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.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||May 15, 2017||Phase 1||Interventional|
Primary Outcome 1 - Measure: Number of subjects with adverse events (AE), including serious adverse events (SAEs).
Primary Outcome 1 - Time Frame: 3.5 years
Primary Outcome 2 - Measure: Determining dose limiting toxicities (DLT) and optimally tolerated dose range
Primary Outcome 2 - Time Frame: 3.5 years
Primary Outcome 3 - Measure: Evaluation of persistence of genetically modified T cells.
Primary Outcome 3 - Time Frame: 3.5 years
Primary Outcome 4 - Measure: Measurement of RCL in genetically modified T cells.
Primary Outcome 4 - Time Frame: 3.5 years
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
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
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.
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
Minimum Age: 18 Years
Maximum Age: 75 Years
Healthy Volunteers: No
Name: David Hong, MD
Role: Principal Investigator
Affiliation: M.D. Anderson Cancer Center
Name: David Hong, MD
|University of Miami
Miami, Florida 33136
|Moffitt Cancer Center
Tampa, Florida 33612
|Washington University School of Medicine
Saint Louis, Missouri 63110
|Roswell Park Cancer Institute
Buffalo, New York 14263
Amy Whitworth, BSN
|Duke University Medical Center, Duke Cancer Institute
Durham, North Carolina 27710
Shawna Savage, RN, BSN
|Ohio State University Wexner Medical Center
Columbus, Ohio 43210
|Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111
Anthony Olszanski, MD, RPh
|Tennessee Oncology - Sarah Cannon Research Institute
Nashville, Tennessee 37203
|M.D. Anderson Cancer Center
Houston, Texas 77030
|Princess Margaret Cancer Centre
Toronto, Ontario M5G1X6
Adrian Sacher, MD