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

NCT ID: NCT06483048

Condition: Platinum-Resistant Fallopian Tube Carcinoma
Platinum-Resistant Ovarian Carcinoma
Platinum-Resistant Primary Peritoneal Carcinoma
Recurrent Fallopian Tube Carcinoma
Recurrent Fallopian Tube Carcinosarcoma
Recurrent Female Reproductive System Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Ovarian Carcinosarcoma
Recurrent Platinum-Resistant Fallopian Tube Carcinoma
Recurrent Platinum-Resistant Ovarian Carcinoma
Recurrent Primary Peritoneal Carcinoma
Recurrent Primary Peritoneal Carcinosarcoma
Refractory Fallopian Tube Carcinoma
Refractory Female Reproductive System Carcinoma
Refractory Ovarian Carcinoma
Refractory Primary Peritoneal Carcinoma

Conditions: Official terms:
Carcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Carcinosarcoma
Mixed Tumor, Mullerian
Recurrence
Cyclophosphamide
Bendamustine Hydrochloride

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: Autologous MUC1-activated T-cells
Description: Given IV
Arm group label: Treatment (MUC1-activated T cells, lymphodepletion)

Other name: Autologous MUC1-activated T-lymphocytes

Intervention type: Drug
Intervention name: Bendamustine
Description: Given IV
Arm group label: Treatment (MUC1-activated T cells, lymphodepletion)

Other name: SDX-105

Intervention type: Procedure
Intervention name: Biospecimen Collection
Description: Undergo blood and possible ascites sample collection
Arm group label: Treatment (MUC1-activated T cells, lymphodepletion)

Other name: Biological Sample Collection

Other name: Biospecimen Collected

Other name: Specimen Collection

Intervention type: Procedure
Intervention name: Computed Tomography
Description: Undergo CT or PET/CT
Arm group label: Treatment (MUC1-activated T cells, lymphodepletion)

Other name: CAT

Other name: CAT Scan

Other name: Computed Axial Tomography

Other name: Computerized Axial Tomography

Other name: Computerized axial tomography (procedure)

Other name: Computerized Tomography

Other name: Computerized Tomography (CT) scan

Other name: CT

Other name: CT Scan

Other name: tomography

Intervention type: Drug
Intervention name: Cyclophosphamide
Description: Given IV
Arm group label: Treatment (MUC1-activated T cells, lymphodepletion)

Other name: (-)-Cyclophosphamide

Other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate

Other name: Asta B 518

Other name: B-518

Other name: Carloxan

Other name: Ciclofosfamida

Other name: Ciclofosfamide

Other name: Cicloxal

Other name: Clafen

Other name: Claphene

Other name: CP monohydrate

Other name: CTX

Other name: CYCLO-cell

Other name: Cycloblastin

Other name: Cycloblastine

Other name: Cyclophospham

Other name: Cyclophosphamid monohydrate

Other name: Cyclophosphamide Monohydrate

Other name: Cyclophosphamidum

Other name: Cyclophosphan

Other name: Cyclophosphane

Other name: Cyclophosphanum

Other name: Cyclostin

Other name: Cyclostine

Other name: Cytophosphan

Other name: Cytophosphane

Other name: Cytoxan

Other name: Fosfaseron

Other name: Genoxal

Other name: Genuxal

Other name: Ledoxina

Other name: Mitoxan

Other name: Neosar

Other name: Revimmune

Other name: Syklofosfamid

Other name: WR- 138719

Other name: WR-138719

Intervention type: Procedure
Intervention name: Echocardiography
Description: Undergo ECHO
Arm group label: Treatment (MUC1-activated T cells, lymphodepletion)

Other name: EC

Intervention type: Procedure
Intervention name: Leukapheresis
Description: Undergo leukapheresis
Arm group label: Treatment (MUC1-activated T cells, lymphodepletion)

Other name: Leukocytopheresis

Other name: Therapeutic Leukopheresis

Intervention type: Procedure
Intervention name: Magnetic Resonance Imaging
Description: Undergo MRI
Arm group label: Treatment (MUC1-activated T cells, lymphodepletion)

