Ignite Creation Date:
2025-12-25 @ 4:06 AM
Ignite Modification Date:
2026-03-06 @ 4:46 AM
Study NCT ID:
NCT02770820
Status:
TERMINATED
Last Update Posted:
2021-10-29
First Post:
2016-03-25
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Laboratory-Treated (Central Memory/Naive) CD8+ T Cells in Treating Patients With Newly Diagnosed or Relapsed Acute Myeloid Leukemia
Sponsor:
Fred Hutchinson Cancer Center
Organization:
Study Overview
Official Title:
Phase I/II Study of Autologous (Central Memory/Naïve) 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 I/II trial studies the side effects of laboratory-treated (central memory/naive) cluster of differentiation 8+ T cells (autologous Wilms tumor \[WT\]1-T cell receptor \[TCRc\]4 gene-transduced CD8-positive central memory T-cells \[TCM\]/naive 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 TCM/TN lymphocytes, are taken from a patient's 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 safety/potential 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 (e.g. 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, cytogenetics/fluorescence in situ hybridization (FISH) and/or 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+ TCM/TN 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 safety/potential 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 (e.g. 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, cytogenetics/fluorescence in situ hybridization (FISH) and/or 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+ TCM/TN 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:
True
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2016-00042 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| 9296 | OTHER | Fred Hutch/University of Washington Cancer Consortium | View | |
| P01CA018029 | NIH | None | https://reporter.nih.gov/quic… | View |
| P30CA015704 | NIH | None | https://reporter.nih.gov/quic… | View |
| RG9216011 | OTHER | Fred Hutch/University of Washington Cancer Consortium | View |