Ignite Creation Date:
2024-07-17 @ 10:41 AM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06483048
Status:
RECRUITING
Last Update Posted:
2024-07-09
First Post:
2024-06-25
Brief Title:
MUC1-Activated T Cells for the Treatment of Relapsed and Resistant Ovarian Cancer
Sponsor:
Mayo Clinic
Organization:
Mayo Clinic
Study Overview
Official Title:
Phase 1 Clinical Trial Using Autologous MUC1-Activated T Cells Expanded from Peripheral Blood in Patients with Relapsed and Resistant Ovarian Cancer
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
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 tests the safety side effects best dose of MUC1-activated T cells in treating patients with ovarian cancer that has come back after a period of improvement relapsed or that remains despite treatment resistant T cells are infection fighting blood cells that can kill tumor cells The T cells given in this study will come from the patient and are made in a laboratory to recognize MUC1 a protein on the surface of tumor cells that plays a key role in tumor cell growth These MUC1-activated T cells may help the bodys immune system identify and kill MUC1 expressing ovarian tumor cells
Detailed Description:
PRIMARY OBJECTIVE
I To determine the maximum tolerated dose MTD of autologous MUC1-activated T-cells in-house manufactured MUC1-activated T cells in patients with relapsedrefractory MUC1-expressing ovarian cancer
SECONDARY OBJECTIVES
I Obtain preliminary efficacy associated with MUC1-targeting peripheral blood mononuclear cells PBMC-derived T cells in conjunction with cyclophosphamide CTX in MUC1-expressing ovarian cancer patients as measured by objective response rate best overall response of either partial response PR or complete response CR duration of response clinical benefit rate CR PR or stable disease SD time to disease progression progression free survival PFS and overall survival OS
II Determine feasibility of in-house production and administration of MUC1-targeting PBMC-derived T cells and ability to proceed with T cell dose escalation
III Evaluate the safety profile of in-house manufactured MUC1-activated T cells in patients with relapsedrefractory MUC1-expressing ovarian cancer including all grades of neurotoxicity immune effector cell associated neurotoxicity ICANS and cytokine release syndrome CRS as determined by American Society for Transplantation and Cellular Therapy ASTCT criteria Lee 2018
IV Evaluate the preliminary efficacy of MUC1 T cells in patients that have received bridging therapy compared to those that did not receive bridging therapy
CORRELATIVE OBJECTIVES
I Determine whether culture expansion generated T cell receptor TCR oligoclonality through TCR Vbeta Analyses whether such T cells persist in the circulation following adoptive transfer and whether such persistence significantly correlates to objective responses
II Determine whether MUC1-activated T cells results in systemic inflammatory signaling by characterizing the changes in serum cytokine levels over time
III Determine whether T cells recognizing MUC1 in an MHC-restricted manner in culture intracellular IFN-γ assays enzyme-linked immunosorbent spot assay ELISpot correspond to therapeutic efficacy upon subsequent adoptive transfer
IV Determine the immunophenotype of the pre-infusion cell product day 0 and day 19 assessing cellular differentiation activation effector molecules and exhaustion markers and assess whether any parameters correlate with objective responses
V Determine the cytokine production at a single-cell level of the pre-infusion cell product day 0 and day 19
VI Evaluate the immunophenotype of diagnostic tumor material post-T cell infusion biopsy material post-relapse tumor material and ascites when available
VII Determine whether MUC1-activated T cell infusion is associated with changes in peripheral blood immune cell subsets
VIII Assess hospital resource utilization and health economics VIIIa Total number of hospitalizations intensive care unit ICU admissions and length of stay in hospital and ICU time between cell collection and infusion and total cost of product
OUTLINE This is a dose-escalation study