Other name: Magnetic Resonance

Other name: Magnetic Resonance Imaging (MRI)

Other name: Magnetic resonance imaging (procedure)

Other name: Magnetic Resonance Imaging Scan

Other name: Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

Other name: MR

Other name: MR Imaging

Other name: MRI

Other name: MRI Scan

Other name: MRIs

Other name: NMR Imaging

Other name: NMRI

Other name: Nuclear Magnetic Resonance Imaging

Other name: sMRI

Other name: Structural MRI

Intervention type: Procedure
Intervention name: Multigated Acquisition Scan
Description: Undergo MUGA
Arm group label: Treatment (MUC1-activated T cells, lymphodepletion)

Other name: Blood Pool Scan

Other name: Equilibrium Radionuclide Angiography

Other name: Gated Blood Pool Imaging

Other name: Gated Heart Pool Scan

Other name: MUGA

Other name: MUGA Scan

Other name: Multi-Gated Acquisition Scan

Other name: Radionuclide Ventriculogram Scan

Other name: Radionuclide Ventriculography

Other name: RNVG

Other name: SYMA Scanning

Other name: Synchronized Multigated Acquisition Scanning

Intervention type: Procedure
Intervention name: Positron Emission Tomography
Description: Undergo PET/CT
Arm group label: Treatment (MUC1-activated T cells, lymphodepletion)

Other name: Medical Imaging, Positron Emission Tomography

Other name: PET

Other name: PET Scan

Other name: Positron emission tomography (procedure)

