Phase I/II Study to Assess the Safety and Activity of Enhanced TCR Transduced Autologous T Cells in Metastatic Melanoma
The purpose of this early (phase I/II) clinical trial is to assess the effects (both good and bad) of genetically modified T cells after chemotherapy on your cancer and general health.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study to Assess the Safety and Activity of Enhanced TCR Transduced Autologous T Cells Against Cancer-testis Antigens in Metastatic Melanoma|
- Safety and Tolerability [ Time Frame: Daily monitoring from Day1-Day 16, weekly therafter through week 12, monthly therafter through month 12. ] [ Designated as safety issue: No ]To determine the safety and tolerability of a fixed split-dose of autologous t cells transduced with lentiviral vector encoding an enhanced TCR after non-myeloablative chemotherapy.
- Clinical Activity of TCR gene therapy [ Time Frame: every 4 weeks until month 5 and then every other month through month 11 ] [ Designated as safety issue: No ]To determine the clinical activity TCR gene therapy as assessed by RECIST criteria and progression-free survival.
- Persistence of modified T cells in the peripheral blood [ Time Frame: Days: 1, 5-9, 12-6, then weekly for 10 weeks ] [ Designated as safety issue: No ]To determine the persistence of modified T cells in the peripheral blood and at tumor sites.
- T cell function [ Time Frame: Weeks 4 and 8 post T cell infusion ] [ Designated as safety issue: No ]To determine the functional properties and phenotype of modified T cells from peripheral blood and tumor sites. T cell function is essential to document the activity (or inactivity) of TCR positive T cells isolated from each patient at certain time points after adoptive transfer. We hypothesize that functional TCR positive T cells as assessed by our ex vivo analysis will be associated with clinical response and improved outcomes. In contrast, anergic T cells will be associated with disease progression.
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||February 2030|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
Subject's tumor must express cancer testis antigen NYESO-1 and be HLA-A*02 positive
Cytoreductive chemotherapy followed by infusion with NYESO-1(C259) transduced autologous T cells
Purpose of this study is to evaluate the safety and tolerability of autologous genetically modified T cells. Genetic material is transferred into the subject's previously harvested autologous T cells to redirect them to target melanoma cells rather than their usual target. Study subjects must have histologically or cytologically melanoma stage 3/4 and their tumor must express HLA Class 1 allele HLA-A*0201 for NY-ESO-1/LAGE. Subjects must also have measureable disease on study entry, as defined by at least one lesion that can be measured in at least one dimension >= 10mm with spiral CT scan.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01350401
|United States, Connecticut|
|Yale School of Medicine||Recruiting|
|New Haven, Connecticut, United States, 06520|
|Contact: Harriet Kluger, MD email@example.com|
|United States, Missouri|
|Washington University in St. Louis||Recruiting|
|St. Louis, Missouri, United States, 63110|
|Contact: Gerald P Linette, MD, PhD 314-362-5677|
|Principal Investigator:||Gerald P Linette, MD, PhD||Washington University School of Medicine|
|Principal Investigator:||Harriet Kluger, MD||Yale New Haven Health System Center for Healthcare Solutions|