Gene-Modified T Cells With or Without Decitabine in Treating Patients With Advanced Malignancies Expressing NY-ESO-1
A Phase I/IIa Study of TGFß Blockade in TCR-Engineered T-Cell Cancer Immunotherapy in Patients With Advanced Malignancies
4 other identifiers
interventional
15
1 country
1
Brief Summary
This phase I/IIa trial studies the side effects and best dose of gene-modified T cells when given with or without decitabine, and to see how well they work in treating patients with malignancies expressing cancer-testis antigens 1 (NY-ESO-1) gene that have spread to other places in the body (advanced). A T cell is a type of immune cell that can recognize and kill abnormal cells of the body. Placing a modified gene for NY-ESO-1 into the patients' T cells in the laboratory and then giving them back to the patient may help the body build an immune response to kill tumor cells that express NY-ESO-1. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving gene-modified T cells with or without decitabine works better in treating patients with malignancies expressing NY-ESO-1.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jul 2017
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 21, 2015
CompletedFirst Posted
Study publicly available on registry
January 8, 2016
CompletedStudy Start
First participant enrolled
July 14, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 4, 2021
CompletedResults Posted
Study results publicly available
May 31, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
July 14, 2032
ExpectedJune 17, 2025
June 1, 2025
3.6 years
December 21, 2015
May 4, 2022
June 12, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Participants With Dose Limiting Toxicities
Will be assessed using Common Toxicity Criteria. Patients will be monitored by medical histories, physical examinations, ophthalmologic exams, and blood studies to detect potential toxicities from the treatment. the number of patients experiencing a DLT are reported.
Up to 30 days
Number of Participants With Feasibility Concerns in Manufacturing of NY-ESO-1/ dnTGFbetaRII Engineered Cells
Unfeasibility will be defined as 3 or more preparations not meeting the lot release criteria in each cohort. Sufficient numbers of circulating, lot released confirmed T cells will be measured prior to administration. The count of patients not meeting the preparation criteria are reported.
1 month
Secondary Outcomes (3)
Expression of the NY-ESO-1 T Cell Receptor (TCR) Transgenic Protein in Peripheral Blood Mononuclear Cells (PBMC)
Up to 15 years
Replication Competent Retrovirus (RCR)
Up to 1 year
Tumor Response (Complete and Partial Response)
Up to 90 days after TCR transgenic PBMC adoptive transfer
Study Arms (2)
Cohort I (cyclophosphamide, TCR/dnTGFbetaRII)
EXPERIMENTALPatients undergo leukapheresis on day -6 and receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients then receive TGFbDNRII-transduced autologous tumor infiltrating lymphocytes IV over 15 minutes on day 0. Eligible patients who showed initial response/disease control, may receive a second TGFbDNRII-transduced autologous tumor infiltrating lymphocytes infusion at any time after progression is confirmed.
Cohort II (decitabine, cyclophosphamide, TCR/dnTGFbetaRII)
EXPERIMENTALPatients undergo leukapheresis on day -6 and receive decitabine IV over 1 hour on days -6 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients then receive TGFbDNRII-transduced autologous tumor infiltrating lymphocytes IV over 15 minutes on day 0. Eligible patients who showed initial response/disease control, may receive a second TGFbDNRII-transduced autologous tumor infiltrating lymphocytes infusion at any time after progression is confirmed.
Interventions
Given IV
Given IV
Correlative studies
Undergo leukapheresis
Given IV
Eligibility Criteria
You may qualify if:
- Patients with solid tumors as described below:
- Inoperable or metastatic (advanced) melanoma:
- Has received, is intolerant, or refused a CTLA-4 inhibitor (ipilimumab) or a PD-1 inhibitor (nivolumab or pembrolizumab) as monotherapy and/or a combination of ipilimumab and nivolumab
- Has received or is intolerant of a BRAF inhibitor or the combination of BRAF and MEK inhibitors for BRAFv600 mutant melanoma and a PD-1 inhibitor as monotherapy or in combination
- Inoperable or metastatic (advanced) ovarian, primary peritoneal or fallopian tube carcinoma:
- Has received platinum containing chemotherapy and has platinum refractory or resistant disease that has progressed on second line therapy
- If platinum sensitive disease, should have received \>= 2 lines of chemotherapy
- May have received PARP inhibitors, bevacizumab or other targeted VEGF inhibitor therapy
- Inoperable or metastatic (advanced) synovial sarcoma:
- Should have received and progressed on \>= two lines of systemic therapy
- Subjects with other histologies:
- Must have previously received two lines of systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been deemed either non-responders (progressive disease) or have recurred
- For cohorts 1, 2 and 3 only: Patient's tumor must be positive by histological or molecular assay for NY-ESO-1, according to the screening algorithm; historical results may be used
- For cohort 4, NY-ESO-1 results will be noted but NY-ESO-1 positivity is not required for eligibility
- Human leukocyte antigen (HLA)-A\*0201 (HLA-A2.1) positivity by molecular subtyping (blood test or buccal swab, historical documentation acceptable)
- +26 more criteria
You may not qualify if:
- Previously known hypersensitivity to any of the agents used in this study
- Currently receiving any other investigational agents. Note: Patients who have suffered \>grade 2 irAEs during previous checkpoint inhibitor therapy should be excluded.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; electrocardiogram (EKG) will be done at screening; cardiac stress test will be done as clinically indicated, the specific test to be chosen at the discretion of the treating physician.
- History of severe autoimmune disease requiring steroids or other immunosuppressive treatments
- History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding, which in the investigator's opinion would place the patient at an increased risk for adverse effect or current acute colitis of any origin; treated cases with no active disease are eligible
- Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 4 weeks prior to enrollment (inhaled or topical steroids at standard doses or isolated use of steroids as premedication for medical procedures to minimize allergic reaction \[e.g. computed tomography (CT) scan dye\] are allowed)
- Known active infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis C or cytomegalovirus (CMV)
- Dementia or significantly altered mental status that would prohibit the understanding or rendering of compliance with the requirements of this protocol even with caregiver support
- Pregnancy or breast-feeding; female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and 6 months after; all female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 48 hours from starting the conditioning chemotherapy
- Lack of availability of a patient for immunological and clinical follow-up assessment
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Roswell Park Cancer Institutelead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Kris Attwood
- Organization
- Roswell Park Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Philip McCarthy, MD
Roswell Park Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 21, 2015
First Posted
January 8, 2016
Study Start
July 14, 2017
Primary Completion
March 4, 2021
Study Completion (Estimated)
July 14, 2032
Last Updated
June 17, 2025
Results First Posted
May 31, 2022
Record last verified: 2025-06