Other name: Positron Emission Tomography Scan

Other name: Positron-Emission Tomography

Other name: proton magnetic resonance spectroscopic imaging

Other name: PT

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 body's 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 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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - PRE-REGISTRATION: Age ≥ 18 years - PRE-REGISTRATION: Diagnosis or history of epithelial ovarian, fallopian tube, carcinosarcoma, or primary peritoneal cancer - PRE-REGISTRATION: Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria on study entry, which must include at least 1 lesion that has a single diameter of ≥ 1 cm measured by CT or MRI or the CT portion of the PET/CT - Skin lesions can be used if the area is ≥ 1cm in at least one diameter and measured with a ruler - PRE-REGISTRATION: Relapsed or refractory ovarian cancer previously treated with or intolerant to at least one prior line of therapy with platinum chemotherapy and be relapsed or have tumor evaluable for response if in first line setting resistant or ineligible to platinum. Patients with BRCA1/2 mutations must have received prior treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor to be eligible. Platinum-resistance is defined as any of the following occurring < 183 days after the last dose of platinum-based chemotherapy: - Development of measurable disease (per RECIST 1.1) - Progression of radiographic disease (per RECIST 1.1) - Increase in CA-125 level to ≥ 2 x upper limit of normal (ULN) (if within normal limits [WNL] at the completion of platinum-based chemotherapy) - Increase in CA-125 level to ≥ 2 x nadir (if nadir > ULN) - If CA-125 is used to determine the date of progression then it must be confirmed by a second CA-125 value ≥ 7 days after the first level and concurrent with imaging changes. The date of the first qualifying CA-125 is used to compute the platinum-free interval - PRE-REGISTRATION: Provide written informed consent - PRE-REGISTRATION: Willingness to provide mandatory blood specimens and biopsy tissue for correlative research - REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 - REGISTRATION: Histologically confirmed surgical diagnosis of epithelial ovarian, fallopian tube, carcinosarcoma, or primary peritoneal cancer with measurable disease. NOTE: Histologic confirmation of the primary tumor is required. Eligible histologies include serous, endometrioid, clear cell, mucinous, transitional cell, undifferentiated, or mixed carcinoma - REGISTRATION: MUC1 expression in ovarian cancer tumor cells verified by immunohistochemistry (IHC) in a Clinical Laboratory Improvement Act (CLIA) laboratory. Heterogeneous tumor expression of MUC1 is acceptable. MUC1 expression by staining score greater than 0 is deemed positive for this study - REGISTRATION: Expected survival unless investigational therapy is effective is greater than 6 months but less than 24 months - REGISTRATION: Willingness and ability to provide written informed consent - REGISTRATION: Willing to return to Mayo Clinic in Arizona (MCA) for follow-up during the active monitoring phase of the study - REGISTRATION: Willing to undergo leukapheresis for blood component collection - REGISTRATION: Absolute neutrophil count (ANC) ≥ 1500/mm^3 (performed ≤ 14 days prior to registration) - REGISTRATION: Lymphocyte count ≥ 1500/mm^3 (performed ≤ 14 days prior to registration) - REGISTRATION: Hemoglobin ≥ 8.0 g/dL (performed ≤ 14 days prior to registration) - REGISTRATION: Platelet count ≥ 30,000/mm^3 (performed ≤ 14 days prior to registration) - REGISTRATION: Total bilirubin ≤ 2.0 mg/dL unless patient has documented Gilbert's syndrome (subjects with Gilbert's syndrome may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN) (performed ≤ 14 days prior to registration) - Alanine aminotransferase (ALT) and aspartate amino transferase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer) (performed ≤ 14 days prior to registration) - REGISTRATION: Prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulation therapy and INR or aPTT is within target range of therapy (for patients receiving anticoagulation, there should be no prior history of bleeding and no recent deep vein thrombosis [DVT]/pulmonary embolism [PE] ≤ 6 months prior to registration) (performed ≤ 14 days prior to registration) - REGISTRATION: Calculated creatinine clearance ≥ 30 ml/min using the Cockcroft-Gault formula (performed ≤ 14 days prior to registration) - REGISTRATION: Baseline oxygen saturation ≥ 90% on room air - REGISTRATION: Negative urine or serological pregnancy test ≤ 7 days prior to registration Exclusion Criteria: - Clinically unresolved central nervous system (CNS) metastases. NOTE: Patients with a prior history of brain metastases are allowed if focally treated, radiographically stable for > 30 days, and not requiring steroid therapy for > 14 days - Prior treatment targeting MUC1 - Subjects with known plasma cell leukemia (PCL) - Any of the following are excluded because this study involves an agent (CTX) that has known genotoxic, mutagenic and/or teratogenic effects: - Pregnant persons - Nursing persons - Persons of childbearing potential who are unwilling to employ adequate birth control measures - History of myocardial infarction ≤ 6 months prior to registration, and/or congestive heart failure requiring ongoing treatment such as medications and/or an implanted defibrillator to control life-threatening arrhythmias - Failure to recover to grade 1 or baseline from acute, reversible effects of prior therapy regardless of interval since last treatment. EXCEPTION: Grade 2 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment. - Uncontrolled concurrent illness including, but not limited to: - Inability to clear an ongoing or active infection - Symptomatic congestive heart failure - Unstable angina pectoris - Uncontrolled psychiatric problems - Inability to have a caregiver for active oversight during treatment period - Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy - Any other conditions that the protocol investigators deem could potentially limit compliance with study requirements - Evidence of clinical immunocompromise and/or HIV positivity and currently receiving antiretroviral therapy - Patients requiring chronic supraphysiologic daily doses of steroids (> 10 mg prednisone or prednisolone, ≥ 4 mg Decadron or ≥ 50 mg hydrocortisol daily) - Patients receiving any other investigational agent which could be considered a treatment for the neoplasm - Other active malignancy first documented ≤ 4 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history of other malignancy, the patient must not be receiving other treatment aimed at suppressing its recurrence - Diagnosis of autoimmune disease - Known history of active autoimmune disease that has required systemic treatment in the ≤ 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-registration. NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves' disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded

Gender: Female

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Mayo Clinic in Arizona

Address:
City: Scottsdale
Zip: 85259
Country: United States

Status: Recruiting

Contact:
Last name: Clinical Trials Referral Office

Phone: 855-776-0015
Email: mayocliniccancerstudies@mayo.edu

Contact backup:
Last name: Brenda J. Ernst, MD

Start date: September 20, 2024

Completion date: September 30, 2028

Lead sponsor:
Agency: Mayo Clinic
Agency class: Other

Source: Mayo Clinic

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06483048
https://www.mayo.edu/research/clinical-trials

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