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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

November 7, 2016
December 12, 2016
August 20, 2018
October 2016
November 2019   (Final data collection date for primary outcome measure)
  • 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.
  • 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.
  • Measurement of RCL in genetically modified T cells. [ Time Frame: 3 years ]
    Evaluation of RCL in Subject PBMCs using PCR-based assay.
  • 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
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 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, coagulation and anti-MAGE-A10 antibodies; and cardiac assessments, including ECG/troponin.
  • 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.
  • Measurement of RCL in genetically modified T cells. [ Time Frame: 3 years ]
    Evaluation of RCL in Subject PBMCs using PCR-based assay.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Complete list of historical versions of study NCT02989064 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
  • Mean fluorescence intensity (expression) of specific surface markers on gene-modified T cells. [ Time Frame: 3 years ]
    Killing profile and cytokine profile of genetically modified T cells will be evaluated using flow cytometry.
  • Evaluation of MAGE A10 expression pre and post infusion using IHC. [ Time Frame: 3 years ]
    Determine MAGE A10 expression post therapy.
  • Measure polymorphisms in cytokine genes. [ Time Frame: 3 years ]
    Association of polymorphisms with cytokine production.
 
MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers
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

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.

Not Provided
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Urinary Bladder Cancer
  • Head and Neck Cancer
  • Melanoma
Genetic: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
Infusion of autologous genetically modified MAGE A10ᶜ⁷⁹⁶T on Day 1
Experimental: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
Intervention: Genetic: Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
22
Same as current
May 2020
November 2019   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: David Hong, MD 713-563-1930
Canada,   United States
 
 
NCT02989064
ADP-0022-004
Not Provided
Not Provided
Not Provided
Adaptimmune
Adaptimmune
Not Provided
Principal Investigator: David Hong, MD M.D. Anderson Cancer Center
Adaptimmune
August 2018

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