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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 : June 3, 2021
Sponsor:
Information provided by (Responsible Party):
Adaptimmune

Tracking Information
First Submitted Date  ICMJE April 25, 2017
First Posted Date  ICMJE April 28, 2017
Last Update Posted Date June 3, 2021
Actual Study Start Date  ICMJE July 5, 2017
Estimated Primary Completion Date September 2032   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2018)
  • 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.
  • Determining dose limiting toxicities (DLT) and optimally tolerated dose range [ Time Frame: 3.5 years ]
    Evaluate DLTs and toxicity assessment using NCI CTCAE.
  • Evaluation of persistence of genetically modified T cells. [ Time Frame: 3.5 years ]
    Evaluation of persistence of genetically modified T cells in the periphery.
  • Measurement of RCL in genetically modified T cells. [ Time Frame: 3.5 years ]
    Evaluation of RCL in subject PBMCs using PCR-based assay.
Original Primary Outcome Measures  ICMJE
 (submitted: April 25, 2017)
  • 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, coagulation, and anti-MAGE-A4 TCR antibodies.
  • Determining dose limiting toxicities (DLT) and optimally tolerated dose range [ Time Frame: 3.5 years ]
    Evaluate DLTs and toxicity assessment using NCI CTCAE.
  • Evaluation of persistence of genetically modified T cells. [ Time Frame: 3.5 years ]
    Evaluation of persistence of genetically modified T cells in the periphery.
  • Measurement of RCL in genetically modified T cells. [ Time Frame: 3.5 years ]
    Evaluation of RCL in subject PBMCs using PCR-based assay.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2019)
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2017)
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Current Other Pre-specified Outcome Measures
 (submitted: June 18, 2020)
MAGE-A4c1032T cell trafficking in tumor lesion(s). [ Time Frame: 3.5 years ]
Evaluation of post-infusion T-cell trafficking in irradiated vs non-irradiation lesions
Original Other Pre-specified Outcome Measures
 (submitted: April 25, 2017)
  • Mean fluorescence intensity (expression) of specific surface markers on gene-modified T cells in blood and tumor. [ Time Frame: 3.5 years ]
    Killing profile and cytokine profile of genetically modified T cells will be evaluated using flow cytometry in blood and tumor.
  • Measure polymorphisms in cytokine genes. [ Time Frame: 3.5 years ]
    Association of polymorphisms with cytokine production.
 
Descriptive Information
Brief Title  ICMJE MAGE-A4ᶜ¹º³²T for Multi-Tumor
Official Title  ICMJE 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
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. This study has a substudy component that will investigate the safety and tolerability of MAGE-A4c1032T cell therapy in combination with low dose radiation in up to 10 subjects.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
  • Gastroesophageal Junction
Intervention  ICMJE
  • Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
    Infusion of autologous genetically modified MAGE-A4ᶜ¹º³²T on Day 1
  • Radiation: Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation
    Up to 10 subjects will be considered for Radiation sub-study. Radiation with an intensity of 1.4Gy for 5 days before infusion of MAGE-A4c1032T cells
Study Arms  ICMJE
  • Experimental: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
    Intervention: Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
  • Experimental: Radiation Sub-Study: Autologous genetically modified MAGE-A4c1
    Intervention: Radiation: Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation
Publications * Sanderson JP, Crowley DJ, Wiedermann GE, Quinn LL, Crossland KL, Tunbridge HM, Cornforth TV, Barnes CS, Ahmed T, Howe K, Saini M, Abbott RJ, Anderson VE, Tavano B, Maroto M, Gerry AB. Preclinical evaluation of an affinity-enhanced MAGE-A4-specific T-cell receptor for adoptive T-cell therapy. Oncoimmunology. 2019 Nov 24;9(1):1682381. doi: 10.1080/2162402X.2019.1682381. eCollection 2020.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 18, 2020)
52
Original Estimated Enrollment  ICMJE
 (submitted: April 25, 2017)
32
Estimated Study Completion Date  ICMJE September 2035
Estimated Primary Completion Date September 2032   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 indicated tumor types
  3. Subject is HLA-A*02 positive. (This determination will be made under screening protocol ADP-0000-001).
  4. Subject's tumor shows expression of the MAGE-A4 RNA or protein. (This determination will be made under screening protocol ADP-0000-001).
  5. Adequate organ function as indicated in the study protocol
  6. Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion
  7. Subject meets disease-specific requirements per protocol

7. Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months prior to lymphodepletion.

Exclusion Criteria:

  1. Subject does not express appropriate HLA-A genotype
  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.

Additional Exclusion Criteria for the Radiation Substudy:

  • Subject does not meet eligibility criteria for the main study (ADP-0044-001).
  • Subject does not have at least one target lesion amenable to radiation.
  • Certain radiation therapy within 6 months of clinical trial are an exclusion.
  • Metastatic disease impinging on the spinal cord or threatening spinal cord compression.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: David Hong, MD 713-563-5844 dshong@madanderson.org
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03132922
Other Study ID Numbers  ICMJE ADP-0044-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Adaptimmune
Study Sponsor  ICMJE Adaptimmune
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: David Hong, MD M.D. Anderson Cancer Center
PRS Account Adaptimmune
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP