overall survival for 15 years post-infusion.

Trial Arms

NameTypeDescriptionInterventions
Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cellsExperimental

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Subject is ≥18 years of age at the time of signing the study informed consent.
    
              2. Subject has histologically confirmed diagnosis of any one of the following cancers:
                 (A) urothelial cancer (transitional cell cancer of the bladder, ureter or renal
                 pelvis), (B) melanoma, or (C) squamous cell carcinoma of the head and neck.
    
              3. Subject is HLA-A*02:01 and/or HLA-A*02:06 positive.
    
              4. Subject has measurable disease according to RECIST v1.1 criteria prior to
                 lymphodepletion
    
              5. Subject meets disease-specific requirements per protocol
    
              6. Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3
                 months prior to lymphodepletion.
    
            Exclusion Criteria:
    
              1. Subject is HLA-A*02:05 in either allele, HLA-B*15:01 and/or HLA-B*46:01 positive.
                 Subject has any A*02 null allele (designated with an "N", e.g. A*02:32N) as the sole
                 HLA-A*02 allele.
    
              2. Subject is receiving excluded therapy/treatment per protocol
    
              3. Subject has symptomatic CNS metastases.
    
              4. Subject has any other active malignancy besides the tumor under study within 3 years
                 prior to Screening. Subject has uncontrolled intercurrent illness
    
              5. Subject has active infection with HIV, HBV, HCV or HTLV
    
              6. Subject is pregnant or breastfeeding.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of subjects with adverse events (AE), including serious adverse events (SAE).
    Time Frame:3 years
    Safety Issue:
    Description:Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation; and cardiac assessments, including ECG/troponin.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Adaptimmune

    Trial Keywords

    • Cell Therapy
    • T Cell Therapy
    • SPEAR T Cell
    • MAGE-A10
    • Immuno-oncology
    • Metastatic
    • Urothelial Cancer
    • Previously Treated
    • T Cell Receptor
    • Inoperable
    • Advanced
    • Cancer
    • Bladder
    • Head and neck
    • Melanoma

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