MUC1-Activated T Cells for the Treatment of Relapsed and Resistant Ovarian Cancer

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 relapsed/refractory 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 relapsed/refractory 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 (PET)/CT 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.