Ignite Creation Date:
2024-05-06 @ 12:11 PM
Last Modification Date:
2024-10-26 @ 12:55 PM
Study NCT ID:
NCT03691376
Status:
TERMINATED
Last Update Posted:
2024-03-12
First Post:
2018-09-27
Brief Title:
Genetically Engineered Cells NY-ESO-1 TCR Engineered T Cells and HSCs After Melphalan Conditioning Regimen in Treating Patients With Recurrent or Refractory Ovarian Fallopian Tube or Primary Peritoneal Cancer
Sponsor:
Roswell Park Cancer Institute
Organization:
Roswell Park Cancer Institute
Study Overview
Official Title:
A Phase I Open Label Study Evaluating the Safety and Efficacy of Adoptive Transfer of Autologous NY-ESO-1 CD8-TCR Engineered T Cells and NY-ESO-1 CD4-TCR Engineered Hematopoietic Stem Cells HSC After a Myeloablative Conditioning Regimen With Administration of IL-2 in Patients With Recurrent or Treatment Refractory Ovarian Fallopian Tube or Primary Peritoneal Cancer
Status:
TERMINATED
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Lack of funding
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the best dose and side effects of NY-ESO-1 T cell receptor TCR engineered T cells and how well they work with NY-ESO-1 TCR engineered hematopoietic stem cells HSCs after melphalan conditioning regimen in treating patients with ovarian fallopian tube or primary peritoneal cancer that has come back recurrent or does not respond to treatment refractory The melphalan conditioning chemotherapy makes room in the patients bone marrow for new blood cells and blood-forming cells stem cells to grow Giving NY-ESO-1 TCR T cells and stem cells after the conditioning chemotherapy is intended to replace the immune system with new immune cells that have been redirected to attack and kill the cancer cells and thereby improve immune system function against cancer Giving NY-ESO-1 TCR engineered T cells and HSCs after melphalan may work better in treating patients with ovarian fallopian tube or primary peritoneal cancer
Detailed Description:
PRIMARY OBJECTIVES
I To assess the safety and feasibility of intravenous infusion of autologous peripheral blood mononuclear cells PBMC and CD34 peripheral blood stem cells PBSC that have been genetically modified ex vivo to express NY-ESO-1 TCR following a myeloablative conditioning regimen
Ia Assessment of toxicities using Common Toxicity Criteria CTC and definition of a maximum tolerated dose MTD
SECONDARY OBJECTIVES
I TCR engineered hematopoietic stem cell HSC engraftment II Functional assays for TCR transgenic cells III Progression-free survival PFS compare with the duration of the PFS in the last treatment regimen
IV Durable tumor response in at least 30 of the patients defined as immune-related complete response irCR or immune-related partial response irPR by immune-related Response Evaluation Criteria in Solid Tumors irRECIST criteria at 6 months
V Long-term persistence of TCR transgenic cells regardless of cell origin as evidenced by 5 of CD3 lymphocytes being NY-ESO-1 specific by major histocompatibility complex MHC tetramer assay at 3 and 6 months
VI Discrimination of TCR transgenic cells resulting from retrovirally-transduced mature lymphocytes and lentivirally-transduced HSCs and their phenotyping
VII Long term monitoring for replication competent retrovirus and lentivirus VIII Analysis of viral insertion sites in long term persisting NY-ESO-1 TCR clones absence of a clonal expansion of TCR transgenic cells with a particular transgene insertion site defined as a clone comprising 20 of all PBSC-derived gene-marked cells
IX Gut microbiota pre and post treatment to evaluate the role of microbiota on the therapeutic efficacy of the proposed therapy
OUTLINE This is a dose-escalation study of autologous NY-ESO-1-specific CD8-positive T lymphocytes
Patients receive melphalan intravenously IV over 30 minutes on day -1 Patients then receive autologous NY-ESO-1 CD4-TCR CD34 HSC IV on day 0 and autologous NY-ESO-1-specific CD8-positive T lymphocytes IV between days 7 and 21 Patients also receive aldesleukin subcutaneously SC twice daily BID for 14 days on the following day after the T cell infusion between days 8 and 22
After completion of study treatment patients are followed up every 6 months for 5 years then annually for up to 15 years
I To assess the safety and feasibility of intravenous infusion of autologous peripheral blood mononuclear cells PBMC and CD34 peripheral blood stem cells PBSC that have been genetically modified ex vivo to express NY-ESO-1 TCR following a myeloablative conditioning regimen
Ia Assessment of toxicities using Common Toxicity Criteria CTC and definition of a maximum tolerated dose MTD
SECONDARY OBJECTIVES
I TCR engineered hematopoietic stem cell HSC engraftment II Functional assays for TCR transgenic cells III Progression-free survival PFS compare with the duration of the PFS in the last treatment regimen
IV Durable tumor response in at least 30 of the patients defined as immune-related complete response irCR or immune-related partial response irPR by immune-related Response Evaluation Criteria in Solid Tumors irRECIST criteria at 6 months
V Long-term persistence of TCR transgenic cells regardless of cell origin as evidenced by 5 of CD3 lymphocytes being NY-ESO-1 specific by major histocompatibility complex MHC tetramer assay at 3 and 6 months
VI Discrimination of TCR transgenic cells resulting from retrovirally-transduced mature lymphocytes and lentivirally-transduced HSCs and their phenotyping
VII Long term monitoring for replication competent retrovirus and lentivirus VIII Analysis of viral insertion sites in long term persisting NY-ESO-1 TCR clones absence of a clonal expansion of TCR transgenic cells with a particular transgene insertion site defined as a clone comprising 20 of all PBSC-derived gene-marked cells
IX Gut microbiota pre and post treatment to evaluate the role of microbiota on the therapeutic efficacy of the proposed therapy
OUTLINE This is a dose-escalation study of autologous NY-ESO-1-specific CD8-positive T lymphocytes
Patients receive melphalan intravenously IV over 30 minutes on day -1 Patients then receive autologous NY-ESO-1 CD4-TCR CD34 HSC IV on day 0 and autologous NY-ESO-1-specific CD8-positive T lymphocytes IV between days 7 and 21 Patients also receive aldesleukin subcutaneously SC twice daily BID for 14 days on the following day after the T cell infusion between days 8 and 22
After completion of study treatment patients are followed up every 6 months for 5 years then annually for up to 15 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?:
True
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| i 287616 | OTHER | Roswell Park Cancer Institute | None |
| NCI-2018-01758 | REGISTRY | None | None |