Ignite Creation Date:
2024-05-06 @ 3:55 AM
Last Modification Date:
2024-10-26 @ 11:41 AM
Study NCT ID:
NCT02408016
Status:
TERMINATED
Last Update Posted:
2021-09-13
First Post:
2015-03-31
Brief Title:
Genetically Modified T Cells in Treating Patients With Stage III-IV Non-small Cell Lung Cancer or Mesothelioma
Sponsor:
Fred Hutchinson Cancer Center
Organization:
Fred Hutchinson Cancer Center
Study Overview
Official Title:
Phase III Study in WT1-Expressing Non-small Cell Lung Cancer and Mesothelioma Comparing Cellular Adoptive Immunotherapy With Polyclonal Autologous Central Memory to Naïve CD8 T Cells That Have Been Transduced to Express a WT1-Specific T-Cell Receptor
Status:
TERMINATED
Status Verified Date:
2021-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Terminated due to loss of funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase III trial studies the side effects and best dose of genetically modified T cells in treating patients with stage III-IV non-small cell lung cancer NSCLC or mesothelioma Many types of cancer cells including NSCLC and mesothelioma but not most normal cells have a protein called Wilms tumor WT1 on their surfaces This study takes a type of immune cell from patients called T cells and modifies their genes in the laboratory so that they are programmed to find cells with WT1 and kill them The T cells are then given back to the patient Cyclophosphamide and aldesleukin may also stimulate the immune system to attack cancer cells Giving cyclophosphamide and aldesleukin with laboratory-treated T cells may help the body build an immune response to kill tumor cells
Detailed Description:
PRIMARY OBJECTIVES
I Determine the safety and potential toxicities associated with treating patients with metastatic NSCLC and mesothelioma with polyclonal autologous central memory and naive cluster of differentiation CD8 T cells that have been transduced to express a WT1-specific T-cell receptor TCR Arm 1 and Arm 2
II Determine the feasibility of treating patients with metastatic NSCLC and mesothelioma with polyclonal autologous central memory and naive CD8 T cells that have been transduced to express a WT1-specific TCR Arm 1 and Arm 2
III Determine and compare the in vivo persistence in blood and tumor of transferred polyclonal autologous central memory and naive CD8 T cells that have been transduced to express a WT1-specific TCR Arm 1 and Arm 2
EXPLORATORY OBJECTIVES
I Determine the antitumor efficacy for patients with metastatic NSCLC and mesothelioma Arm 1 as measured by time to progression TTP based on the Response Evaluation Criteria in Solid Tumors RECIST 11 criteria
II Determine the in vivo functional capacity of adoptively transferred polyclonal autologous CD8 T cells that have been transduced to express a WT1-specific TCR and assess the acquisition of phenotypic characteristics associated with T cell exhaustion Arm 1 and Arm 2
III Determine the migration to tumor sites of adoptively transferred polyclonal autologous CD8 T cells that have been transduced to express a WT1-specific TCR Arm 2
IV Evaluate the tumor response and T cell infiltration in tumors of patients with stage IIIA NSCLC treated in the neo-adjuvant setting
OUTLINE This is a phase I dose-escalation study of autologous WT1-TCRc4 gene-transduced CD8-positive TcmTn lymphocytes followed by a phase II study Patients are assigned to 1 of 3 treatment arms
ARM I STAGE I Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive TcmTn lymphocytes intravenously IV on days 0 and 14 cyclophosphamide IV on days 11 and 12 and aldesleukin IL-2 subcutaneously SC twice daily BID for 14 days Patients who have received radiation to the chestlung tissue may receive T lymphocytes 90 days after completion of radiation
ARM I STAGE II Patients receive cyclophosphamide IV on days -3 and -2 autologous WT1-TCRc4 gene-transduced CD8-positive TcmTn lymphocytes IV on day 0 and aldesleukin SC BID for 14 days
ARM II Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive TcmTn lymphocytes IV between 24-96 hours after the last dose of chemotherapy and receive aldesleukin SC BID for 14 days Patients then undergo surgery within 3-4 weeks after the T-cell infusion
After completion of study treatment patients are followed up at 3 6 and 12 months and then annually for 14 years
I Determine the safety and potential toxicities associated with treating patients with metastatic NSCLC and mesothelioma with polyclonal autologous central memory and naive cluster of differentiation CD8 T cells that have been transduced to express a WT1-specific T-cell receptor TCR Arm 1 and Arm 2
II Determine the feasibility of treating patients with metastatic NSCLC and mesothelioma with polyclonal autologous central memory and naive CD8 T cells that have been transduced to express a WT1-specific TCR Arm 1 and Arm 2
III Determine and compare the in vivo persistence in blood and tumor of transferred polyclonal autologous central memory and naive CD8 T cells that have been transduced to express a WT1-specific TCR Arm 1 and Arm 2
EXPLORATORY OBJECTIVES
I Determine the antitumor efficacy for patients with metastatic NSCLC and mesothelioma Arm 1 as measured by time to progression TTP based on the Response Evaluation Criteria in Solid Tumors RECIST 11 criteria
II Determine the in vivo functional capacity of adoptively transferred polyclonal autologous CD8 T cells that have been transduced to express a WT1-specific TCR and assess the acquisition of phenotypic characteristics associated with T cell exhaustion Arm 1 and Arm 2
III Determine the migration to tumor sites of adoptively transferred polyclonal autologous CD8 T cells that have been transduced to express a WT1-specific TCR Arm 2
IV Evaluate the tumor response and T cell infiltration in tumors of patients with stage IIIA NSCLC treated in the neo-adjuvant setting
OUTLINE This is a phase I dose-escalation study of autologous WT1-TCRc4 gene-transduced CD8-positive TcmTn lymphocytes followed by a phase II study Patients are assigned to 1 of 3 treatment arms
ARM I STAGE I Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive TcmTn lymphocytes intravenously IV on days 0 and 14 cyclophosphamide IV on days 11 and 12 and aldesleukin IL-2 subcutaneously SC twice daily BID for 14 days Patients who have received radiation to the chestlung tissue may receive T lymphocytes 90 days after completion of radiation
ARM I STAGE II Patients receive cyclophosphamide IV on days -3 and -2 autologous WT1-TCRc4 gene-transduced CD8-positive TcmTn lymphocytes IV on day 0 and aldesleukin SC BID for 14 days
ARM II Patients receive autologous WT1-TCRc4 gene-transduced CD8-positive TcmTn lymphocytes IV between 24-96 hours after the last dose of chemotherapy and receive aldesleukin SC BID for 14 days Patients then undergo surgery within 3-4 weeks after the T-cell infusion
After completion of study treatment patients are followed up at 3 6 and 12 months and then annually for 14 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2015-00329 | REGISTRY | None | None |
| 2727 | None | None | None |
| 272700 | OTHER | None | None |
| P30CA015704 | NIH | Fred HutchUniversity of Washington Cancer Consortium | httpsreporternihgovquickSearchP30CA015704 |