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Active Not RecruitingNCT02650986

Gene-Modified T Cells With or Without Decitabine in Treating Patients With Advanced Malignancies Expressing NY-ESO-1

A Phase I/IIa Study of TGFß Blockade in TCR-Engineered T-Cell Cancer Immunotherapy in Patients With Advanced Malignancies

Status
Active Not Recruiting
Phase
Phase 1 / Phase 2
Study type
Interventional
Enrollment
15 (actual)
Sponsor
Roswell Park Cancer Institute · Academic / Other
Sex
All
Age
12 Years
Healthy volunteers
Not accepted

Summary

This phase I/IIa trial studies the side effects and best dose of gene-modified T cells when given with or without decitabine, and to see how well they work in treating patients with malignancies expressing cancer-testis antigens 1 (NY-ESO-1) gene that have spread to other places in the body (advanced). A T cell is a type of immune cell that can recognize and kill abnormal cells of the body. Placing a modified gene for NY-ESO-1 into the patients' T cells in the laboratory and then giving them back to the patient may help the body build an immune response to kill tumor cells that express NY-ESO-1. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving gene-modified T cells with or without decitabine works better in treating patients with malignancies expressing NY-ESO-1.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the safety and feasibility of adoptive transfer of TGFbDNRII-transduced autologous tumor infiltrating lymphocytes (autologous NY-ESO-1 TCR/dnTGFbetaRII transgenic T cells). SECONDARY OBJECTIVES: I. NY-ESO-1 TCR/ dnTGFbetaRII 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. To test the hypothesis that NY-ESO-1 TCR/dnTGFbetaRII will constitute in cells more efficient in inducing tumor regression. IV. Determine objective tumor responses by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1. EXPLORATORY OBJECTIVE: I. To evaluate the role of microbiota on the therapeutic efficacy of the proposed therapy. OUTLINE: This is a phase I, dose-escalation study of NY-ESO-1 TCR/TGFbDNRII-transduced TILs followed by a phase IIa study. Participants are assigned 1 to 2 cohorts. COHORT I: Patients undergo leukapheresis on day -6, and receive cyclophosphamide intravenously (IV) over 2 hours on days -5 and -4. Patients then receive TGFbDNRII-transduced autologous tumor infiltrating lymphocytes IV over 15 minutes on day 0. Eligible patients who showed initial response/disease control, may receive a second TGFbDNRII-transduced autologous tumor infiltrating lymphocytes infusion at any time after progression is confirmed. COHORT II: Patients undergo leukapheresis on day -6 and receive decitabine IV over 1 hour on days -6 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients then receive TGFbDNRII-transduced autologous tumor infiltrating lymphocytes IV over 15 minutes on day 0. Eligible patients who showed initial response/disease control, may receive a second TGFbDNRII-transduced autologous tumor infiltrating lymphocytes infusion at any time after progression is confirmed. After completion of study treatment, patients are followed up at weeks 1-4, 6, 8, and 12, at 6 and 9 months, every 6 months for 5 years, and then yearly for 10 years.

Conditions

Interventions

TypeNameDescription
DRUGCyclophosphamideGiven IV
DRUGDecitabineGiven IV
OTHERLaboratory Biomarker AnalysisCorrelative studies
PROCEDURELeukapheresisUndergo leukapheresis
BIOLOGICALTGFbDNRII-transduced Autologous Tumor Infiltrating LymphocytesGiven IV

Timeline

Start date
2017-07-14
Primary completion
2021-03-04
Completion
2032-07-14
First posted
2016-01-08
Last updated
2025-06-17
Results posted
2022-05-31

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT02650986. Inclusion in this directory is not an endorsement.