Ignite Creation Date:
2025-12-24 @ 3:56 PM
Ignite Modification Date:
2026-02-25 @ 8:48 PM
Study NCT ID:
NCT02775292
Status:
COMPLETED
Last Update Posted:
2025-07-30
First Post:
2016-05-13
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Gene-Modified T Cells, Vaccine Therapy, and Nivolumab in Treating Patients With Stage IV or Locally Advanced Solid Tumors Expressing NY-ESO-1
Sponsor:
Jonsson Comprehensive Cancer Center
Organization:
Study Overview
Official Title:
NY-ESO-1 TCR Engineered Adoptive Cell Transfer Therapy With Nivolumab PD-1 Blockade
Status:
COMPLETED
Status Verified Date:
2019-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NYM
Brief Summary:
This phase I trial studies the side effects and the best dose of nivolumab when given together with gene-modified T cells and vaccine therapy in treating patients with solid tumors that express the cancer-testes antigen NY-ESO-1 gene AND have spread from where it started to nearby tissue or lymph nodes (locally advanced) or distant organs (stage IV). T cells are a special type of white blood cells (immune cell) that have the ability to kill cancer cells. Nivolumab may block PD-1 which is found on T cells and help the immune system kill cancer cells. Placing a modified gene for the NY-ESO-1 T cell receptor (TCR) 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. Dendritic cells are another type of blood cell that can teach other cells in the body to look for cancer cells and attack them. Giving a dendritic cell vaccine with the NY-ESO-1 protein may help dendritic cells teach the immune system to target cancer cells expressing that protein, and further help the T cells attack cancer. Giving nivolumab together with gene-modified T-cells and dendritic cell vaccine may teach the immune system to recognize and kill cancer cells that express NY-ESO-1.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the safety of the addition of the PD-1 blocking monoclonal antibody, nivolumab, to NY-ESO TCR-transduced autologous peripheral blood lymphocyte (PBL) adoptive cell transfer (ACT) in a dose escalation scheme in two study cohorts at 1 mg/kg and 3 mg/kg of nivolumab intravenous (i.v.) every two weeks for up to 2 years.
SECONDARY OBJECTIVES:
I. To determine the feasibility of delivering the TCR transgenic cell dose and PD-1 blockade to patients.
II. To determine the persistence of NY-ESO-1 TCR-engineered peripheral blood mononuclear cell (PBMC) in serial peripheral blood samples and in biopsies of accessible metastatic lesions.
EXPLORATORY OBJECTIVES:
I. To determine whether blocking PD-1 will maintain the antitumor functionality of adoptively transferred TCR transgenic lymphocytes.
II. To explore the use of positron emission tomography (PET)-based imaging using the PET tracer (18F) fluorodeoxy-glucose (\[18F\]FDG) with the goal of determining if the adoptively transferred NY-ESO-1 TCR-engineered PBMC when administered with nivolumab home and expand in secondary lymphoid organs and tumor deposits.
III. Clinical antitumor activity recording objective response rate.
OUTLINE: This is a dose-escalation study of nivolumab.
CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -5 to -4 and fludarabine phosphate IV over 15-30 minutes on days -4 to -1.
NY-ESO-1 TCR PBMC INFUSION: Patients receive NY-ESO-1 TCR PBMC IV on day 0.
NIVOLUMAB: Patients receive nivolumab IV over 60 minutes on day 0 or 1. Treatment repeats every 2 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
NY-ESO-1(157-165) PEPTIDE PULSED DENDRITIC CELL (DC): Patients receive NY-ESO-1(157-165) peptide pulsed DC intradermally (ID) on days 1, 14, and 28.
LOW DOSE ALDESLEUKIN ADMINISTRATION: Patients receive aldesleukin subcutaneously (SC) twice daily (BID) for 7 days beginning on day 1 for a maximum of 14 doses.
After completion of study treatment, patients are followed up at least every 6 months for 3 years and then at least every 12 months for up to 15 years.
I. To determine the safety of the addition of the PD-1 blocking monoclonal antibody, nivolumab, to NY-ESO TCR-transduced autologous peripheral blood lymphocyte (PBL) adoptive cell transfer (ACT) in a dose escalation scheme in two study cohorts at 1 mg/kg and 3 mg/kg of nivolumab intravenous (i.v.) every two weeks for up to 2 years.
SECONDARY OBJECTIVES:
I. To determine the feasibility of delivering the TCR transgenic cell dose and PD-1 blockade to patients.
II. To determine the persistence of NY-ESO-1 TCR-engineered peripheral blood mononuclear cell (PBMC) in serial peripheral blood samples and in biopsies of accessible metastatic lesions.
EXPLORATORY OBJECTIVES:
I. To determine whether blocking PD-1 will maintain the antitumor functionality of adoptively transferred TCR transgenic lymphocytes.
II. To explore the use of positron emission tomography (PET)-based imaging using the PET tracer (18F) fluorodeoxy-glucose (\[18F\]FDG) with the goal of determining if the adoptively transferred NY-ESO-1 TCR-engineered PBMC when administered with nivolumab home and expand in secondary lymphoid organs and tumor deposits.
III. Clinical antitumor activity recording objective response rate.
OUTLINE: This is a dose-escalation study of nivolumab.
CONDITIONING REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -5 to -4 and fludarabine phosphate IV over 15-30 minutes on days -4 to -1.
NY-ESO-1 TCR PBMC INFUSION: Patients receive NY-ESO-1 TCR PBMC IV on day 0.
NIVOLUMAB: Patients receive nivolumab IV over 60 minutes on day 0 or 1. Treatment repeats every 2 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
NY-ESO-1(157-165) PEPTIDE PULSED DENDRITIC CELL (DC): Patients receive NY-ESO-1(157-165) peptide pulsed DC intradermally (ID) on days 1, 14, and 28.
LOW DOSE ALDESLEUKIN ADMINISTRATION: Patients receive aldesleukin subcutaneously (SC) twice daily (BID) for 7 days beginning on day 1 for a maximum of 14 doses.
After completion of study treatment, patients are followed up at least every 6 months for 3 years and then at least every 12 months for up to 15 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2016-00201 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| R35CA197633 | NIH | None | https://reporter.nih.gov/quic… | View |
| 15-001433 | OTHER | UCLA / Jonsson Comprehensive Cancer Center | View | |
| K12HD000850 | NIH | None | https://reporter.nih.gov/quic… | View |