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
