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 between the ages of 18 and 75 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Infusion of autologous genetically modified MAGE A10ᶜ⁷⁹⁶T on Day 1
Massachusetts General Hospital
Boston, Massachusetts, United States
Washington University - School of Medicine
St Louis, Missouri, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Tennessee Oncology - Sarah Cannon Research Institute
Nashville, Tennessee, United States
Vanderbilt - Ingram Cancer Center
Nashville, Tennessee, United States
MD Anderson Cancer Center
Houston, Texas, United States
Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Start Madrid-FJD, Fundación Jimѐnez Díaz
Madrid, Spain
...and 1 more locations
Number of subjects with adverse events (AE), including serious adverse events (SAE).
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.
Time frame: 3 years
Evaluation of the persistence of genetically modified T cells
Evaluation of the persistence of the infused T cells in the periphery.
Time frame: 3 years
Measurement of RCL in genetically modified T cells.
Evaluation of RCL in Subject PBMCs using PCR-based assay.
Time frame: 3 years
Assessment of dose limiting toxicities to determine optimally tolerated dose range
Evaluation of dose limiting toxicities will be performed using the CTCAE Version 4.0
Time frame: 3 years
Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).
Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1
Time frame: 3 years
Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.
Evaluation of the efficacy of the treatment by assessment of time to first response.
Time frame: 3 years
Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.
Evaluation of the efficacy of the treatment by assessment of duration of response.
Time frame: 3 years
Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause.
Evaluation of the efficacy of the treatment by assessment of duration of stable disease.
Time frame: 3 years
Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause
Evaluation of the efficacy of the treatment by assessment of progression-free survival.
Time frame: 3 years
Interval between the date of first T cell infusion and date of death due to any cause.
Evaluation of the efficacy of the treatment by assessment of overall survival.
Time frame: 3 years
Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)
* 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
Time frame: 15 years post last treatment (infusion)
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