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

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ClinicalTrials.gov Identifier: NCT02989064
Recruitment Status : Recruiting
First Posted : December 12, 2016
Last Update Posted : August 20, 2018
Sponsor:
Information provided by (Responsible Party):
Adaptimmune

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Urinary Bladder Cancer Head and Neck Cancer Melanoma Genetic: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : October 2016
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : May 2020


Arm Intervention/treatment
Experimental: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells Genetic: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
Infusion of autologous genetically modified MAGE A10ᶜ⁷⁹⁶T on Day 1




Primary Outcome Measures :
  1. Number of subjects with adverse events (AE), including serious adverse events (SAE). [ Time Frame: 3 years ]
    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.

  2. Evaluation of the persistence of genetically modified T cells [ Time Frame: 3 years ]
    Evaluation of the persistence of the infused T cells in the periphery.

  3. Measurement of RCL in genetically modified T cells. [ Time Frame: 3 years ]
    Evaluation of RCL in Subject PBMCs using PCR-based assay.

  4. Assessment of dose limiting toxicities to determine optimally tolerated dose range [ Time Frame: 3 years ]
    Evaluation of dose limiting toxicities will be performed using the CTCAE Version 4.0

  5. Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR). [ Time Frame: 3 years ]
    Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1

  6. Interval between the date of first T cell infusion dose and first documented evidence of CR or PR. [ Time Frame: 3 years ]
    Evaluation of the efficacy of the treatment by assessment of time to first response.

  7. Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause. [ Time Frame: 3 years ]
    Evaluation of the efficacy of the treatment by assessment of duration of response.

  8. Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause. [ Time Frame: 3 years ]
    Evaluation of the efficacy of the treatment by assessment of duration of stable disease.

  9. Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause [ Time Frame: 3 years ]
    Evaluation of the efficacy of the treatment by assessment of progression-free survival.

  10. Interval between the date of first T cell infusion and date of death due to any cause. [ Time Frame: 3 years ]
    Evaluation of the efficacy of the treatment by assessment of overall survival.

  11. Number and % of subjects having any Long Term Follow Up Adverse Events (AEs) [ Time Frame: 15 years post last treatment (infusion) ]
    • New occurrence of any malignancy
    • New occurrence or exacerbation of a pre-existing neurologic disorder
    • New occurrence or exacerbation of a prior rheumatologic or other autoimmune disorder
    • New occurrence of a hematologic disorder
    • New occurrence of any opportunistic and/or serious infections
    • New occurrence of any unanticipated illness and/or hospitalization deemed related to gene modified cell therapy



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT02989064


Contacts
Contact: David Hong, MD 713-563-1930

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Ryan Sullivan, MD    617-724-4000    rsullivan7@partners.org   
Principal Investigator: Ryan Sullivan, MD         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Patti Kelly    215-728-2195    patriciamurphy@fccc.edu   
Principal Investigator: Anthony Olszanski, MD, RPh         
United States, Tennessee
Tennessee Oncology - Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact    615-339-4214    asksarah@sarahcannon.com   
Principal Investigator: Melissa Johnson, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Danxia Ke    713-792-4384    dke@mdanderson.org   
Contact: Ly M Nguyen         
Principal Investigator: David S Hong, MD         
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G1X6
Contact: Marcus Butler, MD    416-946-4501    TIP@uhn.ca   
Contact: Anna Spreafico         
Principal Investigator: Marcus Butler, MD         
Sponsors and Collaborators
Adaptimmune
Investigators
Principal Investigator: David Hong, MD M.D. Anderson Cancer Center

Responsible Party: Adaptimmune
ClinicalTrials.gov Identifier: NCT02989064     History of Changes
Other Study ID Numbers: ADP-0022-004
First Posted: December 12, 2016    Key Record Dates
Last Update Posted: August 20, 2018
Last Verified: August 2018

Keywords provided by Adaptimmune:
Cell Therapy
T Cell Therapy
SPEAR T Cell
MAGE-A10
Immuno-oncology
Metastatic
Urothelial Cancer
Previously Treated
T Cell Receptor

Additional relevant MeSH terms:
Melanoma
Head and Neck Neoplasms
Urinary Bladder Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases