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.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||Start Date: October 2016||Phase 1||Interventional|
Primary Outcome 1 - Measure: Number of subjects with adverse events (AE), including serious adverse events (SAE).
Primary Outcome 1 - Time Frame: 3 years
Primary Outcome 2 - Measure: Evaluation of the persistence of genetically modified T cells
Primary Outcome 2 - Time Frame: 3 years
Primary Outcome 3 - Measure: Measurement of RCL in genetically modified T cells.
Primary Outcome 3 - Time Frame: 3 years
Primary Outcome 4 - Measure: Assessment of dose limiting toxicities to determine optimally tolerated dose range
Primary Outcome 4 - Time Frame: 3 years
Primary Outcome 5 - Measure: Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).
Primary Outcome 5 - Time Frame: 3 years
Primary Outcome 6 - Measure: Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.
Primary Outcome 6 - Time Frame: 3 years
Primary Outcome 7 - Measure: Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.
Primary Outcome 7 - Time Frame: 3 years
Primary Outcome 8 - Measure: Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause.
Primary Outcome 8 - Time Frame: 3 years
Primary Outcome 9 - Measure: Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause
Primary Outcome 9 - Time Frame: 3 years
Primary Outcome 10 - Measure: Interval between the date of first T cell infusion and date of death due to any cause.
Primary Outcome 10 - Time Frame: 3 years
Primary Outcome 11 - Measure: Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)
Primary Outcome 11 - Time Frame: 15 years post last treatment (infusion)
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
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.
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
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.
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: David Hong, MD
Role: Principal Investigator
Affiliation: M.D. Anderson Cancer Center
Name: David Hong, MD
|Massachusetts General Hospital
Boston, Massachusetts 02114
Ryan Sullivan, MD
|Fox Chase Cancer Center
Philadelphia, Pennsylvania 19111
|Tennessee Oncology - Sarah Cannon Research Institute
Nashville, Tennessee 37203
|MD Anderson Cancer Center
Houston, Texas 77030
|Princess Margaret Cancer Centre
Toronto, Ontario M5G1X6
Marcus Butler, MD