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MAGE-A4ᶜ¹º³²T for Multi-Tumor

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ClinicalTrials.gov Identifier: NCT03132922
Recruitment Status : Recruiting
First Posted : April 28, 2017
Last Update Posted : August 9, 2019
Sponsor:
Information provided by (Responsible Party):
Adaptimmune

Brief Summary:
This study will investigate the safety and tolerability of MAGE-A4ᶜ¹º³²T cell therapy in subjects who have the appropriate HLA-A2 tissue marker and whose urinary bladder, melanoma, head and neck, ovarian, non-small cell lung, esophageal, gastric, synovial sarcoma, or myxoid/round call liposarcoma (MRCLS) tumor has the MAGE-A4 protein expressed. This study will take a subject's T cells and give them a T cell receptor protein that recognizes and attacks the tumors.

Condition or disease Intervention/treatment Phase
Urinary Bladder Cancer Melanoma Head and Neck Cancer Ovarian Cancer Non-Small Cell Lung Cancer Esophageal Cancer Gastric Cancer Synovial Sarcoma Myxoid Round Cell Liposarcoma Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Dose Escalation, Multi-tumor Study to Assess the Safety, Tolerability and Antitumor Activity of Genetically Engineered MAGE-A4ᶜ¹º³²T in HLA-A2+ Subjects With MAGE-A4 Positive Tumors
Actual Study Start Date : May 15, 2017
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2035


Arm Intervention/treatment
Experimental: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
Infusion of autologous genetically modified MAGE-A4ᶜ¹º³²T on Day 1




Primary Outcome Measures :
  1. Number of subjects with adverse events (AE), including serious adverse events (SAEs). [ Time Frame: 3.5 years ]
    Determine if treatment with autologous genetically modified T cells (MAGE-A4ᶜ¹º³²T) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation.

  2. Determining dose limiting toxicities (DLT) and optimally tolerated dose range [ Time Frame: 3.5 years ]
    Evaluate DLTs and toxicity assessment using NCI CTCAE.

  3. Evaluation of persistence of genetically modified T cells. [ Time Frame: 3.5 years ]
    Evaluation of persistence of genetically modified T cells in the periphery.

  4. Measurement of RCL in genetically modified T cells. [ Time Frame: 3.5 years ]
    Evaluation of RCL in subject PBMCs using PCR-based assay.


Secondary Outcome Measures :
  1. Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR). [ Time Frame: 3.5 years ]
    Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1

  2. Interval between the date of first T cell infusion dose and first documented evidence of CR or PR. [ Time Frame: 3.5 years ]
    Evaluation of the efficacy of the treatment by assessment of time to first response.

  3. 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: 3.5 years ]
    Evaluation of the efficacy of the treatment by assessment of duration of response.

  4. Interval between the date of first documented evidence of stable disease (SD) until first documented disease progression or death due to any cause. [ Time Frame: 3.5 years ]
    Evaluation of the efficacy of the treatment by assessment of duration of stable disease.

  5. Interval between the date of first T cell infusion and the earliest date of disease, progression or death due to any cause [ Time Frame: 3.5 years ]
    Evaluation of the efficacy of the treatment by assessment of progression-free survival.

  6. Interval between the date of first T cell infusion and date of death due to any cause. [ Time Frame: 3.5 years ]
    Evaluation of the efficacy of the treatment by assessment of overall survival.

  7. 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



Information from the National Library of Medicine

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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: urothelial cancer (transitional cell cancer of the bladder, ureter, urethra or renal pelvis), melanoma, squamous cell carcinoma of the head and neck, ovarian cancer, NSCLC (squamous, adenosquamous, adenocarcinoma or large cell), esophageal (squamous and adenocarcinoma) or gastric cancer, synovial sarcoma or MRCLS.
  3. Subject is HLA-A*02 positive and subject's tumor shows expression of the MAGE-A4 RNA or protein.
  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 positive in either allele; Subject has HLA-A*02:07 as the sole HLA-A*02 allele (e.g., a subject with HLA alleles A*02:04 and A*02:07 is eligible); or 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): NCT03132922


Locations
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United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Michelle Liendo    305-243-0864    mliendo@med.miami.edu   
Contact: Michelle Munevar         
Principal Investigator: Brian Slomovitz, MD         
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Matt Taddeo    817-745-1346    Matt.Taddeo@moffitt.org)   
Contact: Rachel Soto    813-745-4608    Rachel.Soto@moffitt.org   
Principal Investigator: Michaele Druta, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Michelle Landeau    314-747-7997    landeaum@wustl.edu   
Contact: Cheryl Callahan         
Principal Investigator: Brian Van Tine, M.D.         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Amy Whitworth, BSN    716-845-8409    Amy.Whitworth@roswellpark.org   
Contact: Dawn DePaolo         
Principal Investigator: Kunle Odunsi, MD, PhD         
United States, North Carolina
Duke University Medical Center, Duke Cancer Institute Recruiting
Durham, North Carolina, United States, 27710
Contact: Shawna Savage, RN, BSN    919-668-1462    shawna.savage@duke.edu   
Principal Investigator: Jeffrey M Clarke, MD         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Anthony Olszanski, MD, RPh       Anthony.Olszanski@FCCC.edu   
Principal Investigator: Anthony Olszanski, MD, RPh         
United States, Tennessee
Tennessee Oncology - Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Matt Walker    615-339-4214    asksarah@sarahcannon.com   
Principal Investigator: Melissa Johnson, MD         
United States, Texas
M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Danxia Ke    713-792-4384    dke@mdanderson.org   
Principal Investigator: David Hong, MD         
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G1X6
Contact: Adrian Sacher, MD    416-946-4501 ext 5485    TIP@uhn.ca   
Principal Investigator: Adrian Sacher, MD         
Sponsors and Collaborators
Adaptimmune

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Responsible Party: Adaptimmune
ClinicalTrials.gov Identifier: NCT03132922     History of Changes
Other Study ID Numbers: ADP-0044-001
First Posted: April 28, 2017    Key Record Dates
Last Update Posted: August 9, 2019
Last Verified: August 2019

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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 Adaptimmune:
Cell Therapy
T Cell Therapy
SPEAR T Cell
MAGE-A4
Immuno-oncology
Metastatic
Urothelial Cancer
Previously Treated
T Cell Receptor
Squamous, adenosquamous, adenocarcinoma or large cell NSCLC
Squamous or adenocarcinoma esophageal cancer
Sarcoma
Melanoma
Bladder
Ovarian
Additional relevant MeSH terms:
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Melanoma
Sarcoma
Urinary Bladder Neoplasms
Esophageal Neoplasms
Liposarcoma
Sarcoma, Synovial
Liposarcoma, Myxoid
Neoplasms by Site
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Connective and Soft Tissue
Urogenital Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Head and Neck Neoplasms
Urologic Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Esophageal Diseases
Neoplasms, Adipose Tissue
Neoplasms, Connective Tissue