Patients undergo leukapheresis over 4 hours within 14 days after registration Patients receive cyclophosphamide intravenously IV over 60 minutes on days -5 to -3 or bendamustine IV over 10 minutes on days -5 and -4 or -4 and -3 Patients receive MUC1-activated T cells IV over 10-60 minutes on day 0 or days 0 and 21 Patients also undergo echocardiography ECHO or multigated acquisition scan MUGA during screening and blood sample collection throughout the trial In addition patients may undergo computed tomography CT magnetic resonance imaging MRI or positron emission tomography PETCT as clinically indicated throughout the trial Patients may also undergo collection of ascites on study and during follow up
Patients are followed up at 30 and 60 days from day 28 then every 3 months for 2 years
I To determine the maximum tolerated dose MTD of autologous MUC1-activated T-cells in-house manufactured MUC1-activated T cells in patients with relapsedrefractory MUC1-expressing ovarian cancer
SECONDARY OBJECTIVES
I Obtain preliminary efficacy associated with MUC1-targeting peripheral blood mononuclear cells PBMC-derived T cells in conjunction with cyclophosphamide CTX in MUC1-expressing ovarian cancer patients as measured by objective response rate best overall response of either partial response PR or complete response CR duration of response clinical benefit rate CR PR or stable disease SD time to disease progression progression free survival PFS and overall survival OS
II Determine feasibility of in-house production and administration of MUC1-targeting PBMC-derived T cells and ability to proceed with T cell dose escalation
III Evaluate the safety profile of in-house manufactured MUC1-activated T cells in patients with relapsedrefractory MUC1-expressing ovarian cancer including all grades of neurotoxicity immune effector cell associated neurotoxicity ICANS and cytokine release syndrome CRS as determined by American Society for Transplantation and Cellular Therapy ASTCT criteria Lee 2018
IV Evaluate the preliminary efficacy of MUC1 T cells in patients that have received bridging therapy compared to those that did not receive bridging therapy
CORRELATIVE OBJECTIVES
I Determine whether culture expansion generated T cell receptor TCR oligoclonality through TCR Vbeta Analyses whether such T cells persist in the circulation following adoptive transfer and whether such persistence significantly correlates to objective responses
II Determine whether MUC1-activated T cells results in systemic inflammatory signaling by characterizing the changes in serum cytokine levels over time
III Determine whether T cells recognizing MUC1 in an MHC-restricted manner in culture intracellular IFN-γ assays enzyme-linked immunosorbent spot assay ELISpot correspond to therapeutic efficacy upon subsequent adoptive transfer
IV Determine the immunophenotype of the pre-infusion cell product day 0 and day 19 assessing cellular differentiation activation effector molecules and exhaustion markers and assess whether any parameters correlate with objective responses
V Determine the cytokine production at a single-cell level of the pre-infusion cell product day 0 and day 19
VI Evaluate the immunophenotype of diagnostic tumor material post-T cell infusion biopsy material post-relapse tumor material and ascites when available
VII Determine whether MUC1-activated T cell infusion is associated with changes in peripheral blood immune cell subsets
VIII Assess hospital resource utilization and health economics VIIIa Total number of hospitalizations intensive care unit ICU admissions and length of stay in hospital and ICU time between cell collection and infusion and total cost of product
OUTLINE This is a dose-escalation study
Patients undergo leukapheresis over 4 hours within 14 days after registration Patients receive cyclophosphamide intravenously IV over 60 minutes on days -5 to -3 or bendamustine IV over 10 minutes on days -5 and -4 or -4 and -3 Patients receive MUC1-activated T cells IV over 10-60 minutes on day 0 or days 0 and 21 Patients also undergo echocardiography ECHO or multigated acquisition scan MUGA during screening and blood sample collection throughout the trial In addition patients may undergo computed tomography CT magnetic resonance imaging MRI or positron emission tomography PETCT as clinically indicated throughout the trial Patients may also undergo collection of ascites on study and during follow up
Patients are followed up at 30 and 60 days from day 28 then every 3 months for 2 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?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| MC220602 | OTHER | None | None |
| HT9425-24-1-0232 | OTHER_GRANT | None | None |
| NCI-2024-05158 | REGISTRY | None | None |
| 24-002437 | OTHER | None | None |
| CDMRP-OC230401 | OTHER_GRANT | None | None |