Gene-Modified T Cells in Treating Patients With Locally Advanced or Stage IV Solid Tumors Expressing NY-ES0-1
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|ClinicalTrials.gov Identifier: NCT02650986|
Recruitment Status : Recruiting
First Posted : January 8, 2016
Last Update Posted : November 15, 2018
|Condition or disease||Intervention/treatment||Phase|
|Adult Solid Neoplasm||Drug: Cyclophosphamide Other: Laboratory Biomarker Analysis Biological: NY-ESO-1 Reactive TCR Retroviral Vector Transduced Autologous PBL Biological: TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes||Phase 1 Phase 2|
I. To evaluate the safety and feasibility of adoptive transfer of autologous NY-ESO-1 T cell receptor (TCR) (NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL)/dominant-negative transforming growth factor-beta receptor II (dnTGFbetaRII) (TGFbDNRII-transduced autologous tumor infiltrating lymphocytes [TILs]) transgenic T cells in combination with Decitabine.
I. NY-ESO-1 TCR/ dnTGFβRII transgenic T cell persistence by analyzing serial peripheral blood samples for the presence of T cells with the NY-ESO-1 TCR by tetramer analysis.
II. To study T cell differentiation that correlates with higher anti-tumor responses.
III. Assess clinical response and progression free survival.
OUTLINE: This is a phase I, dose-escalation study of NY-ESO-1 TCR/TGFbDNRII-transduced TILs followed by a phase II study.
Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -5 and -4. Patients then receive NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL with TGFbDNRII-transduced autologous TILs infusion on day 0.
After completion of study treatment, patients are follow up at weeks 1-4, 8 and 12, at 6 and 9 months, every 6 months for 5 years, and yearly for 9 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/IIa Study of TGFß Blockade in TCR-Engineered T-Cell Cancer Immunotherapy in Patients With Advanced Malignancies|
|Actual Study Start Date :||June 30, 2017|
|Estimated Primary Completion Date :||December 20, 2018|
|Estimated Study Completion Date :||December 20, 2019|
Experimental: Treatment (cyclophosphamide, of NY-ESO-1 TCR/dnTGFbetaRII)
Patients receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients then receive NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL with TGFbDNRII-transduced autologous TILs infusion on day 0.
Other: Laboratory Biomarker Analysis
Biological: NY-ESO-1 Reactive TCR Retroviral Vector Transduced Autologous PBL
Other Name: Anti-NY-ESO-1 TCR Retroviral Vector Transduced Autologous PBL
Biological: TGFbDNRII-transduced Autologous Tumor Infiltrating Lymphocytes
Other Name: TGFbDNRII-transduced Autologous TILs
- Dose-limiting toxicity using Common Toxicity Criteria [ Time Frame: Up to 30 days ]Patients will be monitored by medical histories, physical examinations, ophthalmologic exams, and blood studies to detect potential toxicities from the treatment.
- Feasibility based on potential problems in the manufacturing of NY-ESO-1/ dnTGFβRII engineered cells [ Time Frame: 1 month ]Sufficient numbers of circulating, lot released confirmed T cells will be measured prior to administration.
- Expression of the NY-ESO-1 TCR transgenic protein in peripheral blood mononuclear cells (PBMC) [ Time Frame: Up to 15 years ]TCR and vector presence will be quantitated in PBMC samples, obtained before adoptive transfer and at weeks 1, 2, 4, 8, and 12 after transgenic cell adoptive transfer. Thereafter, sampling will be every 3 months during the first year, and then every 6 to 12 months per schedule of procedures and observations.
- Replication competent retrovirus (RCR) [ Time Frame: Up to 1 year ]
- Tumor response (complete and partial response) as determined by RECIST 1.1 [ Time Frame: UP to 90 days after TCR transgenic PBMC adoptive transfer ]Response assessment will be performed by comparing standard computed tomography imaging scans and photographs of target lesions from baseline.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02650986
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Roswell Park 877-275-7724 ASKRPCI@roswellpark.org|
|Principal Investigator: Richard Koya|
|Principal Investigator:||Richard Koya, MD||Roswell Park Cancer Institute|