Ignite Creation Date:
2024-05-06 @ 8:34 AM
Last Modification Date:
2024-10-26 @ 12:02 PM
Study NCT ID:
NCT02770820
Status:
TERMINATED
Last Update Posted:
2021-10-29
First Post:
2016-03-25
Brief Title:
Laboratory-Treated Central MemoryNaive CD8 T Cells in Treating Patients With Newly Diagnosed or Relapsed Acute Myeloid Leukemia
Sponsor:
Fred Hutchinson Cancer Center
Organization:
Fred Hutchinson Cancer Center
Study Overview
Official Title:
Phase III Study of Autologous Central MemoryNaïve CD8 T Cells That Have Been Transduced to Express a WT1-Specific T Cell Receptor for Treatment of AML
Status:
TERMINATED
Status Verified Date:
2021-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Terminated due to funding difficulties
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 of laboratory-treated central memorynaive cluster of differentiation 8 T cells autologous Wilms tumor WT1-T cell receptor TCRc4 gene-transduced CD8-positive central memory T-cells TCMnaive T cells TN lymphocytes and how well it works in treating patients with acute myeloid leukemia that is newly diagnosed or has come back Genetically modified therapies such as autologous WT1-TCRc4 gene-transduced CD8-positive TCMTN lymphocytes are taken from a patients blood modified in the laboratory so they specifically may kill cancer cells with a protein called WT1 and safely given back to the patient The genetically modified T-cells have genes added in the laboratory to allow them to recognize leukemia cells that express WT1 and kill them
Detailed Description:
PRIMARY OBJECTIVES
I Determine the safetypotential toxicities associated with treating high-risk acute myeloid leukemia AML patients with autologous CD8 T cells polyclonal Tn and Tcm cells Epstein-Barr virus-specific T cells Tebv cells that have been genetically-modified to express a high affinity WT1-specific TCR TCRC4
II Determine the feasibility of reproducibly treating high-risk AML patients with autologous CD8 T cells polyclonal TN and TCM cells Tebv cells that have been genetically-modified to express a high affinity WT1-specific TCR TCRC4
III Determine and compare the in vivo persistence in blood and at the primary tumor site eg bone marrow chloroma of transferred autologous CD8 T cells polyclonal TN and TCM cells TEBV cells that have been genetically-modified to express a high affinity WT1-specific TCR TCRC4
EXPLORATORY OBJECTIVES
I Determine whether adoptively transferred autologous TCRC4-transduced CD8 cells have anti-tumor activity in patients with acute myeloid leukemia
Ia In patients with measurable minimal residual disease MRD at the time of infusion of TCRC4-transduced CD8 cells changes in leukemic tumor burden will be measured by morphology flow cytometry cytogeneticsfluorescence in situ hybridization FISH andor molecular testing at baseline and after infusion of T cells
Ib In all patients those with or without measurable tumor burden prior to T cell transfer including patients who convert to MRD-negative status during consolidation the probability of relapse disease-free survival and overall survival of patients receiving TCRC4-transduced CD8 cells will be compared with patients in the observation arm
II Determine and compare the migration to the primary tumor site of subsets of the adoptively transferred autologous TCRC4-transduced CD8 T cells polyclonal TN and TCM cells TEBV cells
III Determine and compare the in vivo functional capacity of transferred polyclonal autologous TCRC4-transduced CD8 TCM TN cells and TEBV CD8 cells
OUTLINE
Beginning 4 weeks after completion of last course of consolidation chemotherapy patients receive autologous WT1-TCRc4 gene-transduced CD8 TCMTN lymphocytes intravenously IV over 1-4 hours on day 0 and again after a minimum of 3 weeks Beginning 6 hours after the second infusion of T cells patients also receive aldesleukin subcutaneously SC twice daily BID for 14 days in the absence of disease progression or unacceptable toxicity Patients who have clinically benefitted from T cell therapy may receive additional infusions of T cells and aldesleukin at the discretion of the principal investigator PI and the attending physician
After completion of study treatment patients are followed up weekly for 4 weeks at 2 3 6 and 12 months and then annually for 14 years thereafter
I Determine the safetypotential toxicities associated with treating high-risk acute myeloid leukemia AML patients with autologous CD8 T cells polyclonal Tn and Tcm cells Epstein-Barr virus-specific T cells Tebv cells that have been genetically-modified to express a high affinity WT1-specific TCR TCRC4
II Determine the feasibility of reproducibly treating high-risk AML patients with autologous CD8 T cells polyclonal TN and TCM cells Tebv cells that have been genetically-modified to express a high affinity WT1-specific TCR TCRC4
III Determine and compare the in vivo persistence in blood and at the primary tumor site eg bone marrow chloroma of transferred autologous CD8 T cells polyclonal TN and TCM cells TEBV cells that have been genetically-modified to express a high affinity WT1-specific TCR TCRC4
EXPLORATORY OBJECTIVES
I Determine whether adoptively transferred autologous TCRC4-transduced CD8 cells have anti-tumor activity in patients with acute myeloid leukemia
Ia In patients with measurable minimal residual disease MRD at the time of infusion of TCRC4-transduced CD8 cells changes in leukemic tumor burden will be measured by morphology flow cytometry cytogeneticsfluorescence in situ hybridization FISH andor molecular testing at baseline and after infusion of T cells
Ib In all patients those with or without measurable tumor burden prior to T cell transfer including patients who convert to MRD-negative status during consolidation the probability of relapse disease-free survival and overall survival of patients receiving TCRC4-transduced CD8 cells will be compared with patients in the observation arm
II Determine and compare the migration to the primary tumor site of subsets of the adoptively transferred autologous TCRC4-transduced CD8 T cells polyclonal TN and TCM cells TEBV cells
III Determine and compare the in vivo functional capacity of transferred polyclonal autologous TCRC4-transduced CD8 TCM TN cells and TEBV CD8 cells
OUTLINE
Beginning 4 weeks after completion of last course of consolidation chemotherapy patients receive autologous WT1-TCRc4 gene-transduced CD8 TCMTN lymphocytes intravenously IV over 1-4 hours on day 0 and again after a minimum of 3 weeks Beginning 6 hours after the second infusion of T cells patients also receive aldesleukin subcutaneously SC twice daily BID for 14 days in the absence of disease progression or unacceptable toxicity Patients who have clinically benefitted from T cell therapy may receive additional infusions of T cells and aldesleukin at the discretion of the principal investigator PI and the attending physician
After completion of study treatment patients are followed up weekly for 4 weeks at 2 3 6 and 12 months and then annually for 14 years thereafter
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 |
|---|---|---|---|
| RG9216011 | OTHER | Fred HutchUniversity of Washington Cancer Consortium | httpsreporternihgovquickSearchP30CA015704 |
| 9296 | OTHER | None | None |
| P30CA015704 | NIH | None | None |
| NCI-2016-00042 | REGISTRY | None | None |
| P01CA018029 | NIH | None | None |